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ABSTRACT
Year : 2016  |  Volume : 7  |  Issue : 5  |  Page : 1-32

1st Annual Saudi Blood Disorders Research Meeting


Date of Web Publication16-Jun-2016

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How to cite this article:
. 1st Annual Saudi Blood Disorders Research Meeting. J Appl Hematol 2016;7, Suppl S1:1-32

How to cite this URL:
. 1st Annual Saudi Blood Disorders Research Meeting. J Appl Hematol [serial online] 2016 [cited 2019 May 22];7, Suppl S1:1-32. Available from: http://www.jahjournal.org/text.asp?2016/7/5/1/184226

A-001: A prospective cohort study: Prevalence of platelet transfusion refractoriness among patients with haematological malignancies in a Tertiary Center in Saudi Arabia

Munira A. AlKhashan 1 , Atheer AlOtaibi 1 , Salwa AlRashed AlHumaid 1 , Khadega Ahmed 1,2

1 King Saud Bin Abdulaziz University, For Health Sciences, Al Hars Al Watani, Ar Rimayah, Riyadh 14611, 2 Department of Oncology, King Abdulaziz Medical City, Jeddah, Saudi Arabia

Background and Purpose: Oncohematologic patients require chemotherapy; therefore they are at risk of developing severe thrombocytopenia. In order to treat severe thrombocytopenia, platelet transfusions are inevitable. Platelet transfusion refractory is defined as "lack of response in post transfusion platelet increments after transfusion of an adequate dose of allogeneic platelets which leads to shortened survival of the transfused platelets in the recipient's circulation." We studied the prevalence of platelet transfusion refractoriness in adult hematology oncology and stem cell transplanted patients at King Abdul-Aziz Medical City (KAMC), Riyadh. Methods: This was a prospective cohort study. After obtaining informed consents, multiple platelet counts were collected from each subject at baseline and one hour after different platelet transfusion events. Then, the corrected count increment (CCI) was calculated to evaluate the response by using the following formula: CCI = [(A-B) × BS]/C ×10 11 A: platelet count one-hour post transfusion. B: is pretransfusion platelet count. BS: is the body surface area. C: is the total number of transfused platelets. Medical records also were reviewed for demographical and clinical data. Results and Discussion: A total of 29 patients were recruited. Platelet transfusion refractoriness was found in 17 out of 102 events. We found no significant correlation between age, gender, history of stem cell transplant and number of exposure to blood products. The prevalence of platelet refractoriness observed in this study (16.7%) was similar to that reported in international literature. We found an association between the type of cancer and the prevalence of platelet refractoriness. Our data suggest an association between platelet refractoriness and Acute Myeloid Leukemia (AML) and non-Hodgkin's lymphoma. Conclusion and Recommendations: The prevalence of platelet refractoriness in Saudi hematology malignancies is similar to what was reported internationally. We recommend that a larger sample size be studied to further elaborate on the prevalence and correlate different demographical and clinical factors that may be associated with platelet transfusion refractoriness.

A-002: Incidence of venous thromboembolism and related mortality among cancer patients in Tertiary Care Hospital

Ahmed S. Ali, Adel Hamodi 1 , Hamdi Saudi 2 , Walid Selwi 3

Departments of Adult Medical Oncology, 1 ICU, 2 Oncology Clinical Pharmacy and 3 Adult Medical Oncology, King Fahad Specialist Hospital, Dammam, Saudi Arabia

Background: Correlation between thromboembolic events and malignancy is a renowned phenomenon. The incidence of such devastating events in vulnerable oncology patients dictates further studies in cancer centers. Effect of the disease stage, chemotherapy received, performance status, and other demographic data are observed as well. Methods: In a retrospective analysis, the incidence of deep vein thrombosis, and/or pulmonary embolism have been studied in cancer patients admitted to the adult medical oncology department during the period of 2013 and 2014, the effect of the stage of the disease, chemotherapy or hormonal therapy received, ECOG performance status, and use of prophylactic anticoagulants have been studied, along with the incidence of side effects with the use of anticoagulants and the consequences (mortality and morbidity) caused by these events. Results: A retrospective review of the electronic data base was conducted to include analysis of an enormous amount of data belongs to 2286 patients treated in the Cancer Center at King Fahad specialist Hospital between January 2013 to December 2014. This study analyzed the data of 144 oncology patients who as diagnosed to have VTE which constitutes 6.3% of total oncology center admissions. The mean age of the studied group was 53.2 years (SD = 14.7 years) with insignificant difference between male and female distribution being 76 and 68 respectively. Pulmonary embolism was documented in 39% while 61.8% had DVT. Fifty two percent (52%) of the patients had distant metastasis. The mortality during the study period was about 31.8% in patient with VTE. Conclusion: The need for prophylactic enoxaparine should be tailored according to the risk for developing thromboembolic complications in cancer patients; the risk is higher in patients with advanced carcinoma stages, poor ECOG performance status, and GIT adenocarcinoma.

A-003: Analysis of heparin induced thrombocytopenia screening tests in critical care units at King Faisal specialized Hospital and Research Center

S. Barri, M. G. Jamil, O. Khojah, K. Maghrabi, N. Salahuddin, R. Amin, T. Owaidah

Department of Pathology and Laboratory Medicine and Critical Care, King Faisal Specialist Hospital and Research Centre, Al Maather, Riyadh 12713, Saudi Arabia

Background and Purpose: Heparin induced thrombocytopenia (HIT) is a consequence of atypical immunological response resulting in IgG antibodies against platelet factor 4 (PF4) which cross-links with Fcg receptor 2a on platelet leading to significant drop in platelet count. Instead of bleeding, this phenomenon leads frequently and paradoxically to thrombotic event by platelet activation. It is estimated 1 in 5000 hospitalized patients and 1 in 0.1-0.5% individuals exposed to heparin developed HIT, especially when administration of unfractionated heparin (UH) comparing with low molecular weight heparin (LMWH). Recent publications have shown inconsistency in increased HIT incidence among critically ill individuals. This study estimated the HIT burden in our intensive care unit (ICU) in relation to whole institute and international figures. Methodology: A retrospective observational study reviewed 1,238 HIT screening tests for patients receiving UH and/or LMWH with clinical suspicion of HIT by two screening methods from 2011 to 2014. The two methods were validated and accredited by College of American Pathologist (CAP) The diamed rapid particle gel Immunoassay (Di-PaGIA) and enzyme linked immunosorbent assay (ELISA) screening methods were used to identify and semi-quantify Heparin/PF4 antibody complex. Results: There were 340 tested samples from patients in ICU with age ranging from 1 week to 111 years (median, 62 years). Out of those samples, 12.94% were positive by one or both used methods. In this cohort, 232 patients were exposed to UH, 31 to LMWH and 77 to both medications. The tests reported positive for HIT 16.81% in patients exposed to UH and 6.49% for patients who received both medications and none tested positive for those who received LMWH alone. The reported prevalence of HIT positivity in all requested tests (1,238) was 7.35%. Excluding the ICU patients, 47 (5.23%) out of 898 requests from general hospital' wards were positive. The expected number of patients needed to develop one event of HIT is approximately 470 individuals as 43,123 individuals were exposed to heparin during study period. In sub-grouping analysis, the estimated number needed to develop HIT is 3,360 treated patients when administration of LMWH alone. Conclusion: These results are in concordance with what has been reported as an increase incidence of HIT among critically ill patients. UH clearly is more associated with developing HIT when compared with LMWH administration. This could be used as a surrogate indicator for quality assurance in HIT awareness among ICU physicians. Further large scale prospective study is needed to confirm these observations.

A-004: Nineteen β-thalassemia mutations of Saudi patients with a five rare mutations, single institution experience

Ayman Mashi, Adnan Khyatte, Hala Abalkhail, Salem Khalil

King Fahad Central Hospital, Ministry of Health, Jazan, 1 Department of Pathology, Hematology Section, King Khalid University Hospital, 2 Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Background: Beta thalassemias (β thalassemia) are a group of hereditary disorders that are caused by reduced or absent synthesis of the beta chains of hemoglobin due to mutations affecting critical areas of the beta-globin gene on chromosome 11. The disease is inherited in an autosomal recessive manner, with severity ranging from asymptomatic individuals to transfusion dependent anemia according to the nature of the mutation. The prevalence of the β-globin gene in various areas of Saudi Arabia previously reported as 0.01-0.15% in general population. Methods: A cohort of 131 samples submitted for beta-globin gene mutation analysis during 2008-2013 were tested for the entire genomic region (3-Exons and 2-Introns) of the HBB gene by direct Sanger sequencing technique. Results: Out of the total population tested, 28 (21%) were undetectable cases and 103 (79%) were detectable for beta globin chain mutations. Nineteen different mutations of the HBB gene were identified in all detectable cases (103 patients). Among of these mutations c.315+1G>A, c.118C>T and c.92+5G>C were detect in majority of cases (66%) with five mutations (c.410G>A, c.-151C>T, c.68_74delAAGTTGG, c.316-3C>A, and c.-31C>T) are first time reported in Saudi population. Discussion: The result of this retrospective study confirms the previously reported common Beta thalassemia mutations among Saudi population.

A-005: Next generation sequencing "hematology" gene panel based mutation spectrum and clinical implications in Saudi patients with Fanconi anemia

Majed Dasouki 1,2 , Syed Osman Ahmed 3 , Ali Alahmari 3 , Amal Jabr 1 , Moheeb Ali Alawwami 4 , Naeem A. Chaudhri 3 , AlMohareb Fahad 3 , Said Y. Mohamed, 3 Walid Rasheed 3 , Hazza A. Alzahrani 3 , Mahmoud Aljurf 3

1 Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, 3 King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, 4 Histocompatibility and Immunogenetics Laboratory, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, 2 Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA

Background: Fanconi anemia (FA) is a well-recognized autosomal recessive progressive bone marrow failure syndrome with characteristic clinical findings including congenital anomalies, failure to thrive, developmental delays, abnormal chromosome breakage as well as increased incidence of hematologic and non-hematologic malignancies. However, a significant number of patients with FA do not exhibit the typical clinical features and will escape early diagnosis. Especially in such individuals, next generation sequencing (NGS) based diagnosis may lead to an early and definitive diagnosis and consequently proper genetic counselling, cancer surveillance and personalized clinical management. Methods: We developed a comprehensive hematology "405" gene panel which includes all known Mendelian haematological disorders (hemolytic anemias, aplastic anemias/bone marrow failure syndromes, coagulation disorders) using the Ion Torrent-Proton based-AmpliSeq technology. We have so far analysed 170 samples of patients with acquired and/or inherited bone marrow failure syndromes. In 9 Saudi patients with Fanconi anemia and abnormal chromosome breakage, mutation analysis of their gDNA as well as cytogenetic analysis of their bone marrow was performed. Results: Chromosome breakage studies were abnormal in 8 and inconclusive in 1 patient. Following validation of the gene panel, homozygous mutations in six patients, 5 novel as well as one previously reported rare mutation [BRIP1 (2), SLX4 (2), FANCE (1) and FANCA (1)], were identified using the Ion Torrent "Proton" based sequencing followed by Sanger confirmation. Conclusion: The NGS based "Hematology" gene panel offers a rapid turnaround and high yield in Saudi patients with FA whose mutation spectrum differs from the literature. In particular, patients with mutations in the breast cancer gene BRCA1 interacting protein C-terminal helicase 1 (BRIP1, also known as FANCJ) as well as their first degree relatives should undergo tailored clinical surveillance, given its association with susceptibility to breast cancer.

A-006: Prevalence and characteristics of epistaxis in Saudi population

O. Al-Swailmi, O. Khojah, R. Al-Bakr, H. Al-Zahrani, A. Al-Zahrani, M. Al-Madani, A. Al-Suliman, K. Sidiqi, A. Al-Benian, T. Owaidah

Department of Pathology and Laboratory Medicine, Adult Hematology and Biostatistics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Background and Purpose: Nose bleeding is the commonest unspecified bleeding symptom across general population world-widely. It is also implicated as a main presentation in many bleeding diatheses. However, epistaxis occasionally needs a medical intervention. To date, there is no data that represents its burden in Saudi Arabia. This epidemiological study addresses detailed characteristics of epistaxis among young adults in our population. Methodology: This a cross-sectional study is a part of an ongoing national-wide project on bleeding disorders. It is based on validated questionnaire approved by the International Society of Thrombosis and Hemostasis (ISTH). The used questionnaire was applied and recognized in many scientific studies and organizations. It addressed all the clinically relevant bleeding symptoms in inclusive and detailed manners. This questionnaire was validated again after translation in Arabic and then total of 740 first-year undergraduate students in Riyadh were interviewed by qualified health-care providers. Results: Out of 740 participants (M:F is 1.9:1), 312 (42%) were reported a history of epistaxis (46%male, 36%female) with around 30% showing a significant nose bleeding in their lives. Bleeding was encountered more than once monthly in 8.8% and 22.5% bled for >1 min (2.4% for >10 min) and 17%, needed medical attention. Out of the 312 withepistaxis, 84%, 50% and 31% reported spontaneous bleeding, seasonal fluctuation, and epistaxis from both nostrils, respectively. Only 2 subjects were on oral anti-coagulant from individuals who reported a positive history of nose bleeding. Cessation of bleeding was achieved after local compression in 70% and spontaneously in 24%. Only 12% got medical consultation alone, 4% underwent cauterization and 1% reported packing as a medical intervention. No individual received blood transfusion as a consequence of severe epistaxis. Conclusion: This first regional study investigated the prevalence of epistaxis showed that epistaxis is a common bleeding symptom among young Saudis with slightly more prevalence in males. These findings encourage the authorities to implementation of educational program, first aid in particular, for initial management of epistaxis. Finally, a further correlation with laboratory results will refine these data and obtain better understanding of epistaxis role among our patients whom suffering from bleeding disorder.

A-007: Epidemiological characteristics of oral cavity bleeding in Saudis

N. Abu-Issa, H. Al-Zahrani, A. Al-Zahrani, M. Al-Madani, A. Al-Suliman, K. Sidiqi, A. Al-Benian, O. Khojah, T. Owaidah

Department of Pathology and Laboratory Medicine, Adult Hematology and Biostatistics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Background and Purpose: Bleeding disorders, including oral cavity bleeding, are prevalent in general population. Majority of these disorders manifests as chronic bleeding tendency or increase in bleeding time and amount during surgical procedure, after brushing or trauma. Baseline data about prevalence of oral cavity bleeding in Saudi Arabia is substantially unavailable. In addition, many international studies indicated different age groups experienced changes in frequency and causes of oral cavity bleeding. Therefore, this epidemiological study was conducted to identify the prevalence of bleeding symptoms in oral cavity among young adult Saudis. Methodology: This questionnaire-based study is a cross-sectional and part of an ongoing national-wide project on bleeding disorders. The 740 participants, from the foundation year in universities in Riyadh, were interviewed by a qualified health care provider and answered a detailed clinically relevant questions related to bleeding diathesis. This questionnaire was introduced by the International Society of Thrombosis and Hemostasis (ISTH) and used internationally in frequent epidemiological studies that evaluated bleeding disorders. Moreover, the questionnaire was validated locally by experts after translation to Arabic language. Results: In this ongoing study, the current results showed 486 participants being male and 254 being female with male to female ratio 1.9:1. Out of the 740 students, 354 (47.8%) participants reported positive history of oral cavity bleeding. In the male group, 206 students (42.4%) experienced an oral cavity bleeding comparing with 148 students (58.3%) in the female group. However, the majority (293/354, 82%) of these positive oral cavity bleeding history individuals reported that bleeding occurred in concurrent with brushing their teeth. A spontaneous gum bleeding, lips or tongue bleeding after gentile bite and bleeding from tooth eruption were reported in 24.9% (88/354), 9.3%(33/354) and 2.0% (7/354), respectively. Indeed, only 26 (7.3%) participants from whom reported a history of oral cavity bleeding endeavored a medical attention, mainly for consultation. One participant only required a blood transfusion. Conclusion: This study revealed a high prevalence of oral cavity bleeding in adolescent and young adult Saudis. In fact, the majority of such bleeding might be prevented and effectively controlled by feasible parameters. One of the major solution is community awareness with routine patient education concerning periodontal disease. These programs likely will improve the oral health of general community and control this global problem. Finally, severe cases that required medical interventions need to be investigated thoroughly for underling bleeding diathesis.

A-008: Phenotypic and molecular studies of 25 glanzmann thrombasthenia Saudi patients resulting in identification of five novel mutations

O. Khojah, S. Berri, N. Al-Tassan, R. Al-Nounou, H. Al-Zahrani, M. Saleh, A. Al-Mosa, H. Aba Alkhail, A. Al-Benian, T. Owaidah

Department of Pathology and Laboratory Medicine, Hematology, Pediatric Oncology and Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Background and Purpose: Glanzmann thrombasthenia (GT) is a rare autosomal recessive congenital bleeding disorder with prevalence of 1:1,000,000 that characterized by platelet aggregation dysfunction with significant susceptibility of prolonged bleeding even with minor injury. Abnormality in glycoprotein 2b (ITGA2B gene/CD41/GPIIb) or glycoprotein 3a (ITGB3 gene/CD61/GPIIIa) results in developing classical GT disease. Currently, the international GT database includes 419 GT patients with 255 and 164 patients showing abnormalities in ITGA2B and ITGB3, respectively. Almost 100 mutations have been reported with no molecular data from Saudi Arabia. This fundamental study unveils the molecular basis of GT in Saudi registry. Methodology: Out of 59 cases in GT Saudi registry, 25 patients were successfully enrolled in ongoing Saudi Genome Project. In addition, 12 participants were also enrolled in this study with a majority of them being a first-degree relative of the 25 GT patients. The phenotypic diagnosis of the GT was based on clinical presentation, platelet function tests including PFA-100 and multi-plate platelet aggregometry and platelet glycoprotein expression by flow cytometry. The result of the whole-exome sequencing of ITGA2B and ITGB3 genes were retrieved and examined thoroughly to identify any potential mutation using Heme-Chip by next generation sequencing (NGS) which had a coverage of 120 reads in average (ranging 60-170). Results: There were 37 participants in this study from 14 different Saudi families with 25 participants being diagnosed as GT (13 females and 12 males) based on conventional laboratory studies. The overall concordance rate between the classical studies result and molecular analysis is 87%, 32 out of 37 cases. Molecular testing identified five different hits in ITGA2B and two others in ITGB3. Out of 37 sequenced patients, 14 cases (12 homozygous, 2 heterozygous) revealed a mutation in ITGA2B and ITGB3 was mutated in 14 cases (8 homozygous, 6 heterozygous). However, 5 (20%) GT patients showed normal sequencing of both genes which might represent GT variant cases. Interestingly, three novel mutations were identified in ITGA2B gene (c.1210+5G>A, p.L539R and c.1879-2A>G) and the both identified mutations in ITGB3 (p.D243H and p.I704fs) were also not reported before. Applying a deleterious effect model in novel mutations upon protein structure showed an adverse result on protein assembly that correlated with flow cytometry analysis of platelet glycoprotein expression [Table 1]. Conclusion: This is the first report of molecular genotype of GT in Saudi Arabia with identification of five novel mutations. These mutations likely cause GT and might have an impact on the disease phenotype. This in particular needs to be correlated with clinical and laboratory findings, gene and protein expression studies and further epidemiological and experimental models. Finally, other responsible genes should be investigated for GT variant-cases.



A-009: Improved outcome of patients with early use of rituximab in patients with thrombotic thrombocytopenic purpura at King Fahad Medical City, Riyadh

Shahid Iqbal, Imran Tailor, Syed Zaidi, Ibraheem Motabi, Nawal Al-Shehry, May Al-Moshary 1 , Assem El-Ghazaly, Samer Al-mudaibegh, Gulam Murtaza, Taimoor Hussain

Departments of Adult Hematology/BMT and 1 Hematopathology/Transfusion Medicine Service/Blood Bank, King Fahad Medical City, Riyadh, Saudi Arabia

Background: Adult onset acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease mediated by autoantibodies directed against ADAMTS13. Therapeutic plasma exchange (TPE) and immunosuppressive therapies have largely remained the mainstay of treatment. Several studies have reported promising results with early use of rituximab. Rituximab is a safe and effective treatment for newly diagnosed TTP, and has shown in a prospective, multicenter trial to decrease the number of plasma exchanges (PEX) required to achieve remission, to decrease the length of inpatient stay and to reduce the risk of relapse by over 80% when compared to historical controls. Aims: We report our experience with early use of rituximab in patients with initial severe manifestations (cardiac or neurological involvement) or those who were failing to show early response to TPE from a tertiary care center in Saudi Arabia. Methods: This is retrospective data of ten patients with TTP who received rituximab either for refractory disease or sever manifestations of TTP since 2006-2014 at our tertiary care hospital, Saudi Arabia. Results: Total of ten patients with TTP received rituximab either for refractory disease or sever manifestations of TTP since 2006-2014. There were six females (60%) and four males (40%). The median age was 33 ± 12.08. Nine of the ten patients (90%) had neurological involvement ranging from headache, dizziness, confusion, seizures and focal neurological signs. Four patients (40%) had renal impairment. Two patients (20%) had associated systemic lupus erythematosus (SLE). Five patients (50%) were refractory to plasma exchange while the rest received early rituximab due to cardiac or neurological involvement at treating physician's discretion. Four patients received Rituximab within 5 days of diagnosis. Seven patients received weekly four doses of Rituximab at 375 mg/m 2 while two patients received eight and five doses weekly. One patient with SLE received two doses at 1000 mg each as per rheumatology protocol for the benefit of treatment of concurrent SLE. Nine out of ten (90%) achieved complete response; no subsequent relapses occurred with median follow-up of 16 months (range, 6-62 months). There was one death during the early course of disease due to delayed presentation. Number of mean plasma exchanges in early rituximab group who received Rituximab within five days was 13.5 while it was 17.4 in those who received later than day 5. Number of mean total plasma volumes exchanged in early Rituximab group were 11.1 (range 7.8-15.5) compared to 16.15 in later group (range 11.2-25.2). There were no serious immediate complications noted. On longer term clinical follow up, we have not found any increased tendency of infections or any case of leukoencephalopathy. Summary and Conclusion: The results suggest that early use of Rituximab is associated with decrease number of plasma exchanges, increased duration of remission and decreased risk of relapse with excellent safety profile as suggested by earlier studies. We also noticed maximum benefit is seen if Rituximab given at the earliest. We need further randomized controlled trials testing efficacy of upfront Rituximab. Based on these observations, our group is planned for prospective study for the early use of rituximab.

Key words: Relapse, rituximab, thrombotic thrombocytopenic purpura

A-010: International normalization ratio: Comparison between traditional laboratory and point of care testing

Abdulrahman Alsweed, Abdulelah Alsughayyir, Faisal Aseraye 1 , Abdulkareem Al-Momen 1

College of Medicine, Al Imam Mohammad IBN Saud Islamic University, 1 Department of Pathology and Laboratory Medicine, Security Force Hospital, Riyadh, KSA

Background: Warfarin is a vitamin K antagonist anticoagulant which is affected by many dietary and therapeutic agents that commonly increase or decrease vitamin K activity. Therefore, to maintain a safe level of warfarin effect, it has to be monitored by (INR) 2-3 times above control level. INR testing requires drawing a venous blood sample into a citrated tube and transferring it to the coagulation laboratory to get INR done. To do INR by POCT requires only a capillary blood drop to be put on the POCT apparatus at the patient site (or even by the patient him/herself at home). The use of POCT to monitor INR will be more convenient, economic and a major achievement for improved quality of live. The aim of this prospective study is to compare the accuracy of INR testing by POCT at patient site with routine laboratory testing. Patients and Methods: We studied 62 adult patients (30 males and 32 females, aged 40-72 years), who gave consent to participate in this study. Venous blood samples were collected into citrated tubes and transferred to the mail laboratory for routine INR testing. At the same time a blood drop was obtained from each patient through a clean, dry finger prick and put on the CoaguCheck XS apparatus (Roche diagnostics) for immediate on site (POCT) INR testing. Results: The mean INR tested by POCT was 2.42±1.22 seconds, which is comparable to the INR that was tested in the main laboratory, which was 2.22 ± 1.08 s. Conclusion: Results of INR tested on site by POCT were almost identical to those of the routine laboratory. Larger studies that include normal controls and patients on warfarin are needed to confirm our finding before the implementation of INR testing by POCT.

A-011: Application of T-cell receptor-Vß repertoire by flow cytometry in the diagnosis of T-cell neoplasms resulting in a novel approach

Osamah Khojah, Rami Al-Bugami, Faisal Rawas, Nasir Bakshi

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Al Maather, Riyadh 12713, Saudi Arabia

Background: Clonality is a key criterion to establish diagnosis in hematological malignancies. This feature also harbors several implications in treatment choice, prognosis and assessing the efficacy of intervention. In lymphoma, obtaining an evidence of clonality is a major step toward confirming the diagnosis, particularly T-cell and natural killer (NK) lymphomas.However, in many occasions, identification of those clonal malignant cells is not warranted. Therefore, different methods have been used and validated to demonstrate an evidence of clonality. These techniques differ in their principles but they share the same goal which evaluates the sample for any clonal evidences. One of these widely accepted method is the flow cytometry. Previously, clonality assessment for the diagnosis of suspected T-cell neoplasms has largely been based on analysis of rearrangement of the T-cell receptor (TCR) genes.In contrast to B-cells and other myeloid neoplasms, it has been much more difficult to determine T-cell clonality in clinical samples using immunophenotyping until relatively recently, when antibody panels against the T-cell receptor-variable beta (TCR-Vβ) became commercially available. These reagents previously have been demonstrated to provide evidence of clonality in established T-cell malignant neoplasms. In the present study, we evaluate using this newly developed flow cytometric panel to establish clonal T-cell and compare this result to conventional T-cell receptor (TCR) rearrangement by molecular technique. Methods: Appling a relatively new commercially available TCR-Vβ antibody reagents in 32 fresh clinical samples submitted for evaluation of potential involvement by T-cell malignant neoplasms by flow cytometry. Phenotyping strategy for the assessment of TCR-Vβ expression was performed utilizing a commercially-available kit (IOTest Beta Mark TCR-Vβ Repertoire Kit, Beckman Coulter) designed to quantitate 24 different TCR-Vβ specificities, which cover the main family of variable region of beta sub-unit of TCR [Figure 1]. The flow cytometric analysis of the TCR-Vβ repertoire with fluorescently-labeled antibody reagents to specific TCR β-chain variable regions was performed prospectively in 32 clinical cases (between 2008-211) in our institutions' flow cytometry laboratory by using an 8-color Flow instrument (BD Canto II). In addition, twenty cases out of the 32 available samples evaluated by flow cytometry analysis were also investigated for TCR clonality by the conventional molecular method. In the molecular method, monoclonality was identified by examining TCR-gamma region. Finally, the concordance between the results of both methods was investigated in this study. Results: Thirty-two cases were included in this study with median age 37.5 and male to female ratio being 1.3:1. The final diagnosis for these 32 case as followed: 12 cases diagnosed with T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL), 7 patients had peripheral T-cell lymphoma (PTCL) including one case compositing lymphoma (Hodgkin lymphoma/PTCL) and another likely to be PTCL, 5 cases with cutaneous T-cell lymphoma (CTCL), 1 case with anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase negative (ALK-) and also 1 case with T-cell prolymphocytic leukemia (T-PLL). In 6 cases TCR-Vβ was analyzed because of high suspicion but were later diagnosed as non-T-cell lesions. For those six cases there was no evidence of clonality (three cases by both techniques) and flow cytometry was done in the other three cases which showed a polyclonal result. The results of the 32 cases analyzed by flow cytometry TCR-VB repertoire revealed 81%, 100%, 100% and 55% for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), respectively. Similar figures have been obtained by applying molecular testing on 20 samples accounting for 82% sensitivity, 100% specificity, 100% PPV and 50% NPV. The overall concordance between both methods for assessing the TCR clonality is reasonably excellent with 85% (17 cases have the similar results out of 20 cases investigated by both techniques). Discussion: From this current study we evaluated using the flow cytometry as a diagnostic tool for T-cell malignancies by providing an evidence of TCR clonality. The results were encouraging to use this method as a screening tool since it is readily preformed and the results can be obtained within few hours. Molecular method usually takes days/weeks for finalizing the report and it needs more sophisticated laboratory to run such testing. In addition, this study illuminates the administration of TCR-VB by flow cytometry as an upfront method for establishing the clonality by showing that both specificity and PPV equaling to 100%. These high yielded results were compatible with other rare studies investigated TCR-VB repatriate in clinical use. From all the findings and results obtained from our retrospective analysis of these small cohort cases with admitting all the limitations in this study, we strongly recommend a new algorithm for diagnosis T-cell malignancies incorporating utilizing flow cytometry TCR-VB as a powerful and first tool for establishing TCR clonality. Conclusion: This study highlights a novel algorithmic approach to T-cell lymphoproliferative neoplasms, which can be particularly useful in low-cellularity specimens, such as FNA and body fluids. By using this approach only cases with an abnormal T-cell phenotype having equivocal/non-clonal results by TCR-Vβ flow should be tested by molecular TCR. These can potentially be used as a highly sensitive tool for treatment response and early relapse in T-cell neoplasms.



A-012: Comparative analysis of gene expression between plamablastic lymphoma and diffuse large B-cell lymphoma: A single institute experience from Saudi Arabia

Ghaleb Elyamany, Ali-Alzahrani 1 , Shuaa Asiri, Mohammed Awad

Departments of Pathology and Laboratory Medicine and 1 Oncology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia

Background: Plasmablastic lymphoma (PBL) is an aggressive subtype of diffuse large B-cell lymphoma, which shares many morphologic and immunophenotypic features with multiple myeloma (MM). Pathogenesis of PBL is poorly understood in terms of molecular events and signaling pathways; thus limiting the utility of new-targeted therapies. Gene expression profiling (GEP) offers a unique opportunity to comprehensively analyze the phenotype of cell populations and provided insights and better understanding of the pathphysiology, molecular characteristics, and biology of PBL which could help in the development of novel agents or new treatment regimens for PBL. Proteasome inhibitor (bortezomib) which used to blocks NF-κB pathway in MM, thereby sensitizing myeloma cells to cytotoxic chemotherapy, however, clinical efficacy of bortezomib in PBL remains unknown. In this study, we assessed the GEP pattern of most important pathways related to lymphoma ontogeny in a series of PBL compared with similar gene set in reactive lymphoid tissue (tonsils) and aggressive (relapsed) diffuse large B-cell lymphoma. Methods: GEP (154 gene-set) was assessed by Nano string technology, in a cohort (n = 8) of PBL patients; utilizing mRNA from formalin fixed paraffin embedded diagnostic biopsy tissue. This data set was compared with similar gene set in reactive lymphoid tissue (tonsils; n = 30) and aggressive (relapsed) Diffuse Large B-cell Lymphoma patients (n = 60). Diagnosis of PBL was based on morphology and immunoperoxdase staining criteria as established by World Health Organization (WHO) 2008 classification system. We used SPSS softwarev20.0 (IBM Armonk, NY, USA) for statistical evaluation. We obtained institutional ethics board approval for this study, in accordance with the Helsinki Declaration. Results: Summarizes the clinical features and immunohistochemical characteristics of the PBL cases. Table 2 summarize the comparative analysis of gene expression with significant variation in expression either up-regulated or down regulated (minimum 1.5 fold change with P < 0.05) between PBL, DLBCL and reactive tonsil (controls). MYC, CCND2, BIRC5 (survivin), IRF4 and PRDM1 gene pathways are up-regulated in PBL group compared to DLBCL and reactive tonsil whereas GCB signature, BCR genes (namely BCL10/MALT1/CARD11), TLR genes, MYD88 pathway and NF-kB pathway were downregulated. As expected PRDM1/BLIMP-1 was highly expressed (>4.0 fold increase); compared to aggressive DLBCL and reactive tissue, Marked suppression of PAX5/BCR/MYD88 pathway as well as germinal center related genes confirmed the GEP signature of PBL in all pts. Also, all NF-κB-related genes were down regulated in PBL pts.; while downstream genes related to proliferation (c-myc, Cyclin Ds) were up regulated (>1.5 fold change; P < 0.05). This data, signify the differential expression in genetic pathways in PBL from DLBCL and control group. Conclusion: We provided a correlation between GEP related data and morphology/immunophenotype in a small cohort of PBL pts compared with DLBCL and reactive tonsils. Genes related to NF-κB pathway were significantly suppressed in PBL; thus providing initial evidence of altered pathways for high proliferation among PBL pts. This study provides informative data to determine the clinical efficacy and therapeutic importance of Proteasome inhibitors among PBL patients.



A-013: Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients: A systematic review and meta-analysis

R. Dada 1,2 , Rawan Al Saadi 1 , Fawwaz Yassin 1 , Mohamed Bayoumy 1

1 King Faisal Specialist Hospital and Research Center, Jeddah, 2 College of Medicine, Al-Faisal University, Riyadh, Kingdom of Saudi Arabia

Objectives: The outcome of Hodgkin lymphoma (HL) has improved over the past 20 years. However, the probability of relapse after response to initial treatment is currently approximately 10-15% for localized HL (i.e., stage I and II) and 20-40% for advanced stages (i.e., IIIB and IV), dependent on prognostic factors. [1] In young patients eligible for dose intensive chemotherapy, salvage chemotherapy with autologous stem cell transplantation (ASCT) is a frequently used therapy option and can be considered as standard. [2],[3] Patients who relapse following ASCT and those not eligible for myeloablative therapy are being treated with conventional chemotherapy or new novel agents such brentuximab vedotin (BV). Since approval of BV several study groups published the results of their experience in treating refractory/relapsed HL patients with BV. Patients and Methods: The purpose of this study was to evaluate the impact of BV on outcome of patients with refractory and relapsed HL. In this systematic review we analyzed the published data on refractory/relapsed Hodgkin lymphoma patients who received BV as single agent. A systematic literature search was performed and included studies published from 1 st January 2000-1 st July 2015 in PubMed, electronic databases EMBASE (Dialog), Cochrane Library, DIMDI-Recherché and MEDPILOT. We used the key words brentuximab, brentuximab vedotein, adcetris, CD30 antibody and SGN-35. Recent conference abstracts from the American Society for Clinical Oncology (ASCO) (2012-2015) and American Society of Hematology (ASH) (2012-2014) were also included. Serial reports of 5 patients and more were included. If several publications from same author and group were published, the publications were re-scanned whether the reported patients' cohorts are the same. We included patients treated with BV pre- and post-transplantation as well as those not eligible for transplantation. Publications reporting about experience with BV in several diseases, e.g. T cell lymphoma and HL, underwent special analysis in order to extract only the HL data. Studies using BV in combination with radiation were disqualified for our analysis. Results: 51 out of 5369 screened records met the eligibility criteria. These records included 903 patients. The median age of the cohort was 31 year (range: 26-45). 86% received ≥ 3 previous lines of systemic therapy. 529 (58.7%) and 232 (25.7%) underwent high dose chemotherapy and autologous and/or allogeneic stem transplantation prior of BV respectively. The overall response rate to BV was 62.7% (range: 30-100%). The complete response, partial response, stable disease and progressive disease rates were 31.8%, 35.1%, 19.5% and 11.7% respectively. The one year progression free survival and estimated one year overall survival were 47.6% and 79.5% (Fig. 4) respectively. Additional fixed effect model meta-analysis showed similar results (difference: < 2%) except for progressive disease (difference: 9.3%) and progression at one year (difference: 5.2%) [Table 1]. Conclusion: In this largest published pooled cohort BV produces high responses with encouraging progression free and overall survival in relapsed/refractory HL patients. Our results enhance the role of BV in heavily pretreated HL patients.



A-014: Changing trends of adult lymphoma in the Kingdom of Saudi Arabia: Comparison of data sources

Muhammad Shahzad Rauf, Saad Akhtar, Irfan Maghfoor

King Faisal Specialist Hospital and Research Centre, Oncology Centre, Riyadh, Kingdom of Saudi Arabia

Background: Lymphoma is one of the most common malignancies affecting the young Saudi population. This disease has diversified pathologies and clinical stages that necessitate well optimized clinical management. Regular updates of epidemiological behavior of lymphoma from various parts of the world are available but studies from the Kingdom of Saudi Arabia (KSA) in this field are not consistent. Objectives: The aim of this study was to investigate the current trends in presentation and distribution of lymphoma with special reference to incidence and mortality, gender, age, histopathological subtypes, and clinical stages at King Faisal Specialist Hospital and Research Centre (KFSH&RC). Materials and Methods: Our study included lymphoma data from Saudi Cancer Registry, and relative comparison against KFSH&RC tumor registry data, Gulf country data and International Agency for Research on Cancer data. Results: Common tumors in the West (lung, colon, and prostate) were found to be much less frequent in KSA while leukemia, lymphoma and thyroid cancers were more common. Non-Hodgkin Lymphoma (NHL) ranked 3 rd most common cancer with age-adjusted incidence of 6/100,000. Estimated age adjusted mortality was 4/100,000 in KSA. There was a peak rise in incidence of lymphoma in 1997-2007. Most common NHL was diffuse large B cell lymphoma at KFSH&RC. A total of 434 cases were diagnosed in 5 years with 55% of them at advanced stage and 35% demonstrating bulky disease and high risk. KFSH&RC registered 35% of Hodgkins and 21% of total NHL identified in entire Saudi Cancer Registry, 2009. Conclusions: Results of this study are very unique, and reveal diverse trends. The findings provide valuable insights in the understanding of current epidemiological features of lymphoma in this part of the world.

Key words: Epidemiology, Kingdom of Saudi Arabia, lymphoma, Saudi cancer incidence and mortality

A-015: Comprehensive analysis of conventional and molecular cytogenetic studies for acute lymphoblastic leukemia at King Faisal Specialist Hospital and Research Center

M. Al-Majed, O. Khojah, S. Barri, A. Al-Rajeh, S. Khalil

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

Background and Purpose: Acute lymphoblastic leukemia (ALL) is aheterogeneous hematological neoplasm arising from Band T lymphocyte precursors with diverse genetic alterations. Identifying genetic abnormalities is essential for classification, risk stratification, minimal residual disease monitoring and targeted therapy administration. This extensive study provides details of ALL genetic aberrations in our community and compares these findings with international reference data. Methodology: Analysis for bone marrow aspiration of 380 newly diagnosed ALL patients at King Faisal Specialist Hospital and Research Center (KFSH&RC) between 2012-2014 was carried out through karyotyping and a specific fluorescence in situ hybridization (FISH) panel. Depending on the type and age of newly diagnosed ALL patient, the specific FISH ALL panel was selected out of three ALL panels including; pediatric or adult panels for B-cell ALL or T-cell ALL panel. In addition, flow cytometry analysis for DNA index in new pediatric cases were reviewed and compared with classical and molecular cytogenetic studies. Finally, the collected results were also paralleled to the reference data acquiring from the current World Health Organization (WHO) classification for hematological and lymphoid neoplasms. Results: The median diagnosis age was 7 years with a male to female ratio 1.4:1.Cytogenetic and FISH abnormalities were evident in 301 samples (79%) with Pediatric ALL cases representing269 (71%) of all cases, of whichB-ALL being the vast majority (91%). The adult-group consists of 111 patients (29%) of ALL cases with B and T-ALL representing 77% and 23%, respectively. In the B-ALL group, hyperdiploidy, ETV6/RUNX1 translocation, complex karyotype, Philadelphia-positive ALL, hypodiploidy and MLL rearrangement groups were detected by classical cytogenetic, FISH or both in 39% (48% in pediatric-ALL, 13% in adult-ALL), 12% (15%, 0%), 7% (6%, 10%), 6% (2%, 18%), 3% (3%, 4%) and 4% (4.4%, 1.2%), respectively [Table 3]. Deletion of chromosome 9 short arm was occurred in 41% of all T-ALL cases. In Pediatric B-ALL cases, the DNA index analysis revealed 85 hyperdiploidy cases, 4 cases hypodiploidy and 107 normal DNA index cases by flow cytometry analysis. The concordance between FISH and flow cytometry results was reasonably acceptable with 88% of tested samples being matched. However, the overall concordance between the three techniques was only 62%. Conclusion: These enormous data supported the value of applying different diagnostic methods for ALL. Our ALL population might have different prognostic outcome evident by higher hyperdiploidy and lower ETV6/RUNX1 translocation frequencies. Further regional collaborative study between multicenterand correlation with the clinical outcomes are demanded to strengthen theseresults.



A-016: Genetic abnormalities among newly diagnosed plasma cell myeloma patients at King Fahad Medical City, Riyadh

R. Altahan, O. Khojah, R. Alamri, M. Alsharif, L. Alsuhaibani, K. Alsaidi, S. Tashkandi

Department of Pathology and Laboratory Medicine, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

Background and Purpose: Plasma cell myeloma (PCM), commonly referred to as multiple myeloma, is a clonal hematological malignancy arising from plasma cells with a frequent heterogeneity in clinical presentation and genetic abnormalities. In relatively recent epidemiological study, racial differences have been implicated in different genetic changes which harbor different prognosis and outcome. Chromosomes aberrations may be detected in up to 50% of patients with multiple myeloma when classical methods are used. The type of genetic aberration plays an important prognostic factor in multiple myeloma. Depending on the type of chromosomes aberration the median survival rate may be predicted. Thus, evaluating the new cases of PCM for genetic alteration is essential for establishing prognosis and monitoring the disease progression in KFMC population. Evolving of PCM requires a major genetic insult, however, conventional karyotype analysis may detect around 25% of PCM having genetic abnormality. Florescence in situ hybridization (FISH) method can raise the detection power of the genetic abnormality in PCM up to 50%. A far better positive detection of genetic abnormalities can be obtained by using either interphase FISH in purified plasma cells or light chain-restricted plasma cell cytoplasmic immunoglobulin enhanced FISH. This cohort investigates the detection of molecular genetic aberrations among newly diagnosed PCM in our institute with comparison to international published data. Methodology: This is four years' retrospective analysis for newly diagnosed PCM cases in King Fahad Medical City (KFMC), Riyadh, between 2012 and 2015. Forty-eight new cases were diagnosed at KFMC in the study period. However, only 32 new cases were investigated completely for having genetic abnormality through PCM-panel covering five hot spots in chromosome (Ch) 4, Ch11, Ch13, Ch14 and Ch17. Conventional FISH technique was used with five validated and widely applied for PCM genetic abnormalities. These five probe were IGH/CCND1 t(11;14), IGH/FGFR3 t(4;14), IGH break apart probe, TP53 gene deletion (17p13.1) and D13S319 (13q14.3). In addition, a review of the available karyotype results and a comparison with the FISH result were conducted in those cases. The genetic abnormalities in our cases were compared with recently published data from Mayo Clinic including 484 PCM newly diagnosed patients. Results: The median diagnosis age was 60.5 years (37-90 years) and 4 (13%) patients being under age of 40 years in the 32 newly diagnosed patients with PCM. Nineteen and 13 patients were male and female, respectively, with a M:F ratio equaling to 1.5:1. Only 17 (53%) out of 32 cases showed a genetic alteration by classical FISH technique. The total number of genetic abnormalities in these 17 cases is 31 genetic abnormalities which means almost 2 genetic abnormalities were detected per positive FISH patients (ranging from 1 to 4 abnormalities). Out of the 17 positive cases, ten (31%), 9 (28%) and 5 (16%) cases revealed chromosomal deletion, hyperdiploidy (trisomy) and immunoglobulin heavy chain (IGH) rearrangements, respectively. All 9 trisomy cases contained at least trisomy 11 with five cases showing only trisomy 11. Deletion of Ch13 was the most prevalent abnormality which detected in 7 different patients. Classical cytogenetic analysis showed ten cases underwent for karyotyping with a failure rate reaching to 40%. The other six cases showed a normal karyotype which was matched with FISH results I these six cases. The current benchmark study for genetic abnormality in PCM using interphase FISH in purified plasma cells resulted in better yield with 97% positive cases comparing with our study (only 53% positive FISH result) [Table 1]. Conclusion: The genetic abnormality of PCM in our community is substantially unclear, the sample size (32 patients) is considered small to draw prognosis conclusions in comparison to published studies. However, the findings of current study suggest a different landscape of genetic aberrations in Saudis compared to international figures. Also, it favors the notion that classical karyotype should not be included in the routine investigations for PCM. Finally, this study strongly recommends introducing purified/enrichment plasma cell techniques to our lab resulting in enhanced sensitivity and quality of genetic abnormality detection. Moreover,expansion of the FISH probe panel may be an option to re-evaluate the currently applied panel.



A-017: Increased chemotherapy intensity will improve relapse rate but not over-all survival in acute myeloid leukemia patient: A single center experience

Fouzia Al Sobhi, Muhammad Matloob Alam, Mohamed Bayoumy, Ibraheem Abosoudah

Department of Oncology, Section of Pediatric Hematology/Oncology and Blood and Marrow Transplant, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia

Background: Acute myeloid leukemia (AML) represents 15%-20% of all leukemia in children less than 14 years. Over the last few years' treatment modification, intensification, introduction of new chemotherapeutic agents, targeted therapy and concomitant haematopoietic stem cell transplantation (HSCT) in high risk patients has improved overall survival in children with AML up to 50-60%. Methodology: The aim of this single center retrospective study is to describe the clinic-pathological features and outcome of chemotherapy and HSCT in patients admitted with diagnosis of AML between 2005 and 2014 at King Faisal Specialist Hospital and Research Centre (KFSH&RC)-Jeddah, Saudi Arabia. Results: A total of 32 acute myeloid leukemia patients was admitted and treated at our institute during this study periods. Out of them male were 18 (56.3%). Mean age of study population was 6.5 ± 5 years. Fever was the most common presenting complaints 32 (100%) followed by lymphadenopathy 31 (97%), pallor 30 (94%), hepato-splenomegally 29 (91%) and bleeding 19 (60%). Four patients have Down syndrome (12.5%) and CNS involvement were documented in 3 (9.4%). Regarding etiology majority of the patients have De Novo 30 (93.7%) and remaining 2 (96.3%) cases have MDS. Case distribution according to FAB classification was as follow M1 (n = 1; 3.1%), M2 (n = 7; 21.9%), M3 (n = 4; 12.5%), M4 Eo (n = 1; 3.1%), M5 (n = 8; 25%), M6 (n = 4; 12.5%), M7 (n = 4; 12.5%), and no information (n = 3; 9.4%). Cytogenetic were normal in most cases 18 (56.3%) and abnormal cytogenetic was recorded in remaining 14 (23.8%) cases. Out of, complex cytogenetic (n = 2; 6.3%), FLT3/ITD (n = 2; 6.3%), Monosomy 7 (n = 3; 9.4%), t(15;17) in (n = 4; 12.5%) and t(8;21) in (n = 3; 9.4%). Risk group classification was as followed; High risk (n = 10; 31.3%), Intermediate (n = 10; 31.3%) and low risk (n = 11; 34.4%) and not done in (n = 1; 3.1%). Case distribution according to the chemotherapy protocol used for treatment were POG 8498 protocol (n = 15; 46.9%) and AAML 0531 protocol (n = 13, 40.6%). Remaining 4 (n = 4, 12.5%) patients with diagnosis of APL were treated with C9710 protocol. Complete remission after 2 cycle of induction chemotherapy was achieved in 23 (71.3%) cases, 6 (18.8%) cases experienced induction failure and another 3 (9.4%) patients expired during induction chemotherapy and/or lost to follow up. Fungal infection was observed in two cases (n = 2; 6.3%), one had is documented Candida infection and this patients did not recover and expired. Sixteen patients received allogeneic HSCT after chemotherapy (8 belongs to high risk, 6 intermediate risk and 2 low risk group), out of them 12 were in complete remission and 4 patients were not in remission at the time of transplantation. Out of 8 patients who belongs to high risk group 3 were relapsed and 1 expired and out of 6 patients who belongs to intermediate risk group, 3 were relapsed and 1 expired after HSCT. Overall relapse rate in group of patients treated with AAML 0531 and POG 8497 were (n = 6/28; 21.4%) with mean duration of relapse 26±27 months. Relapse rate in patients treated with AAML 0531 protocol were much lower than those who treated with POG 8497 protocol (15% vs 27%). Overall mortality rate were (n = 8/32; 25%) mean timing of expiry from diagnosis is 37±32 months with mean duration of follow up is 48 ±6.5 months. Mortality rate in both group of patients who were treated with AAML 0531 protocol or POG 8497 protocol were comparable (31% vs. 27%). Conclusion: We observed better event free survival in our patient treated with AAML 0531 protocol, however overall survival were comparable with patient those treated with POG 8497 protocol. Further large scale, multicenter and long-term follow up study will be required to validate these findings.

A-018: CD20 expression is associated with higher risk of early relapse at 1 year following chemotherapy treatment for adolescent and adult acute lymphoblastic leukemia patients

Feras Alfraih, Dennis (Dong Hwan) Kim 1 ,

Abdul Mannan, Ghuzayel Aldawsari, Fahad Alsharif, Hazzaa Alzahrani, Said Yousuf Mohamed, Walid Rasheed, Amr Hanbali, Syed Osman Ahmed, Marwan Shaheen, Fahad Almohareb, Mahmoud Aljurf, Naeem Chaudhri

Department of Oncology, Hematology and Allogeneic Bone Marrow Transplant Program, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia, 1 Department of Medical Oncology and Hematology, Allogeneic Blood and Marrow Transplant Program, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada

Introduction: It is extremely significant to predict treatment outcomes using a biomarker. The prognostic significance of CD20 expression is controversial. In this study, we attempted to evaluate the impact of CD 20 expression on treatment outcomes in large cohort of adolescents and adults patients with acute lymphoblastic leukemia (ALL) treated in one single center. Methods: A total of 172 adolescent and adult patients with newly diagnosed B precursor ALL receiving CALGB based chemotherapy protocol between year 2001 and July 2014 at our Centre were evaluated for the expression of CD20 and it is impact on treatment outcomes. Anti-CD20 monoclonal antibody use were not part of the chemotherapy protocol at our Centre. Patients underwent hematopoietic stem cell transplantation were excluded from the analysis, a total of 83 patients were finally included in the analysis. CD20 expression at diagnosis of 20% in blast population was used as cutoff to stratify patients as CD20 positive (CD20+) versus CD20 negative (CD20-) group. Results: Median age for all patients is 21 years (range, 14-62), 41% (n = 34) were females. Median WBC at diagnosis was 8 (range, 0.4-244), 28% (n = 23) had WBC > 30. Philadelphia chromosome was negative for 75 patients (86%) while positive for 12 patients (14%). Day 28 blasts < 5% was for 78 patients (90%), 5% with blasts > 5 (n = 5) and missing for 4 patients (5%). A median follow-up of 3.7 years for survivors (range, 1-11) showed 29 patients (35%) had CD20+ versus 54 patients (65%) was CD20-. The cumulative incidence of relapse at 1 year for CD20+ was 42% versus 15% (P = 0.05) for + CD20 [Figure 1] while 5 years relapse rate was 55% versus 58%, respectively, suggesting higher incidence of 1 year relapse in CD20+ group. The overall survival and disease free survival was 41%, and 41% in CD20+ group versus 46%, and 37% (P = 0.70) in CD20-group, respectively. In Univariate analysis for One-year relapse, CD20 expression was significant factor (P = 0.02, HR = 2.97). Multivariate analysis confirmed CD20 as an independent adverse risk factor for relapse at 1 year (P = 0.02, HR 2.97). For 5-years relapse, male gender (P = 0.03, HR 2.1) and age > 30 years (P = 0.05, HR2.38) were found to be independent factors but not CD20 expression. For NRM, day 28 bone marrow with blast > 5% (P < 0.001, HR 5.29), WBC > 30 (P = 0.01, HR 8.3) and high LDH (P = 0.002, HR 1) were the only independent prognostic factors. Conclusion: The present study showed that the overall incidence of CD20 expression in B-ALL is 35%. Also, it suggested that in non-HSCT patients, CD20 expression at a diagnosis is associated with higher risk of early relapse at one year, which was confirmed by multivariate analysis. Further study is strongly warranted to confirm the prognostic role of CD20 and to evaluate the importance of anti-CD20 monoclonal antibody in a prospectively designed study for.



Key words: Acute lymphoblastic leukemia, CD20, hematopoietic cell transplant

A-019: High-dose chemotherapy and auto-stem cell transplant for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy

Muhammad Shahzad Rauf, Irfan Maghfoor, Tusneem Ahmed M. Elhassan, Saad Akhtar

King Faisal Specialist Hospital and Research Centre, Oncology Centre, Riyadh, Kingdom of Saudi Arabia

Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo highdose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996 to 2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16%, partial response (PR) 71% and stable disease 13%. After HDC auto- SCT, CR:PR: progressive disease was observed in 18 (58%): four (12%): nine (29%) patients, respectively. Five-year overall survival (OS) for whole group is 57% (Rel:Ref vs. Ref:Ref, 73% vs. 48%, P = 0.48). Progression-free survival (PFS) for whole group is 52% (Rel:Ref vs. Ref:Ref, 73% vs. 40% respectively, P = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse- refractory and refractory-refractory group of patients.

Key words: Autologous stem cell transplantation, refractory Hodgkin's lymphoma, salvage chemotherapy, second-line salvage chemotherapy

A-020: Cytogenetics and molecular markers in acute myeloid leukemia

A. Alrajeh, H. Abalkhail, O. Khojah, M. Almajed, S. Ramadan, S. Khalil

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital, Riyadh, Kingdom of Saudi Arabia

Background and Purpose: Acute myeloid leukemia (AML) is a phenotypically and genetically heterogeneous disease. This heterogeneity is attributed to alterations in genetic bases. AML classification based on these abnormalities is essential for accurate diagnosis, risk stratification, prognostic value, monitoring of minimal residual disease and developing targeted therapies. This study evaluates frequency of each karyotype and molecular abnormality at our institution with comparison to other international studies. Methodology: We reviewed 100 bone marrow samples which represent all AML diagnosed cases at KFSH&RC from 2012 to 2014 by conventional karyotyping, specific AML-FISH panel and variety of AML-specific mutations using Sanger sequencing. Results: Out of 100 AML patients investigated with median age of 29 years, 98 were successfully karyotyped, 64% of cases had an abnormality. In addition, all 100 AML-FISH panel and molecular studies were informative with an abnormality reaching 50% and 45%, respectively. Conventional and molecular cytogenetic studies revealed trisomy 8 (15%), t(8; 21) in 12%, trisomy 21(8%), inv(16) in 7%, t(15;17) in 6%, 11q rearrangements (6%),and inv (3) in 2%. The mutational analysis showed NPM1 (12%), FLT-3-ITD (9%), IDH2 (7%), IDH1 (6%), WT1 (5%), DNMT3A (4%), CEBPA (4%) and c-KIT (3%). Two-thirds of FLT3-ITD and NPM1 cases with normal karyotype while all 3 cases of c-KIT mutation with abnormal karyotype. Conclusion: The incidence of abnormal karyotype is higher in our population while mutational analysis attained lower frequency compared to different international centers. This is the first cytogenetic data from Saudi Arabia for AML including genetic mutations. Therefore, a multicenter collaboration and comprehensive study is recommended to confirm these findings.

A-021: Molecular cytogenetic analysis of 103 newly diagnosed plasma cell myeloma patients resulting in a novel biphasic approach

O. Khojah, A. Al-Rajeh, M. Al-Majed, S. Ramadan, N. Al-Mozain, F. Al-Sharif, S. Khalil

Department of Pathology and Laboratory Medicine and Adult Hematology, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia

Background and Purpose: Plasma cell myeloma (PCM) is a hematological neoplasm arising from clonal plasma cells due to acquired genetic alterations especially in advanced age. It is relatively common accounting for an approximately 1% of all malignancies and 15% of all hematological neoplasms with a slightly male predominance. The initial prognostication and monitoring of the disease progression can be obtained by identification of plasma cell genetic abnormalities. In previous studies, analysis of newly diagnosed patients with PCM revealed a genetic abnormality rate in about 20-30% and 50-60% by convictional karyotyping and fluorescence in situ hybridization (FISH), respectively. More recent studies showed a substantial improvement in detection power of genetic alterations reaching 97% if a modernistic molecular cytogenetic technique used. Furthermore, neoteric reports displayed a racial difference in genetic alteration among PCM patients. This retrospective study evaluated the molecular cytogenetic aberrations at our institution in a cohort of newly diagnosed patients with comparison to internationally published data. Methodology: All adult bone marrow reports done between 2012 and 2015 were reviewed to identified the newly diagnosed PCM patients. The total number of newly diagnosed patients is 103 patients in the study period. However, 90 patients had a completed molecular cytogenetic study in our institute. The molecular cytogenetic study used FISH interphase technique examining at least 200 cells from bone marrow aspiration sample by two different skillful clinical cytogeneticists. The current validated PCM-FISH panel included five different probes; trisomy 12q15, deletion 13q14/13q34, deletion 17p13.1, translocation (11;14) and translocation (4;14). Results: Ninety newly diagnosed PCM patients with a median age of 55.5 years (range: 25-87 years) and 12% of all patients <40 years. Fifty-three patients were male and 37 were female with male to female ratio of 1.4. Moreover, 72 (80%) in-house and 18 (20%) referral cases were investigated. The FISH-panel detected genetic abnormalities in 66 (73%) of analyzed bone marrow samples with an average of 2.2 abnormalities per positive sample. The hyperdiploidy/ trisomy, hypodiploidy/monosomy and immunoglobulin heavy chain (IGH) rearrangement were detected in 40 (44%), 30 (33%) and 19 (21%) cases, respectively, with 15 (17%) cases showing mixing abnormalities. Trisomy of chromosome (Ch) 11 was positive in 39 (43%) cases and monosomy of Ch 13 was detected in 30 (33%) cases. Moreover, deletion of Ch 17 was reported in 8 (9%) of all investigated samples [Table 2]. Classical karyotype study was done in only 13 samples that revealed 62%, 23% and 15% as negative and positive results and failure rate. However, all the negative result cases by karyotyping showed at least one abnormality by FISH method. Other diagnostic laboratory investigations were also incorporated in this study. Conclusion: This is the first reported molecular genetic study using FISH method from Saudi Arabia for newly diagnosed PCM patients showing an early age of onset and a significant difference of genetic abnormality comparing with international reports, namely IGH rearrangements. These observations support a recently published data demonstrated racial differences in PCM characteristics. Furthermore, this study was valuable in implementing a new biphasic PCM- panel approach including two phases; screening and comprehensive.



A-022: FOXP3+ can predict overall survival and risk of transformation in uniformly treated patients with mycosis fungoides

Rami Al-Bugami, A. Al-Mutawa, M. Al-Ghamdi, O. Khojah, Nasir Bakshi

Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Background: Mycosis fungoides (MF) is an extra-nodal T-cell non-Hodgkin lymphoma (NHL) characterized by involvement of skin. It accounts for around 4% of all cases of NHL and half cases of cutaneous T-cell lymphoma (CTCL) with a majority of cases being diagnosed around age of 60 years. MF is more prevalent in black individuals and predominantly affects male with ratio 2:1 comparing with female. It is a heterogeneous lymphoid neoplasm with a variable clinical course. In early stages, MF often runs an indolent course. A small, but significant, part of these patients develops an aggressive course frequently associated with inferior survival. Several hypothesizes have been investigated for pathogenesis of MF, including immunological cytokines, adhesion molecules, role of some viral infections and genetic alterations. However, the initiation insult for MF pathogenesis is still largely unclear. Furthermore, no consistent biological markers are known to be predictive of survival or risk of transformation (RT). Forkhead box P3 (FOXP3) belongs to a novel forkhead transcription factor essential for the development and regulation of regulatory T-cell (Treg) which has been implicated in the pathogenesis of MF. Recent studies have shown conflicting results when expression of Foxp3 was analyzed as a prognostic factor in MF. We hypothesized that FOXP3 could be an important marker in predicting for overall survival (OS), progression-free survival (PFS) and RT in MF patients managed by uniform treatment regimens. Methods: Forty-two patients with newly diagnosed MF were retrieved form the record files between 2007-2009. All patients were managed and treated at our institute (King Faisal Specialist Hospital and Research Centre in Riyadh). However, the completed follow-up and pathological material (paraffin blocks) were available for 35 patients out of the original number (42 patients). In all 35 cases, the diagnostic biopsies were reviewed concurrently by an expert dermatopathologist and hematopathologist and diagnosis was fully confirmed. The diagnostic biopsies were immunostained with CD3, CD4, CD7, CD8, CD30 and CD56 specific antibodies. Clonality for TCR gamma was performed in most of the cases in the study 30 cases (86%). FOXP3 antibody (clone 221D/D3) recognizes the FOXP3 in the nucleus with high specificity. Hence, this antibody does not cross react with other forkhead transcription proteins. Therefore, it was utilized for studying the FOXP3 expression by the tumor cells and per-malignant lymphocytes. In addition, twenty cases of reactive non-neoplastic dermal lesions including lichen planus, lupus and dermatitis were also immunostained for FOXP3 for comparison. Only high intensity nuclear staining was considered as positive expression for FOXP3. Using this approach, a semi-quantitative estimation strategy was followed as: no expression (0), expression < 10% (1+), 10-50% (2+) and > 50% (3+). Both the cell content and immuno-architectural pattern were determined. Furthermore, staging of MF was defined according to the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC), 2005. Age, sex, clinical presentation, stage of disease compared to FOXP3 expression by chi- square and Fishers's exact test. The Kaplan-Meyer method and log rank test were used to evaluate survival data. Results: Thirty-four of 35 (97%) patients were alive at 8 years after initial conformation of the diagnosis. Nineteen out of 35 (54%) patients were females and the other 16 (46%) were males. The median age at diagnosis was 44 years (range 7-80 years). The tumor staging result was as follows: stage 1A (57%), 1B (25%), 2A (6%), 2B (6%), 3 (6%). FOXP3 expression showed predominantly intra-epidermal or basal localization of tumor cells. In most of the cases the epidermotropism and the nuclear atypia was helpful in easily discerning tumor cells from reactive non-neoplastic Tregs. Reactive dermal lesions served as an excellent control in that the distribution of Tregs in these lesions was predominantly dermal and rarely basal. Overall 28 of 35 (80%) cases and the remaining 7 (20%) cases were positive and negative for FOXP3, respectively. There was no significant correlation between pattern of involvement and marker expression. Seventeen patients out of 28 cases whom were positive for FOXP3 (61%) had disease whereas the rest 11 (39%) patients were free of disease at the last follow-up (FU period of the study 12-96 months) (P = 0.05, Fisher's exact test). Thirteen out of 28 positive cases (46%) patients were found to have relapse of disease after initial response compared to only 2 out of 7 (28.5%) patients, who relapsed but lacked FOXP3 expression (P = 0.242, Fisher's exact test). Comparing disease progression and aggressiveness as evidenced by lymph node metastasis or progression to Sezary syndrome: only FOXP3 positive cases (4 versus 0) had evidence of disease progression (3 lymph node metastasis alone and one Sezary syndrome) which indicating increased RT. One patient who died of widespread disease showed > 30% Foxp3 expression in the neoplastic lymphoid cells. Conclusions: Specific biological markers for outcome and prognosis in mycosis fungoides remain elusive. A regulatory T-cell phenotype defines a subset of MF patients who might carry a poorer prognosis comparing with FOXP negative MF and might require more aggressive protocol and/or targeted therapy. Further data on the role of FOXP3 expression in cutaneous T-cell lymphomas and its clinical significance is needed.

A-023: Concordance between conventional and molecular cytogenetic techniques in identification of genetic abnormalities among newly diagnosed multiple myeloma patients

O. Khojah, M. Al-Majed, A. Al-Khayat, A. Al-Harbi, A. Al-Maeen, M. Al-Balwi 1 , N. Al-Atawi 1 , A. Al-Suhaibani

Department of Pathology and Laboratory Medicine, Hematology Unit, King Abdulaziz Medical City, 1 Department of Pathology and Laboratory Medicine, Cytogenetic and Molecular Unit, King Abdulaziz Medical City, National Guard, Riyadh, Saudi Arabia

Background and Purpose: Multiple myeloma (MM), also known as plasma cell myeloma, is a clonal hematological malignancy accompanied by abnormal proliferation of plasma cells that is related to an underlying genetic alteration. It is a relatively common neoplasm in elderly with deleterious end organ damage, if left untreated. Identifying of the genetic basis of the disease aids in prognostication as well as disease progression monitoring. Unfortunately, there is no published data about the genetic abnormalities in MM Saudi patients. Previously, genetic abnormalities were detected only in 50-60% of newly diagnosed patients. However, with the advent of plasma cell enrichment techniques, detection rate has been substantially enhanced reaching over 90%. This study reviewed the genetic abnormalities of newly diagnosed patients in our center by two methods and comparing the results with a well-established international data. Methodology: This retrospective study identified 69 newly diagnosed patients with MM in King Abdulaziz Medical City, National Guard Hospital, Riyadh, between 2012 and 2015. However, only 58 patients were included in this study since they had complete cytogenetic investigations. All of these 58 patients underwent MM-panel testing with florescence in situ hybridization (FISH) technique as well as classical cytogenetic analysis by karyotyping. The validated MM-FISH panel included five different probes; trisomy 12q15, 13q14/13q34 deletion, 17p13.1 deletion, translocation (11;14) and immunoglobulin heavy chain (IGH) rearrangement on chromosome (Ch) 14. Results: In this cohort, the median age at diagnosis was 64.5 years, ranging from 39 to 91 years with only two cases were younger than 40 years. Male cases were predominant with the male to female ratio of 3.1:1. Karyotype analyses were done on 54 cases, showing failure or very low yield in 10 cases (18.5%) and evident structural or numerical chromosomal abnormalities in 11 cases (20.4%). In contrast, FISH studies were able to detect 41 positive cases out of 58 cases (70.7%). The overall concordance rate between both methods was only 46.3% [Table 1]. Only a single case showed a genetic abnormality by karyotyping not detected by MM FISH panel. Hyperdiploidy (including trisomies), IGH rearrangements, deletion of Ch 13/13q and Ch 17/17p and hypodiploidy were detected by FISH in 43.1%, 20.7%, 24.1%, 3.5% and 10.3%, respectively. Conclusion: This study shed light on the pattern of genetic alterations among multiple myeloma patients in Saudi Arabia. In such contexts, FISH turns out to be a superior tool for detection of cytogenetic abnormalities compared with conventional karyotyping, yet rarely some cytogenetic abnormalities not included in the MM FISH panel, may be missed. Implementation of plasma cell enrichment technique to increase the detectability of cytogenetic abnormalities by karyotyping is urged. Finally, correlation of these findings with the clinical behavior of each individual patient will refine our understanding of the impacts of a specific or combined genetic abnormality(IES) on our population.



A-024: Efficacy and safety of brentuximab vedotin in combination with bendamustine as 2nd line salvage therapy and potential "bridge" to stem cell transplantation for patients with refractory Hodgkin Lymphoma

Eshrak Shaibani, Panayotis Kaloyannidis, Mohammed Ali, Ahmed Al Shaghier, Khalid Al Anezi, Hani Al Hashmi

Adult Hematology and SCT, King Fahad Specialist Hospital, Dammam, Saudi Arabia

Background: High dose chemotherapy and autologous stem cell transplantation (autoSCT) represents the most reliable curative approach for patients (pts) with refractory or relapsed Hodgkin's lymphoma (HL) after induction therapy. Nevertheless, the outcome of pts failed post 1 st line salvage therapy is extremely poor and only 15-20% can achieve long term survival. For the majority of these pts the 2 nd salvage regimen remains ineffective; therefore there is an unmet need for more effective and less toxic approaches. Brentuximab vedotin and Bendamustine have been tested as single-agents in refractory CD30+ lymphomas, demonstrating significant activity and a favorable safety profile. However, the published data of their combination (B&B) as salvage treatment are to date limited. Materials (or Patients) and Methods: In the present study we evaluated the efficacy and safety of the B&B combination in 6 HL-pts, aged of 26(17-34)ys and disease that had be proven to be refractory after at least 2 prior cycles of ESHAP given as 1 st salvage treatment, while 1 pt had also undergone prior autoSCT. Following a median of 12 (7-31) months since initial diagnosis, the B&B-treatment was administered in an outpatient basis by i.v. infusion of 1.8 mg/kg brentuximab on day-1 and 90 mg/m2 bendamustine on days-1 and 2, in 3-week cycles. At the time of B&B initiation, the disease stage was II, III and IV in 2, 2 and 2 pts respectively, while 2 pts also had B-symptoms. Results: After a median of 2 (2-5) cycles, 4/6 (67%) pts achieved very good remission (>80% metabolic response with PET/CT criteria) while in 2/6 (33%) the disease progressed. No major toxicity (WHO ≥3) was observed during therapy. Finally, all 4 responders underwent stem cell transplantation at a median of 1.5 (1-2.5) months post B&B therapy. One out of four responders (previously treated with autoSCT) underwent alloSCT following RIC, while 2/4 responders mobilized successfully (collected CD34+cells: 7.7 and 4.1 × 106/kg); in one pt the stem cell graft was collected prior to B&B treatment. All transplanted pts are alive and well at a median of 4, 5 (2-5) months post autoSCT. The 2 non- responders pts currently are alive, on palliative treatment for 5 and 10 months. Conclusion: Our data, though restricted to a small number of pts, are in line with the limited published studies and support the evidence that the B&B treatment could be an efficacious, safe and promising approach for maximizing responses prior SCT in patients with refractory HL. The B&B combination merits further investigation in order to clarify its exact role as salvage treatment and a potential "bridge" to successful SCT in refractory lymphomas.

Key words: bendamustin, brentuximab vedotin, Hodgkin lymphoma, salvage therapy

A-025: High-dose melphalan as single-agent regimen for autologous stem cell transplantation in Hodgkin lympoma patients: Comparative study to standard BEAM regimen

Kalogiannidis Paniotis, Kanfer Solaf, Al Azar Khalid, Aljamily Mohammed, Al Anzi Wael, Al Hashmi Hani

Adult Hematology and SCT, King Fahad Specialist Hospital, Dammam, Saudi Arabia

Autologous stem cell transplantation (ASCT) is the treatment of choice for selected patients (pts) with relapsed/refractory Hodgkin lymphoma (HL). Though BEAM is the most widely used regimen, still remains questionable if really represents the optimal preparative approach. High dose melphalan (HDM) as single-agent conditioning regimen has already been used by few centers, demonstrating sufficient efficacy, acceptable toxicity and cost-effectiveness. However, the overall experience is limited and so far there are no data compared to the BEAM regimen. We retrospectively analyzed and compared the results for HDM vs. BEAM regimens in terms of efficacy and toxicity in HL-pts with sensitive disease pre-ASCT [complete (CR) or very good partial remission (VGPR)], autografted in 2 different centers. To estimate the differences between the 2 groups we used the chi-square and T-test while for the survival rates the Kaplan-Maier method. Thirty four pts (17 from each center), selected to be paired regarding age (--vs. --ys p = ns), sex (8 vs. --females and 9 vs. --males p = ns) and disease status before ASCT (6 vs. 6 in CR and 11 vs.8 in VGPR, p = ns) were enrolled in this study. The pts in BEAM-group had been salvaged with 3(2-8) cycles of ESHAP (n = 10), mini-BEAM (n = 2), Gemcitabine-based (n = 2), while the majority of pts in the HDM-group had previously received 4(2-6) cycles of ESHAP (n = 13), DICEP (n = 7), ICE (n = 2), Brentuximab (n = 2), as salvage treatments. All the patients were engrafted and the median day for Neutrophils > 500/mm3 was 11 vs.14 (P = 0.04) and for plts >25000/mm3 13 vs.10 (P = ns) for the HDM and BEAM group respectively. The 4-ys overall and progression free survival were --% and --% in the HDM-group vs. --% and --% in the BEAM-group. No treatment related mortality (TRM) was noticed in the BEAM-group, while in the HDM-group 1/17 died because of TRM (probably corona-virus-related pneumonia). No other organ or tissues toxicities (WHO grade ≥ 3) were observed in both regimens. Interestingly, for the HDM-group the median total hospitalization period (including the regimen administration) was 16 (14-48) days, that favorable compared to the usual required total hospitalization period for the BEAM-regimen (≥18 days). In conclusion, this study, though retrospective and with small series of patients, showed that in patient with sensitive disease before ASCT, the HDM preparative regimen compared to the standard BEAM has equal efficacy, no grade ≥3 regimen-related toxicity (organ/tissue) and acceptable TRM. Moreover, the significant shorter periods in terms of neutrophils-recovery and hospitalization, may contribute to a better cost effectiveness for the HDM-regimen compared to multi agents conditioning regimens.

A-026: Do persistent blasts on a day 14 bone marrow influence survival in patients undergoing allogeneic HSCT in CR1

Muhamad Almahayni, Ali Alahmari, Syed O. Ahmed, Ahmed Alhuraiji, Ahmad Alotaibi, Rehab Albloushi, Osama Ali, A. J. M. Saleh, Naeem Chaudhri

King Faisal Specialist Hospital, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Introduction: The prognostic impact of a bone marrow done 7-10 days after completion of induction chemotherapy for AML is debatable. It is not certain whether in patients undergoing allogeneic transplantation (Allo) in CR1, the presence of disease on day 14 bone marrow renders them at a higher risk of post transplant relapse or inferior survival. Materials (or Patients) and Methods: We identified 35 adolescent and young adult patients on our prospective AML database who had received induction chemotherapy with either ICE (idarubicin, cytarabine, etoposide) or standard 3 + 7 and then had an Allo in CR1. All patients had a day 14 bone marrow. The standard protocol involved giving a second cycle of re-induction with fludarabine/high dose Ara-C or mini-ICE. Patients in CR had either Allo from HLA matched sibling (n = 34) or from matched unrelated donor(n = 1). Results: There were no significant differences between the two groups in terms of age, sex, mean WBC or cytogenetic risk group. Among the 12 patients with day 14 marrow +ve, 11 patients had a 2 nd cycle of induction before day + 21, while one patient had re-induction due to persistent blasts on day 28. Nine pts had 2 courses of induction to achieve CR, while 3 patients had 3 induction courses. All patients with day 14 marrow −ve achieved CR with one induction course. The overall survival for the whole cohort was 68%; patients with day 14 +ve marrow had OS 58% vs. 73% OS for patients with day 14 −ve marrow (P 0.3). The EFS between the 2 groups 65% vs. 58% for day 14 −ve and day 14 +ve respectively (P 0.6). Conclusion: In this cohort of young adult patients who underwent an Allo in CR1, the presence of >5% blasts on a day 14 bone marrow biopsy did not appear to have an impact on OS or EFS, where patients are routinely given a 2 nd cycle of induction for persistent disease. This data will need to be validated in a larger cohort of patients, ideally in a prospective setting.

Key words: acute myeloid leukaemia, allogeneic hematopoietic stem cell transplantation, prognostic factors, response assessment

A-027: Brain infarction and blasts with bilobed nuclei in a patient with monocytic acute myeloid leukemia mimicking acute promyelocytic leukemia

Assem A. Elghazaly, Mamoun H. Ibrahim, Layla A. AlGwaiz 1

Department of Adult Hematology/HSCT, King Fahad Medical City, 1 Department of Pathology and Laboratory Medicine, King Fahad Medical City, Riyadh, Saudi Arabia

We are presenting a case of an adult male patient with monocytic acute myeloid leukemia (AML) who had on presentation brain infarction and bilobed nuclei had been demonstrated in many of the leukemic blasts. There was no laboratory evidence of acute disseminated intravascular coagulopathy, on presentation or later on. Initially the diagnosis of acute promyelocytic leukemia (APL) was considered, so all trans-retinoic acid (ATRA) was added to induction chemo therapy. As the diagnosis of APL was ruled out, based on the flow cytometry, fluorescent in situ hybridization and polymerase chain reaction findings, the ATRA was discontinued and the patient continued on the standard AML chemo therapy induction regimen. Later on chromosomal analysis was also normal. Sever dehydration on presentation, would have contributed to brain infarction. AML particularly monocytic, can mimic APL, especially its microgranular variant. The possible ATRA therapy side effects, can be avoided by early confirmation of the diagnosis.

A-028: Retrospective observational study on multiple myeloma cases admitted to King Fahad Specialist Hospital: Dammam between 1st of June 2006 till the end of December 2013

Omar Zeid Abduljalil, Hani Hassan Al Hashmi

Adult Hematology and SCT, King Fahad Specialist Hospital, Dammam, Saudi Arabia

Introduction: Multiple myeloma (MM) is characterized by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin. It accounts for approximately 1% of all cancers and slightly more than 10% of hematologic malignancies in the United States. There is a scarcity on the information of myeloma in the kingdom of Saudi Arabia, The exact incidence and prevalence of this malignancy is not known in the kingdom of Saudi Arabia. The last report on Multiple Myeloma previously done in the country was at King Faisal Specialist Hospital and research center in Riyadh. However, it was published in 1991 in The Annals of Saudi Medicine, which is more than 2 decades ago. Considering how the therapeutic landscape and overall survival has undergone tremendous improvements since then, a new study was needed in the country to reflect those changes, hence was this observational research from a single center in Dammam, Saudi Arabia. Methods: Retrospective chart review of consecutive patients Diagnosed with Multiple myeloma in the period between first of June 2006 until end of December 2013 at King Fahd Specialist Hospital in Dammam (KFSHD). Purpose: To describe the presenting characteristics of MM patients in our region, treatment patterns prescribed with the outcome of therapy that include progression free survival and overall survival. Results: A total of 63 patients with multiple myeloma were diagnosed and treated during this period. The percentage of patients with ECOG (≥2) is 52.3%. 60% of the patients had stage III international staging system (ISS). Only 17.4% received Triple agents as primary therapy as most of our patients received duplet therapy. 46% received High Dose therapy and autologous stem cell transplantation. The PFS was 41.1% and the OS of 69.1% at 95 months. Conclusion: Our results showed that we had rather younger patient population with a median age of 60 compared to the average western myeloma patient population. Despite the relatively young age, those patients unfortunately had relatively poor performance status and high ISS stage which correlate with worse clinical outcome. However, the response to therapy and the outcome of our patients were superior to the outcome of any cohort of patients with similar disease characteristic. This observation worth further studying which could be due to an unknown disease or treatment related factors that might affect positively the patient's outcome.

A-029: Diffuse large B cell lymphoma with secondary central nervous system involvement is associated with dismal outcome-King Fahad Medical City, Riyadh experience

I. Tailor, T. Hussain, W. Alshakweer 1 , G. Murtaza, I. Motabi, S. Z. A. Zaidi, N. Alshehry, M. Alghamdi, A. Elghazaly, S. Almudaibigh, Y Bayoumi 2

Departments of Adult Haematology/Bone Marrow Transplantation, 1 Pathology and 2 Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia

Background: Secondary central nervous system (CNS) involvement with diffuse large B cell lymphoma (DLBCL) is associated with poor outcomes. We looked at characteristics and outcomes of these patients treated at King Fahad Medical City, Riyadh over 10 year period from 2005 to 2015. Methods: Out of 1235 patients diagnosed with lymphoma at our centre over a ten year period from 2005 to 2015 we identified 8 adult patients over the age of 18 years, who had DLBCL with secondary CNS involvement. It was a retrospective chart review. Results: Out of 8 patients, 3 were males and 5 were females.7 of 8 were over 45 years of age. All patients had stage III disease or beyond with atleast one extranodal involvement. All patients had evidence of parenchymal brain involvement either radiologically or histologically or both.3 of 8 patients presented with concurrent CNS involvement while 5 of 8 had CNS involvement due to progression whilst on treatment or relapse within six months. 2 of 8 patients who did not have CNS involvement at presentation developed CNS disease later despite CNS prophylaxis (one patient received high dose methotrexate, the other received intrathecal chemotherapy).Treatment regimens were variable but included High Dose Methotrexate, High Dose Cytarabine or both, Whole Brain Radiotherapy, anthracycline containing combination chemotherapy including Rituximab, Intrathecal Chemotherapy, Temozolamide. All patients received Rituximab. Only one patient could undergo autologous stem cell transplant but relapsed shortly afterwards. Out of the evaluable 7 patients (one was lost to follow up), 5 patients were uniformly refractory to chemotherapy or radiotherapy or both. Two patients were unfit to receive any treatment and died within a month of diagnosis. Median survival was only four months from the time of CNS involvement (range: 1-7 months). Discussion: To our knowledge this is the first case series of DLBCL with CNS involvement from Middle East. This study shows that CNS involvement is rare but associated with extremely poor outcome as shown in other studies, with a median survival of only 4 months. None of the patients were responsive to therapy. Further studies are needed to define incidence and characteristics and outcomes of these patients from this region. There is certainly need for improvement in how we manage these patients with probable inclusion of novel b cell antagonists in the therapy through well designed clinical trials.

A-030: Outcome of patients with primary central nervous system lymphoma over a 10 year period from 2005 to 2015-King Fahad Medical City, Riyadh experience

I. Tailor, T. Hussain, W. Alshakweer 1 , G. Murtaza, I. Motabi, S. Z. A. Zaidi, N. Alshehry, M. Alghamdi, A. Elghazaly, S. Almudaibigh, Y. Bayoumi 2

Departments of Adult Haematology/Bone Marrow Transplantation, 1 Pathology and 2 Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia

Background: Primary central nervous system lymphoma (PCNL) is very rare and there is little data on the incidence and prevalence, outcomes of these patients from middle eastern region.We tried to look at characteristics and outcomes of these patients treated at King Fahad Medical City, Riyadh over 10 year period from 2005 to 2015. Methods: We did a retrospective study of 1235 patients diagnosed with lymphoma at our centre over a ten year period from 2005-2015 and we identified 10 adult patients over the age of 18 years, who had PCNL. Results: Out of 10 patients, 4 were males and 6 were females. 7 of 10 were over 45 years of age. 8 of 10 patients had ECOG performance status of 3 or more. Histologically, 8 of 10 patients belonged to diffuse large b cell lymphoma, one was primary burkitt's lymphoma of the brain and the other was primary T cell lymphoma, both of which are very rare. Two patients received Whole Brain Radiotherapy only, four patients received High Dose Methotrexate (HD MTX) with High Dose Cytarabine (HD ARA C).Two patients were unstable to receive any treatment and died due to brain biopsy related complications and lymphoma related complications respectively. Four patients received chemoradiation. Rituximab was included in all patients who received chemotherapy. Patient with Primary Burkitt's lymphoma received anthracycline containing combination chemotherapy with high dose methotrexate (RCHOPM) along with intrathecal chemotherapy. 6 of 10 patients who received upfront chemotherapy four achieved partial remission (PR) or complete remission(CR), the rest two were refractory. 2 of 10 patients who received upfront radiotherapy only, one achieved partial PR, the other achieved CR. Of the two patients who were refractory to upfront chemotherapy, one was salvaged with WBRT and is alive after 5 years, the other was lost to follow up. Of two patients who received upfront radiotherapy one was lost to follow up, the other relapsed after nearly 47 months later and was salvaged with Temozolamide and Rituximab, achieved partial remission and is well at the time of analysis. Of the evaluable 8 of 10 patients, at a median follow up of 31 months (range1-66), 6 patients were alive and four without relapse or progression with an overall survival and progression free survival of 75% and 50% respectively. Discussion: To our knowledge this is the first case series of PCNL from Saudi Arabia. All the evaluable patients who received treatment are alive. The results are comparable with other centers, although numbers are small. Strikingly patient who was chemo refractory has shown long term remission to Radiotherapy, which again proves to be a valuable tool in managing these patients. Further studies are needed to define incidence, characteristics and outcomes of these patients from this region.

A-031: Treatment and outcome of elderly patients with Hodgkin's disease: King Fahad Medical City, Riyadh experience

I. Tailor, A. Gill, A. Butt, W. Alshakweer 1 , S. Iqbal, G. Murtaza, I. Motabi, S. Z. A. Zaidi, N. Alshehry, M. Alghamdi, A. Elghazaly, S. Almudaibigh, Y Bayoumi 2

Departments of Adult Haematology/Bone Marrow Transplantation, 1 Pathology and 2 Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia

Background: Hodgkin's disease accounts for approximately 10% of all lymphoma cases. There is paucity of date on outcome of elderly patients with Hodgkin's disease in literature. There is hardly any data from Middle Eastern gulf countries. Materials and Methods: We retrospectively analyzed 168 consecutive patients diagnosed with Hodgkin's disease at our centre from 2006 to 2015 (age >14 years) and found 16 patients to be over the age of 60 years. Results: Out of 16 patients 6 were females, 10 were males and the median age was 70 years (range 61-86).All patients had classical Hodgkin's disease out of which 12 had nodular sclerosis subtype, 2 had mixed cellularity subtype and 1 had lymphocyte rich subtype. 4 patients had early stage disease (IA-IIA) while rest 12 had advanced stage disease. 15 were treated with ABVD based regimen, the other was treated with chlorambucil based regimen.3 out of 16 were given radiation in addition to chemotherapy. Out of the 14 evaluable patients (two were lost to follow-up) 13 completed treatment and all of them achieved complete remission (93%).9 of 16 patients were given reduced dose doxorubicin. Three patients died (one due to sepsis, the other due cardiomyopathy 2 years after treatment, third one due secondary cancer). Of the evaluable 14 patients at a median follow up of 35 months (range 1-72) relapse free survival and overall survival were 75% and 71% respectively. Discussion: As per our study unlike in western world, older patients are less frequently affected with Hodgkin's disease. The remission rates and survival data are very encouraging despite dose reductions, however further data is needed to confirm our results. ABVD with probable dose reductions appears feasible, effective treatment option for elderly patients although frail patients who cannot tolerate ABVD may be candidates for anti CD30 antibody based regimens.

A-032: Molecular monitoring in assessing minimal residual disease and risk of progression in chronic phase CML: our data at King Fahad Medical City

Layla AlSohaibani, Rahaf Altahan, Imran K. Tailor 1 , Ibrahim Motabi 1 , Nawal AlShehri 1 , Abdul A. Peer Zada

Molecular Pathology (Genetics) Section, Pathology and Clinical Laboratory Medicine Administration, 1 Adult Hematology and BMT, King Fahad Medical City, Riyadh, Saudi Arabia

Background: The World Health Organization and European Leukemia Net classification has set up criteria for the definition of the chronic phase (CP), accelerated phase (AP), and blast crisis (BC) of CML. The morphological diagnosis of CP-CML is based on < 10% blasts in peripheral blood and bone marrow, leukocytosis with circulating granulocytic precursors, absolute basophilia, and thrombocytosis. In CP-CML patients on therapy, the reduced disease burden is an important prognostic indicator and minimal response to therapy or relapse suggests a therapy change. Monitoring minimal residual disease in CP-CML in view of its clinical and therapeutic outcome therefore, becomes essential. The standard method for assessing MRD and risk of progression in CML is cytogenetic analysis and qPCR based molecular monitoring of BCR-ABL1 p210. Aim: We sought to assess levels of MRD in CP-CML patients in cytogenetic remission by measuring the levels of BCR-ABL1 p210 fusion gene and assess the progression free survival, and the rate of relapse in our patients. We also assessed the rate of TKI response in CP-CML cases. Methodology: For molecular monitoring in CML, we are using an automated real-time RT-PCR test, the Xpert BCR-ABL (p210) Monitor Assay for quantifying the amount of p210 (b2/a2 and b3/a2) transcript directly from peripheral blood specimens, and the results reported to the International Scale (IS) using a predetermined conversion factor and delta CT-based formula. Cytogenetic analysis (FISH) on bone marrow or peripheral blood samples was used to assess cytogenetic remission (or not) in all CP-CML cases. Results: We describe here 51 CP-CML patients consisting of 29 females (~57%) with a median age of 44 ± 4.9 years (95% CI 26.6-62.39) and 22 males (43%) with a median age of 36 ± 7.7 years. In patients with cytogenetic remission, BCR- ABL1 p210 level was detectable in 30 (30/51, 58.8%) and undetectable (< LOD) in 16 (16/51, 31.3%). 5 patients showed very high levels of p210 either due to relapse, intolerance, or compliance issues. Of the 30 CP-CML patients, 21 (70%) patients revealed BCR-ABL1/ABL ratio < 0.1% IS (MMR) are in continuous remission while 9 (30%) patients showed > 0.1% IS p210 levels and did not achieve MMR. In response to TKI treatment, 48 (94%) CP-CML patients received imatinib as first-line, of whom 35 (72.9%) achieved molecular remission while 13 (27%) revealed treatment failure based on molecular data. Desatinib and nilotinib as second-line were effective in reducing p210 levels (MMR) in patients who failed imatinib treatment. 2 patients received desatinib as first-line and both (100%) achieved molecular remission. 25 (/48, 52%) CP-CML patients showed > 5 years of progression free survival with imatinib with respect to p210 levels (continuous MMR). Conclusion: In summary, depending upon the individual patient co-morbidities, all TKIs (Imatinib, desatinib, Nilotinib) showed good molecular response in CML patients albeit with some degree of intolerance. In CP-CML patients who failed imatinib treatment, desatinib and nilotinib were effective in achieving molecular milestones.

A-033: Molecular monitoring of major BCR-ABL1 isoform p210 by qPCR reveals differential response to tyrosine kinase inhibitors in accelerated phase chronic myeloid leukemia: A case series at KFMC

Rahaf Altahan, Layla AlSuhaibani, Osamah Tawfiq Khoja, Syed Zaidi 1 , Mubarak AlGhamdi 1 , Abdul A Peer Zada

Molecular Pathology (Genetics) Section, Pathology and Clinical Laboratory Medicine Administration, 1 Adult Hematology and BMT, King Fahad Medical City, Riyadh, Saudi Arabia

Background: Chronic myeloid leukemia (CML) patients are characterized by the BCR-ABL1 fusion protein (p210) that leads to a constitutive protein tyrosine kinase activity thereby giving a myeloproliferative phenotype in CML. CML occurs in three different forms: the chronic CP-CML, the accelerated AP-CML and the blast crisis BC-CML, each of which is clinically managed according to standard guidelines (ELN, NCCN) through the use of tyrosine kinase inhibitors (TKIs) such as imatinib, desatinib and nilotinib, bosatinib and ponatinib. In the diagnostic workup, qPCR is considered as the most sensitive and appropriate test for monitoring minimal residual disease (MRD) to define specific therapeutic milestones. Methodology: For molecular monitoring in CML, we are using an automated real-time RT-PCR test, the Xpert BCR-ABL (p210) Monitor Assay for quantifying the amount of p210 (b2/a2 and b3/a2) transcript directly from peripheral blood specimens, and the results reported to the International Scale (IS) using a predetermined conversion factor and delta CT-based formula. Molecular monitoring data were analyzed in relation to TKI response for all the available cases of AP-CML. Results: We describe here seven AP-CML patients of which 6 (~85%) were females (median age 60 years) and only 1 (~15%) male (33 year) for which we performed qPCR. The male patient presented with high SOKAL and HASFORD prognostic risk score, was started with desatinib as first-line and achieved complete cytogenetic remission (negative by FISH) within 3-months of treatment with < 1% levels of p210 by qPCR. He is currently in major molecular remission (MMR, qPCR levels < 0.1% IS). No detectable comorbidities are reported till date. 2/6 (33%) females who received desatinib as first-line also achieved early cytogenetic and molecular response (3-months), and are currently in complete molecular remission (CMR, < LOD at 0.0003% IS). 4/6 (~67%) females who received either imatinib (n = 2) or desatinib (n = 2) as first-line were intolerant or refractory to treatment. Nilotinib (n = 3) and desatinib (n = 1, imatinib refractory case) treatments were able to achieve CMR (n = 3) and MMR (n = 1) in all the patients. The associated comorbidities or toxicities with TKIs observed were mainly hypothyroidism, type II diabetes, vitamin D deficiency, pleural effusion, hemorrhoids, hypercholesterolemia RV dilation and iron deficiency. Conclusion: In summary, depending upon the individual comorbidities AP-CML patients show a differential response to TKIs. In terms of better molecular outcome, desatinib and nilotinib show superior efficacy in AP-CML patients analyzed in this study.

A-034: Quantitative determination of JAK2V617F mutation in myeloproliferative neoplasms by competitive allele specific PCR (cast PCR technology): A validation study at KFMC

Sara Saleh AlSharidah, Rania AlAmri, Abdul A. Peer Zada

Molecular Pathology Section, Pathology and Clinical Laboratory Medicine, Main Hospital King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia

Background: The gain-of-function mutation of the JAK2 kinase, which is a recurrent somatic point mutation (G-C to T-A transversion), at nucleotide 1849 in exon 14, resulting in the substitution of valine by phenylalanine at codon 617 (JAK2V617F), represents a major diagnostic criterion and a clonal marker for myeloproliferative neoplasms such as polycythemia vera (PV), essential therombocythemia (ET) and primary myelofibrosis (PMF). Aim: We aimed to establish the qPCR-based molecular genetic testing methodology for the detection and screening of JAK2V617F mutation in-house at KFMC. In addition we would like to share our experience of quality control procedures used during our validation process in compliance with CAP guidelines. Methodology: We used a methodology based on the amplification technique using Competitive Allele-Specific TaqMan quantitative polymerase chain reaction (castPCR technology) starting with the patient gDNA that is isolated from the whole blood. This mutant allele assay targets key somatic mutation V617F in JAK2 gene and contains an allele-specific primer that detects the mutant allele, a MGB oligonucleotide blocker to suppress the wild type allele, a locus specific primer and a locus specific TaqMan ® FAM™ dye-labeled MGB probe. Results: Using the castPCR methodology, we tested 29 patient specimens for JAK2 V617F at KFMC. Although we successfully obtained the cycle threshold (Ct) values for all the specimens, we evaluated only 21 specimens since 5 were not reported by the reference laboratory, and hence excluded from analysis. The concordance rate of 100% (21/21) was obtained. JAK2 V617F was detected in ~33% of the specimens (7/21) and was undetectable in ~67% (14/21) of the specimens. The specificity, sensitivity, positive and negative predictive values of the assay were all 100%. The delta Ct-cut-off for the wild type and the mutant was 11.6 (95% CI, 18.3-38.9) and 12.5 (95% CI: 15.4-33-4), respectively. The detection limit of the assay is estimated to be 2%. The assay showed a high degree of reproducibility and linearity with the possibility of determining the mutant load (allele burden), but not the zygosity of the mutation. The CAP-PT sample also revealed qualitative compliance. Conclusion: In summary, the castPCR methodology for JAK2 V617F mutation detection is a very reliable, sensitive and a quick method to be used in the clinical service.

A-035: Establishing an optimal qPCR assay based on the International Scale reporting of BCR-ABL1 levels in molecular diagnosis and monitoring of chronic myeloid leukemia at King Fahad Medical City

Abeer AlEnazi, Sara AlZayelee, Sara Al Sharidah, Abdul A. Peer Zada

Molecular Pathology (Genetics) Section, Pathology and Clinical Laboratory Medicine, Main Hospital King Fahad Medical City Riyadh, Kingdom of Saudi Arabia

Background: The formation of the BCR-ABL1 fusion gene is the molecular hallmark of CML. Based on the breakpoint locus in the bcr and abl1 genes, the two main variants have been identified namely the e1a2 (p190 isoform) and the e13a2/b2a2 or e14a2/b3a2 (p210 isoform). The p210 isoform occurs predominantly in CML while the p190 in ALL. Molecular diagnosis and monitoring by qPCR has been identified as the most sensitive technique in the assessment of minimal residual disease, deeper drug response assessment and a means to detect relapse earlier than other methods. Although various guidelines such as the ELN and the NCCN have indicated the need for IS-based reporting of the BCR-ABL1 levels, the main challenge has been the lack of standardized reporting system. This is true particularly for Saudi Arabia, where we send-out tests to different laboratories that report with different scales. Aim: We aimed at establishing the qPCR assay based on the IS reporting system of the BCR-ABL1 levels (p210) in CML in- house at KFMC, and share our experience. Methodology: We used an automated Xpert BCRABL Monitor assay with integrated sample purification, nucleic acid amplification, and target sequence detection. It requires the use of single-use, disposable GeneXpert cartridges that holds and hosts the RT-PCR and PCR reagents and processes. The amount of BCR-ABL transcript is quantified as the ratio of BCR-ABL/ABL and the results reported to the International Scale (IS) using a predetermined conversion factor and delta CT-based formula. Results: We performed qPCR for > 74 specimens that came for BCR-ABL1 p210 molecular testing. Using this assay, we have been able to report BCR-ABL1 levels on the IS system in response to various TKIs achieving major molecular remission (MMR), deep molecular remission (DMR) and/or complete molecular remission (CMR) with a success rate of 100%. any failure rate. The molecular response to treatment was comparable with other laboratory reports as part of our external PT albeit different reporting systems used. The positive and negative predictive value was 100% with 47 detected as true positives and 27 as true negatives. The limit of detection of the assay was estimated to be 0.00037 ± 0.00007 (95% CI, 0.0008-0.001) thereby providing an indication of DMR. The mean Ct value for the control gene ABL was estimated to be 13.7 ± 1.46 (95% CI, 12.74-18.45), and for the fusion gene BCR-ABL1 to be 22.7 ± 2.86 (95% CI, 25.69-36.90). Conclusion: The BCRABL Monitor assay is a reliable method to monitor the p210 (b2a2 and b3a2) translocation in peripheral blood lymphocytes of patients with CML. We propose the standardization of the assay in all the major hospitals of Saudi Arabia in order to uniform reporting system for BCR-ABL1 monitoring of CML for better patient management.

A-036: Prevalence of menstrual cycles and outcome of 50 pregnancies after high-dose chemotherapy and auto-SCT in non-Hodgkin and Hodgkin lymphoma patients younger than 40 years

S. Akhtar, I. Youssef 1 , H. Soudy, T. A. M. Elhassan, S. M. Rauf, I. Maghfoor

King Faisal Specialist Hospital and Research Centre, Oncology Centre, 1 King Faisal Specialist Hospital and Research Centre, Nursing Affairs, Riyadh, Kingdom of Saudi Arabia

Data are limited regarding the prevalence of menstrual cycles and pregnancies after high-dose chemotherapy (HDC) and auto-stem cell transplantation (SCT). Female patients who underwent HDC auto-SCT for non-Hodgkin and Hodgkin lymphoma (1997-2012) were reviewed. The selection criteria were as follows: (1) alive without disease 12 and 24 months after auto-SCT for menstrual cycles and pregnancy, respectively, (2) age o40 years at auto-SCT, and (3) no primary infertility. One-hundred and seventy-six females underwent single auto-SCT. Eighty-nine were eligible for menstrual cycles and pregnancy analysis. Median age at auto-SCT was 25 years (14-40 years), at pregnancy 27 years (20-37 years), median follow-up 65 months (range 24-190). Regular menstrual-cycles resumed in 56/89 patients (63%). Increasing age (P = 0.02) and number of prior chemotherapy cycles (P = 0.02) are associated with higher risk of amenorrhea. Forty patients tried to get pregnant, 26 (65%) became pregnant 50 times: 43 (86%) live birth, 7 (14%) miscarriage and 2/50 had birth defects. Twenty-four patients practiced breastfeeding (median duration 4 months (1-24 months)). Enough breast milk production was reported 62.5% vs 100% in those patients who did or did not receive above the diaphragm radiation therapy, respectively, (P = 0.066). Our data highlights significantly higher than perceived incidence of menstrual cycle resumption, successful pregnancies and breastfeeding after HDC auto-SCT.

A-037: Fertility recovery following allogeneic bone marrow transplantation in aplastic anemia; a study of 157 patients

Feras Alfraih, Shad Ahmed, Dennis (Dong Hwan) Kim 1 , Ghuzayel Aldawsari, Fahad Alsharif, Said Yousuf Mohamed, Walid Rasheed, Amr Hanbali, Syed Osman Ahmed, Marwan Shaheen, Fahad Almohareb, Mahmoud Aljurf, Naeem Chaudhri, Hazzaa Alzahrani

Department of Oncology, Hematology and Allogeneic Bone Marrow Transplant Program, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia, 1 Department of Medical Oncology and Hematology, Allogeneic Blood and Marrow Transplant Program, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada

Introduction: Infertility is a major late effect of hematopoietic stem cell transplants (HSCT). In aplastic anemia (AA) patients, although the fertility recovery rate is relatively higher than other diseases but the exact incidence and risk factors are not very well studied. In this study, we attempted to evaluate incidence and the impact of patient's characteristics and transplantation procedures on fertility recovery following allogeneic HSCT for adolescent and adults patients with AA. Methods: A total of 157 patients who were at least 14 years old with AA receiving HSCT between year 1987 and 2014 at our center were reviewed. Patients who survived at least 2 years following HSCT and either married or in relationship were included in the analysis and evaluated for fertility following HSCT. 87 patients were eligible for the study. Questionnaire survey and long-term charts were used for data collection. With a response rate and or available information of 63% patients, 55 patients were identified and stratified into fertility recovery (FR+) versus non-fertility recovery (FR-) group. Fertility recovery was defined by a pregnancy of the patient or his partner. Results: Median age for all patients is 23 years (range, 14-50), 44% (n = 24) between 14-20 years old, 51% (n = 28) between age 20-40 years and 5% (n = 3) > 40 years. 51% (n = 28) were females. Matched related donor was used for majority of patients 96% (n = 53). GVHD prophylaxis was CSA/MTX for 93% (n = 51). Conditioning regimen was Cyclophosphamide/Flu in 25 (45%), Cyclophosphamide/ATG in 18 patients (35%) and others in 12 patients (20%). Bone marrow was the source of stem cells for 52 patients (94%). A median follow-up of 8 years for survivors (range, 0.3-23) showed 45 patients (82%) had FR + while 10 patients (18%) were FR-. Median duration of fertility recovery (from delivery to BMT) was 6 years (range, 0.8-19) with significant difference based on age groups, 4 years for patients 20-40 years (n = 29, 53%) versus 8 years for those < 20 years (n = 24, 44%), (P = 0.002), [Figure 1]. None of the patients > 40 years old (n = 2, 4%) had fertility recovery. Comparison based on gender showed no significant difference. Males had a median duration of fertility recovery of 5.9 years, (range 0.6-14.9) versus 6.2 years, (range, 0.8-15.2) (P = 0.31) females. The overall median number of pregnancies was 2 (range, 1-6). For males, it was 2 (range, 1-6) while 1.5 (range, 1-5) for females (P = 0.26). Deliveries occurred in natural ways in (95%) while C-section for (5%). All deliveries were without fetal abnormalities. Univariate analysis of risk factors for fertility recovery showed age group (P = 0.03) and chronic GVHD (P = 0.05) are important factors. Neither gender of patients or type of preparative regimens used for HSCT (Cyclo/ATG vs Cyclo/Flu) was a risk factor. In multivariate analysis, age group was the only confirmed an independent risk factor for fertility recovery (P = 0.02) [HR = 2.02, CI = 1.012-3.64). Conclusion: The present study suggested that the incidence of fertility recovery following HSCT for patients with aplastic anemia is high with no significant differences between males and females. Patients between the ages of 20-40 years at the time of HSCT have significantly shorter recovery period. Age was the only independent risk factor for fertility recovery while there was no impact of whether ATG or Fludarabine was used in addition to Cyclophosphamide as preparative regimen.



A-038: Impact of anti-thymocyte globulin to post-transplant high dose cyclophosphamide in the outcome of haploidentical hematopoietic stem cell transplantation in patients with high risk hematological malignancies

Ghuzayel M. Al Dawsari, Said Mohamed, Fahad Almohareb, Naeem Chaudhri, Fahad Alsharif, Hazzaa Alzahrani, Walid Rasheed, Amr Hanbali, Marwan Shaheen, Feras Alfraih, Tusneem Elhassan, Mahmoud Aljurf

Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Background: Historically, Haploidentical HSCT has been complicated by unacceptable high incidences of graft rejection, severe graft-versus host disease (GVHD) and nonrelapse mortality (NRM). Haploidentical HSCT with modern approach with post-transplant high dose cyclophosphamide becomes an attractive approach with promising results. However, GVHD remain a major obstacle in our series when compared with published literature, for which a small dose of ATG was added to PT-CY approach in haploidentical HSCT. Methods: Analysis of patient's data with who underwent Haploidentical HSCT in prospective phase II study from January 2013 to November 2015. Eligibility criteria include patients with high risk hematological malignancies, less than or equal to 50 years of age without a suitable matched related donor, lack of fully matched unrelated donor(MUD) and Karnofsky performance of 70-100%. Donor selection criteria include age of 18 years or more, a maximum 5 antigen mismatched is accepted and donor were excluded if the recipient ' serum contain anti-donor HLA antibodies. Myeloablative conditioning regimen consisted of total body irradiation (TBI) and fludarabine or thiotepa, busulfan and fludarabine (TBF). GVHD prophylaxis consist of PT-CY (50 mg/Kg) on day + 3 and + 5 and cyclosporine (+4 to +180) and mycophenate mofetil for 28 days. ATG/Genzyme 1.5 mg/Kg was given on day-2 and-3 for the last 10 patients in order to further reduce acute GVHD. Result: A total of 21 patients received haploidentical HSCT, ATG were added to the protocol after 10 patients. Patients characteristics are shown in Table 1, with a median follow up of 3.5 (range, 1-9) for the ATG group and 14 months (range, 8.5-16) months for group with no ATG. The median time to both neutrophil and platelet (ANC > 0.5 × 109/L; platelet > 20 × 109/L) engraftment were (ANC 16; platelet 35) and (ANC 18.5; platelet 28) days for ATG and NO ATG group respectively. Graft failure was o in both groups. The 100-daycommutative incidence (CI) of grade II-IV acute GVHD was 0.1 and 0.55% for ATG and NO ATG group respectively. CI of chronic GVHD was 0 and 0.27 (P = 0.04) for ATG and NO ATG group respectively. The CI of relapse was 0.34 and 0.27% for ATG and NO ATG group respectively. Summarize the outcome and complication of both groups. Conclusion: Haploidentical HSCT represent a good alternative option for patients with high risk hematological malignancies who do not have suitable HLA-matched donors as it provide good engraftment of ANC and PLT and good OS rate in patients with high risk hematological malignancies. The addition of ATG to PT-CY provides areseanable approach to further control acute GVHD, with possible effect on immune reconstitution, which will be evident with longer follow up.



A-039: Cytomegalovirus infection in children after bone marrow transplantation: Risk factors, clinical aspects and outcomes

Muhammad Matloob Alam, Mohamed Bayoumy, Areej Ali, Muayad Alali, Bayanah Al-Enezi, Ibraheem Abosoudah

Department of Oncology, Section of Pediatric Hematology/Oncology and Blood and Marrow Transplant, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia

Background: Cytomegalovirus (CMV) infection remains the most common and potentially severe viral complication in patients given hematopoietic stem cell transplantation (HSCT). The aim of this study was to determine the incidence, risk factors and outcomes of CMV infection in pediatric BMT unit. Materials and Methods: This is a single-center, retrospective study, we analyzed the records of 131 pediatric patients who underwent BMT to determine the incidence of CMV infection/reactivation and disease and to identify the important risk factors, clinical aspects and outcomes of CMV infection/reactivation in post BMT pediatric patients at our tertiary health care facility. Results: The mean age of the study population was 6.5 ± 4 years. Out of males were 85 (64.9%). Majority of patients have hematological disorder/malignancy (n = 101; 77%) followed by solid tumors (n = 30; 23%). Most patients received allogeneic transplant (n = 92; 70.2%). CMV reactivation was observed in 38 (29%) patients, out of them only (n = 3; 2.3%) had clinical manifestation/organ involvement and most cases of CMV were resolved (n = 35; 26.7%). Benign hematological disorder, conditioning regimen containing ATG, allogeneic BMT, GVHD prophylaxis used and development of GVHD were identifiable risk factors in all patients and lymphopenia <300/mm 3 (P = 0.047) were the only identifiable risk factors in allogeneic BMT patients associated with development CMV reactivation [Table 2]. There is no difference in engraftment failure in patients who had CMV reactivation and no CMV reactivation 18.5% vs. 16% [P = 0.75; OR 1.2 (CI, 0.437-3.157)], however patients who had CMV reactivation had significantly higher rate of GVHD as compared to patients without CMV reactivation (12/38 = 31.6%) vs 14/93 = 15.1%) [P = 0.031; OR 2.6 (CI, 1.07-6.34)]. Other outcome variables including relapse rate (8/38 = 21% vs. 24/93 = 25.8%) [(OR: 0.8; 95% CI: (0.31-1.91)] and mortality rate 9/40 = 22.5% vs. 31/93 = 33.3% [(OR: 0.7; 95% CI: 0.29-1.63)] in patients with CMV reactivation versus no CMV reactivation respectively, were not statistically significant. Overall survival and event free survival of patients with and without CMV antigenemia were also comparable. Conclusions: In conclusion, advances in the control of CMV infection after SCT have had a great impact on the improvement in transplant outcomes. Our study showed the effectiveness of antigenemia-guided pre-emptive strategy with ganciclovir in our cohort and that the prognosis for those who developed antigenemia was not significantly poorer than was the prognosis for those who did not, while development of CMV disease tended not to affect the outcome. However high reactivation is associated with development of CMV disease and there is significant association between development of CMV antigenemia and disease and acute GVHD, indicating an urgent need for the establishment of an optimum pre-emptive strategy based on the severity of acute GVHD.



A-040: BK virus-associated hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation; incidence and risk factors

Amjad Alhussaini, Farhan Anjum 1 , Ghuzayel Aldawsari 1 , Fahad Alsharif 1 , Said Y. Mohamed 1 , Walid Rasheed 1 , Amr Hanbali 1 , Syed Osman Ahmed 1 , Marwan Shaheen 1 , Riad El fakih 1 , Hazzaa Alzahrani 1 , Naeem Chaudhri 1 , Fahad Almohareb 1 , Mahmoud Aljurf 1 , Feras Alfraih 1

College of Medicine, Almaarefa Colleges for Science and Technology, 1 Department of Oncology, Hematology and Allogeneic Bone Marrow Transplant Program, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia

Introduction: Hemorrhagic cystitis (HC) is one of the common complications after allogeneic hematopoietic SCT (HSCT) with reported incidence varying from 7 to 70%. Several reports have shown that BK is strongly associated with HC (BK- HC) following HSCT. We conducted an institutional retrospective study to analyze the incidence and clinical factors associated with BK-HC following HSCT. Methods: A total of 517 consecutive patients above the age of 14 years receiving HSCT from 2009 and June 2015 were included in this retrospective analysis and evaluated for HC and urinary BK. HC was defined as documented hematuria of any grade and BK viruria defined as positive at any level by BKV quantitative PCR testing in urine. Patients were stratified, based on hematuria and urinary BK virus, into the following groups (a) BK virus positive hemorrhagic cystitis (BK + HC), (b) BK virus negative hemorrhagic cystitis (BK-HC) and (c) Non-hemorrhagic cystitis (HC-) group. Screening for microscopic hematuria was performed only for patients with any kind of urinary symptoms. Results: 479 patients (92.6%) were matched related donor and 308 (60%) were male with a median age of 24 (range 14 to 66). Diagnoses were AML for 195 (38%), ALL for 183 (35%) and bone marrow failure for 44 (8.5%). Conditioning regimen was cyclophosphamide based in 427 (82.6%) patients (97%) versus others in 90 (17.4%) patients. GVHD prophylaxis was CSA/MTX for 456 (88.4%) however, T cell depletion was used in 13%. Peripheral blood stem cells were used for 56% of patients. With a median follow-up of 60 months for survivors (range 2-116.5 months), 43 patients (8%) showed BK + HC, 264 (51%) BK-HC while 209 (41%) did not have any hematuria (HC-group). Median time from transplantation to BK + HC was 67 days (range 7-1261 days). Univariate analysis for risk factors of BK + HC showed male, use of T-cell depletion and AML diagnosis were statistically significant factors. Other factors like age, conditioning regimen, GVHD prophylaxis, stem cell source, mismatched and remission status were not statistically significant. BK + HC group was associated with higher incidence of other infections like CMV viremia (P = 0.01) and fungal infection (P < 0.01). Incidence of acute GVHD was 62.8% in BK + HC group, 43% in HC-BK and 33.3% in HC-group (p=<0.01), suggesting higher incidence of acute GVHD in BK + HC group. There was no difference in incidence of chronic GVHD. Conclusion: Hematuria following allogeneic bone marrow transplantation occurs in almost half of patients (51%) while BK associated HC develops in 8% of patients. Factors associated with BK + HC were male gender, use of T-cell depletion and AML diagnosis. Further studies are needed to minimize or prevent BK + HC following HSCT especially in high risk group.

Key words: BK virus, hematopoietic cell transplant, hemorrhagic cystitis

A-041: Influence of matched sibling Donor's availability and stem cell transplantation on treatment outcome for acute lymphoblastic leukemia; study on 294 patients

Feras Alfraih, Wahiba Chebbo, Dennis (Dong Hwan) Kim 1 , Ghuzayel Aldawsari, Fahad Alsharif, Hazzaa Alzahrani, Said Yousuf Mohamed, Walid Rasheed, Amr Hanbali, Syed Osman Ahmed, Marwan Shaheen,

Naeem Chaudhri, Fahad Almohareb, Mahmoud Aljurf

Department of Oncology, Hematology and Allogeneic Bone Marrow Transplant Program, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia, 1 Department of Medical Oncology and Hematology, Allogeneic Blood and Marrow Transplant Program, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Canada

Introduction: Predicting treatment outcome of acute leukemia has been an important issue. Many factors have been elucidated. We evaluated the impact of donor's availability on treatment outcome including mortality in patients with acute lymphoblastic leukemia (ALL). Methods: A total of 294 patients with ALL were evaluated after receiving chemotherapy between year 2001 and July 2014 at our center. Patients were assessed for the need of hematopoietic stem cell transplants (HSCT), availability of HLA sibling match donor and the impact on overall outcome. Indications for transplantation were defined based on our center's policy that has been shown in previous publications. Patients were divided into 3 categories, group A with an indication for HSCT and available donor (HSCT+/D+), group B with HSCT indication but no available donor (HSCT+/D-) and group C with no indication for HSCT regardless of donor status (HSCT-). Results: The median age was 20 (14-63 years). 95 (32%) were female while 198 (68%) were male. 276 (86%) patients were newly diagnosed while 18 (14%) were relapsed. Immuno-phenotype was B for 191 (65%), T for 91 (31%) versus mixed lineage for 12 (4%). 33 (11%) patients were positive for Philadelphia chromosome. Median WBC at diagnosis was 23.2 × 109/L CNS involvement was positive in 26 (8%) patients. With a median follow-up of 60 months for survivors (range 2-116.5 months), the 3-year OS for HSCT+/D-, HSCT+/D+ and HSCT-were 39%, 57% and 55% (P < 0.001), [Figure A] while DFS was 25%, 44% and 44% (P = 0.004) for group A, B and C, respectively. No statistical significance difference was noted on NRM between the groups. Conclusion: Our study suggested that unavailability of donor is an independent risk factor on OS and DFS. The use of alternative donor and building national/regional unrelated donor registry is highly warranted even in countries with high probability of finding matched sibling donor.



A-042: Impact of GCSF primed bone marrow on outcome of allogeneic hematopoietic stem cell transplantation in adolescent and young adult with severe aplastic anemia

Ghuzayel M. Al Dawsari, Walid Rasheed, Said Mohamed, Hazzaa Alzahrani, Fahad Almohareb, Naeem Chaudhri, Fahad Alsharif, Amr Hanbali, Syed Osman Ahmed, Marwan Shaheen, Feras Alfraih, Tusneem Elhassan, Mahmoud Aljurf

Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Background: Steady state bone marrow (SS-BM) is the standard source of hematopoietic stem cell in allogeneic hematopoietic stem cell transplant (HSCT) from related sibling donor in patient with severe aplastic anemia (SAA). However, the use of G-CSF Primed bone marrow (G-BM) as a stem cell source is usually limited and only considered in transplant practice in the presence of major ABO-incompatibility (requiring red cell depletion) or significant difference in the weight between the donor and recipient in an attempt to obtain adequate SC dose engraftment without increasing the risk of graft versus host disease. Here, we report our center's experience of HSCT as the first cohort in adolescent and young adult patients with SAA with and without G-BM with long term follow up. Method: We retrospectively evaluated outcomes in adolescent and young adult patients underwent allogeneic HSCT for SAA from January 2002 to June 2014 with G-BM as stem cell source and compared it with same time cohort control group who received SS-BM. Results: A Total of 23 patients (study group) received the marrow graft primed with G-CSF 5 μg/Kg/day for 4 days before marrow harvest, and 59 patients (cohort control group) received marrow graft without G-CSF priming. Patient's characteristics were comparable in both groups and are shown in Table 1, with a median follow up of 72 months (range, 19-115). All donors were related HLA-identical siblings except for two patients who had one antigen mismatched sibling donors. Conditioning regimen was CY/ATG from January 2002-June 2004 and FLU/ATG from July 2004 to June 2014. All patients received the same graft-versus-host disease (GVHD) prophylaxis (Cyclosporine and Methotrexate). The median time to both neutrophil and platelet engraftment (ANC >0.5 × 109/L; platelet >20 × 109/L) were comparable in both group, at 21 versus 20 day and 25 versus 22 days in the G-BM and the SS-BM groups respectively. No graft failure was reported in the G-BM group with 8.5% cumulative incidence in SS-BM group (P = 0.1). The incidence of grade II-IV acute GVHD was not statistically different, 13.6% in the G-BM group and 23.8% in the SS-BM group (P = 0.1). Chronic GVHD was significantly lower in the G-BM group (5%) compared to SS-BM (26.3%) (P = 0.04. Overall survival rates (91.3% versus 80.6%) between the primed and unprimed marrow group. Conclusion: G-CSF mobilized bone marrow is a reasonable stem cell source in patients with SAA and Major ABO incompatibility or significant donor/recipient weight discrepancy, resulting in comparable engraftment with no reports of graft failure in this series and no increase in GVHD risk in comparison to SS-BM source. The above observation should be further tested in larger prospective trial as the optimal stem cell source in patient with severe aplastic anemia after HLA-identical related HSCT.



A-043: Outcome of second myeloablative allogeneic hematopoietic stem cell transplantation from matched related donors for patients with acute leukemia: Single institution experience

Amr Hanbali, Noura Alhashim, Syed Osman Ahmed, Fahad Almohareb, Fahad Alsharif, Naeem Chaudhri, Said Y. Mohamad, Hazza A. Alzahrani, Walid Rasheed, Ghuzayel Aldawsari, Marwan Shaheen, Feras Alfraih, Riad Alfaqih, Mahmoud Aljurf

Adult hematology/HSCT, King Faisal Specialist Hospital, Riyadh, Saudi Arabia

Introduction: Relapse in patients with acute leukemia following allogeniec stem cell transplant (allo-SCT) continues to be a major cause of mortality. Second allo-SCT might provide an effective salvage therapy for such patients. The aim of this study is to evaluate the outcome of second myeloablative allo-SCT (SCT2) from matched related donors in patients with acute leukemia relapse after their first allo-SCT (SCT1). Materials (or patients) and Methods: We identified 21 patients aged 5-41 (median 20 years) with acute leukemia (both AML and ALL), who underwent a second myeloablative allogeneic stem cell transplantation (SCT2), from matched related donors for relapsed acute leukemia following a first allo-SCT (SCT1) between 1988 and 2010 at King Faisal Specialist Hospital and Research Center in Riyadh, KSA. Data regarding patients' characteristics, type of leukemia at diagnosis, disease status at the time of SCT1 and SCT2, source of stem cells (bone marrow vs. peripheral blood), conditioning regimens, GVHD prophylaxis, chronic GVHD data for both the first and second allogeneic transplants were collected. Results: Of the 21 patients who were evaluated, 76% were males. 13 patients had AML, 5 had B-ALL, 2 had T-ALL and 1 had biphenotypic acute leukemia. With a median follow-up of 11 months post SCT2, 1- and 2-year progression-free survival (PFS) was 61%% and 31% respectively, and 1- and 2-year overall survival (OS) rates were 60%% and 30%% respectively. The median PFS and median OS following SCT2 was 17 (95% CI: 9-25) months and 14 (95% CI: 10-22) months respectively. PFS and OS were significantly lower in patients who relapsed before 24 months from SCT1 and in complete remission prior to SCT2. OS for patients relapsed within 2-years of SCT1 was 12.5% compared to 41.5% for patients relapsed after 2-years, P value = 0.03. PFS was 12.5% vs. 43.5%, P = 0.01 for patients relapsed within 2-years and after 2-years respectively. Conclusion: Survival post allo-SCT relapse in acute leukemia remains limited. The results of this study demonstrate that second myeloablative SCT from related donors could provide a relatively long-term disease free and overall survival in acute leukemia patients who relapsed after first myeloablative SCT. Patients who relapsed after 24 months from SCT1 had a greater benefit from SCT2.

A-044: Young adult patients with post-hematopoietic cell transplantation relapse of AML may benefit from aggressive salvage and 2nd cellular therapy

Syed Osman Ahmed, Amna Gamil 1 , Muhamad Hitham Almahayni, Naeem A. Chaudhri, Fahad Alsharif, Said Y. Mohamad, Hazza A. Alzahrani, Walid Rasheed, Ghuzayel Aldawsari, Amr Hanbali, Marwan Shaheen, Feras Alfraih, Shad Ahmed, Khaled Ibrahim, Fahed Almhareb, Mahmoud Aljurf

Adult Hematology/HSCT, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia

Introduction: There is currently no standard of care for patients with AML who relapse following hematopoietic cell transplantation (HCT), and outcomes in these patients are generally poor. Given this fact, there is great variability in practice, and many patients may be palliated in the absence of suitable clinical trials, especially following early relapses. We sought to analyse long-term survival of young adults with AML based on whether or not they received a second cellular therapy (CT) (second transplant or donor lymphocyte infusion [DLI]) following post-HCT relapse. Methods: We retrospectively analysed data on patients who had received a HCT between 2000 and 2012 and had a post HCT relapse. The patients were stratified by whether or not they had 2 nd CT with or without prior chemotherapy. Baseline characteristics and outcomes were compared. Results: Ninety four patients were identified who had relapsed AML following HCT. The median age at transplant for the patients was 27.5 (range 14-58 year) years for the whole cohort; 50% were females. Of these, 30 patients received 2 nd CT either in the form of DLI (80% for available CT data) or a 2 nd HCT. Median in age for both groups was 24 years and there was no significant difference between the 2 groups in good or poor risk cytogenetics. Median time to relapse was significantly lower in the group that did not receive 2 nd CT vs. the group that did (5.9 vs. 18.2 months, P < 0.001). For the 64 patients that did not receive 2 nd CT, reasons included early relapse (28 cases), presence of GVHD (15 cases), refractory to salvage (8 cases), poor performance (9 cases), and patient choice (4). The OS for patients who did not receive 2 nd CT was 4.5 months ± 2.6% vs. 36% ±11% for patients who did receive 2 nd CT [Figure 1]. Of the 6 patients in the 2 nd CT group who relapsed in < 6 months, only 1 survived long term (16%). Conclusion: The management of post BMT relapse remains challenging, and a number of factors may preclude intensive therapy post-HCT relapse. However, our experience confirms that a proportion of patients do benefit from long-term survival from a strategy of aggressive salvage followed either by DLI or a second HCT; in addition to disease biology, a treatment bias where early relapses are less likely to be treated aggressively partly explains the difference in outcome in the groups. This strategy should be considered in young fit patients and may lead to long-term survival in a significant proportion of young adults; patients with later relapses beyond 6 months appear to derive a greater benefit. Prospective clinical trials are required incorporating novel therapies in patients who relapse early post HCT.



A-045: High-dose chemotherapy and autologous stem cell transplantation for relapsed or refractory nodular lymphocyte predominant Hodgkin lymphoma

S. Akhtar 1 , T. A. M. Elhassan 1 , W. Edesa 1],[2 , M. S. Rauf 1 , M. N. Zahir, I. Maghfoor

1 King Faisal Specialist Hospital and Research Centre, Oncology Centre, Riyadh, Kingdom of Saudi Arabia, 2 Department of Oncology,

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma. We report our results of relapsed/refractory NLPHL patients who received high-dose chemotherapy and autogenic stem cell transplantation (HDC auto-SCT). Seventeen NLPHL patients received HDC auto-SCT (1996-2014): male 14 and female 3, with median age at diagnosis of 22 years, at HDC auto-SCT 28 years (15-58 years). At the time of relapse/progression, 13 (76%) had NLPHL and 4 (24%) had transformed diffuse large B cell lymphoma. The reason for HDC auto-SCT was refractory NLPHL in 12 patients and relapsed in 5 patients. Salvage chemotherapy was etoposide, methylprednisolone, cisplatinum, and Ara-C (ESHAP); eight patients also received rituximab with ESHAP. HDC was carmustine, etoposide, cytarabine, and melphalan (BEAM). Post-auto-SCT, complete remission was achieved in 14 (82%), partial remission in 1 (6%), and progressive disease in 2(12%) patients. The median follow-up is 63 months from auto-SCT (6-124 months). Of the nine patients who received only ESHAP, four had post-auto-SCT events versus no event in all eight patients who received rituximab + ESHAP. Kaplan-Meier estimates of 5-year event-free survival for the whole group is 76%: rituximab + salvage (100%) versus salvage alone (56%), P = 0.041. Overall survival is 94%: 100 versus 89%, respectively, P = not significant (NS). Even in refractory NLPHL patients, long-term disease-free survival is possible after HDC auto-SCT. Post-auto-SCT relapse or progression can still be managed with chemo/chemo+immunotherapy/radiation. These encouraging results of rituximab in salvage setting should be explored further in a clinical trial setting for this patient population.

Key words: Autologous stem cell transplantation, ESHAP chemotherapy, nodular lymphocyte predominant Hodgkin lymphoma, Hodgkin lymphoma, refractory Hodgkin lymphoma, rituximab-containing salvage

A-046: Outcome of hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation using (fludarbine/melphlan/ATG): Single center experience

Muayad Alali, Muhammad Matloob Alam, Mohamed Bayoumy, Ibraheem Abosoudah

Department of Oncology, Section of Pediatric Hematology/Oncology and Blood and Marrow Transplant, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening syndrome of excessive immune activation. The introduction of Hematopoietic stem cell transplantation (HSCT) has dramatically improved HLH patient's survival, however, the optimal conditioning regimen for HLH is still debated. Methods: We retrospectively reviewed the outcome of 10 HLH patients who underwent allogeneic HSCT using reduced intensity conditioning (RIC) comprised of Fludarbine/Melphlan/ATG at King Faisal Specialist Hospital and Research Center-Jeddah between January 2010 and March 2014. Results: There were 7 (70%) males. The median age at presentation was 19 months (range 0.18-7.2 years), the median time to HSCT was 5 months (range 0.19-0.8 years). Family history of HLH was positive in (60%), consanguinity were present in (70%). Genetic mutations were found in (80%) of patients, 2 cases (STX11), one case (UNC13D), one case (STXBP2), 2 cases of Chediak-Higashi (LYST) and one case of XLP1 (SH2D1A). Central nervous system disease was present in (30%) of cases. Bone marrow hemphagocytosis was documented at diagnosis in (70%) of cases. HLH activity prior to HSCT was controlled in all patients but one. She reactivated after HSCT and family refused second transplant, unfortunately she succumbed to her disease. The average CD34 dose was 7 × 106/kg. All patients engrafted, the median time of neutrophil and platelet recovery were at day 14 and 7 respectively. Graft-versus-host disease was observed in (40%), grades II to III (30%).CMV reactivation occurred in (50%). Post-transplantation mixed chimerism was observed in (30%).There was no transplant related mortality. The overall and event free survivals after HSCT were (90%). Conclusion: The outcome of Fludarbine/Melphlan/ATG conditioning in this cohort of patients shows promising results. However, large cohort multi-center prospective studies are needed to validate the effectiveness and long-term survival this regimen.

A-047: Hematopoietic stem cell transplantation in adolescent and young adults with fanconi anemia is feasible with acceptable toxicity, with those surviving 100 days posttransplantation having excellent outcomes

Ahmad Alhuraiji, Hazza Alzahrani, Fahad Al mohareb, Naeem Chaudhri, Fahad Alsharif, Said Mohamed, Walid Rasheed, Ghuzayel Aldawsari, S. O. Ahmed, Mahmoud Aljurf

Department of Oncology, Hematology/HSCT section, MBC 64, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia

Background: Fanconi anemia (FA) is a congenital bone marrow failure syndrome (BMF) that is associated with congenital anomalies and an increased risk of cancer. Hematopoietic stem cell transplantation (HSCT) is a potentially curative modality for BMF in FA patients. Here we report our centre's experience of adolescent and young adults (AYA) FA and HSCT. Materials and Methods: Retrospective analysis of patients' data from patients' charts and electronic system from 1988 to 2013. We included patients with confirmed FA based on positive chromosome breakage study aged 14 years or older underwent HSCT at our institution. Results: A total of 12 patients with FA who underwent HSCT in our institution have been included in the study. The median age was 20 years (Range 14-31 year) with a female predominance of 83%. Low dose cyclophosphamide (Cy) 20-80 mg/kg based conditioning regimens have been used with different combination either fludarabine (Flu), AntiThymocyte globulin (ATG) or total body irradiation (TBI). All patients had HLA matched sibling grafts. In all patients, stem cell source was the bone marrow. All patients engrafted. Four patients (33%) developed acute graft versus host disease (GvHD). Three (25%) patients died early before day + 100 post HSCT due to infectious complication, one of them with steroid refractory acute GvHD. Overall survival was 75% at a median follow up of 43 months. All patients who survived are well and remained transfusion independent without evidence of secondary malignancy. Conclusion: Our findings support the feasibility of reduced intensity conditioning allogeneic HSCT in older and more heavily pre- treated patients with FA especially for those who engrafted.

A-048: Bone marrow transplantation in children: A single-centre experience in Saudi Arabia

Muhammad Matloob Alam, Ibraheem Abosoudah, Shara AL Harbi, Marwa Elhadidy, Areej Ali, Mohamed Bayoumy

Department of Oncology, Section of Pediatric Hematology/Oncology/BMT, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia

Introduction: Bone Marrow Transplantation (BMT) has frequently considered as a curative treatment for children with serious hematological and malignant disorders. The aim of this study was to determine the indication, frequencies of transplant-related morbidity and outcome at our tertiary health care facility. Materials and Methods: We retrospectively analyzed the clinical, laboratory and outcome data of all 131 pediatric patients consecutively underwent BMT between 2005 and 2014. Results: The mean age of the study population at the time of transplant was 6.5 ± 4 years. Out of them males were 85 (64.9%) and females were 46 (35.1%). Majority of patients have hematological nonmalignant disorder (n = 51, 38.2%) followed by hematological malignancy (n = 50; 38.2%); then solid tumors (n = 30; 22.8%). Most of the patients received allogeneic transplant (n = 92; 70.2%) and remaining (n = 39; 29.8%) were autologous transplant. Source of donor in all allogeneic cases were full matched related donor. Source of stem cell in (n = 51; 38.9%) patients was bone marrow and (n = 43; 32.9%) was peripheral stem cell. Mean stem cell dose CD 34 was 7.2 (±0.25) x 106/kg. Acute GVHD was observed in 26 (19.8% in all and 28.3% in allogeneic transplant patients). Out of them grade I, II, III and IV GVHD were observed in 9, 10, 5 and 2 patients respectively. Chronic GVHD was observed in 9 (6.9%) cases. Most of patients were engrafted (n = 109; 83.2%) with median duration of ANC engraftment is 20.9 (Range: 9-48) days and median platelet engraftment days of 28 (Range: 7-200) days. CMV reactivation was observed in 38 patients (29%) cases within 100 day of post BMT. Out of them majority were asymptomatic (n = 35; 26.7%) and remaining (n = 3; 2.3%) had clinical manifestation/organ involvement (retinitis/pneumonia/colitis/hepatitis and skin manifestation). Most of CMV cases were resolved (n = 35; 26.7%). In most case (35/38; 92.1%), the level of antigenemia declined within 2 weeks as a result of the continuation of GCV therapy, but only three out of 38 patients subsequently developed CMV disease. There is no difference in engraftment failure in patients who had CMV reactivation and no CMV reactivation 18.5% vs 16%, however patients who had CMV reactivation had significantly higher rate of GVHD as compared to patients without CMV reactivation (12/38 = 31.6%) vs 14/93 = 15.1%) [P = 0.031]. Overall survival (OS) and Event free survival (EFS) rate were 69.5% and 75.6% respectively. Overall survival time was 35.5 (±2.8) months and EFS time is 31.6 (±2.6) months with mean duration of follow up 72 (±4.4) months. Cause of death in majority of patients (31/40) were either progressive disease and/or relapse, however in other 9 (9/40 = 6.9%) patients who died in remission the possible causes of death were as follow (5 sepsis, 3 GVHD and/or VOD, 1 secondary pulmonary fibrosis). Conclusion: In conclusion, recent development in better understanding of GVHD, process of engraftment and advances in the field of infection control after BMT have had a great impact on the improvement in transplant outcomes. The results of the pediatric BMT program at our institution have been comparable to those reported in the literature as far as transplant-related morbidity and mortality is concerned. The duration of follow-up is short and the long-term outcome is yet to be determined.

A-049: Improving the sensitivity of supervised machine learning algorithms in predicting the odds of day-100 treatment related mortality in acute and chronic leukemia patients post allogeneic stem cell transplantation using different sampling techniques: An example of imbalance classification problem, 1042 cases

Tusneem A. Elhassan, N. Chaudhri, Ghuzayel Aldawsari, Fahad Alsharif, Hazzaa Alzahrani, Said Yousuf Mohamed, Walid Rasheed, Amr Hanbali, Syed Osman Ahmed, Marwan Shaheen, Feras Alfraih, Riad Elfakih, Fahad Almohareb, Mahmoud Aljurf

Department of Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Introduction: Day-100 treatment related mortality (Day-100 TRM) is one of the important measures of allogeneic stem cell transplantation (ALLO-SCT) outcomes. However, predicting the odds of Day-100 TRM using machine learning (ML) classification algorithms is faced with some challenges due to the imbalance distribution of this event (TRM vs. No TRM) among the studying data set. Building a predictive model for this type of data results in a model with a low sensitivity towards the minority class yet high overall accuracy and specificity. This is because most the ML classification algorithms are built with an ultimate goal of improving the overall accuracy. Sampling the training data set to produce a balanced distribution of the class categories is one of the suggested solutions to overcome this problem. Materials (or Patients) and Methods: Different sampling techniques such as Random Oversampling (ROS), Random Under sampling (RUS) and Synthetic-oversampling technique (SMOTE) were utilized to improve model sensitivity towardst he minority class (Day-100 TRM). A guided under sampling using Tomek link (TLink) was also utilized as a data cleaning method followed by the above mentioned sampling techniques. The different sampling techniques were compared using different ML algorithms such as Support Vector Machine (SVM), Artificial Neural Networks (ANN), Decision Tree (DT) using PART algorithms and Logistic Regression (LR). Model performance was evaluated using G-mean, F-statistics and Area Under the receiver operating characteristic Curve (AUC). Other performance measures such as overall accuracy, weighted accuracy, Negative Predictive Value (NPV) and precision were also calculated. In this study 1,042 of patients with acute leukemias and chronic myeloid leukemia underwent allogeneic transplantation between 1997 and 2013 were analyzed. Baseline characteristics such as age groups (<20, 20-40 and >40), donor-sex-mismatch, disease stage (early, intermediate and advance), graft type (BM vs. PB), diagnosis (ALL, AML and CML) were used in building the predictive model. HLA mismatch and type of conditioning were not included because more than 95% of the patients were HLA-identical and received myeloablative conditioning. Analysis was performed using R studio. Results: Sampling techniques have significantly improved the model ability of predicting the Day-100 TRM using all the studying machine learning algorithms. As expected, DT showed less sensitivity to the imbalance class distribution as compared to other ML algorithms. However, this is justifiable because DT is created using a splitting criterion that maximizes the information gain (entropy)/Gini index which forces both classes to be addressed. LR showed inferior sensitivity compared to other ML algorithms. RUS/TLink showed the best performance using SVM, ANN and LR. On the other hand, RUS and ROS showed a comparable results using PART DT algorithm, [Figure 1].



A-050: The outcome of pediatric allogeneic stem cell transplantation at King Abdullah Specialized Children's Hospital

Muath Abuhaimed, Batal Aldosari, Bassam Alduwaifiry, Turki A. Alqahtani, Mohammed Essa 1 , Abdulrahman Alsultan 1

College of Medicine, King Saud bin Abdulaziz University for Health Sciences, 1 Department of Pediatric Hematology/Oncology, King Abdullah Specialized Children's Hospital, Riyadh, Saudi Arabia

Introduction: Allogeneic stem cell transplantation (SCT) is an important modality of therapy for children with cancer and inherited disorders such as thalassemia. In this study, we reviewed the allogeneic SCT experience of the Pediatric SCT program at King Abdullah Specialized Children's Hospital in Riyadh from January 2010-December 2014. Methods: The following data were collected through chart reviews including patients' demographics (age and gender), diagnosis, degree of HLA matching, stem cell source, conditioning regimens, and treatment outcomes. A total of 51 patients were transplanted during this period, of those 27 were males and 24 females. Results: The median age at transplantation was 5.1 (range, 0.2-13.4) years. A total of 45 patients were transplanted using matched related donors and 6 were transplant from unrelated cord blood transplant (UCBT). All patients engrafted successfully except 2 patients who had UCBT. The median time for neutrophils engraftment was 24 days (range, 9-58 days) and for platelets engraftment 25 days (range, 8-73). Transplant related mortality at day 100 was 5%. The frequency of acute GVHD grade (II-IV) was 7.8% and for grade (III-IV) was 2%. There was only 9% with chronic GVHD. The 1-year and 2-year event free survival was 83.7%. In addition, the 1-year overall survival was 89.4% and the 2-year overall survival was 86.7%. The events were two graft failure with the cord transplants and two late graft failure in match related (bone marrow), three of those underwent successful second transplant. The causes of death were pulmonary toxicity in 2 patients, sever GVHD in 1 patient and leukemia relapses in 2 patients. Conclusion: We conclude that the survival outcome of pediatric allogeneic SCT at KASCH is comparable to those reported from other centers. We observed low rate of GVHD in our study, which is expected given that majority of cases were transplanted from matched related donors.

A-051: Outcome of pediatric autologous hematopoietic stem cells transplantation at KAMC-Riyadh

R. Hawsawi 1 , M. Al-Harbi 1 , H. Khormi 1 , D. Jawdat 1,2 , Al-Sultan A 3

1 College of Medicine King, Saud bin Abdulaziz University for Health Sciences, 2 King Abdullah International Medical Research Center, 3 Pediatric Hematology/Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia

Background: Autologous stem cell transplantation (ASCT) is an effective treatment in patient with high-risk tumors. ASCT have been used for decades because stem cells offer the possibility of a renewable source for replacement cells and tissues to treat. However, only limited data have been published about the outcomes from Saudi Arabia. Therefore, this study was conducted to analyze new experience in KAMC. Objective: This study is designed to identify the outcomes of ASCT in KAMC-Riyadh. Methods: In this study we used a retrospective cohort study in KAMC in Riyadh. It supplemented by chart review of all children under the age of 14 years who were admitted to oncology center from establishment of the program (2010) to January 2015 for ASCT. The data has reviewed to identify outcomes in the early post-transplant period within the first 100 days (+100). ASCT is done by collecting HSCs from the same patients. Stem cells that are used in transplants are frozen and stored in stem cell laboratory to be given back to the same patients. This procedure may be done once or many times. After collecting data, SPSS has been used for analyzing data. Results: A total of 47 ASCT were performed in 33 patients. The median age at ASCT was 2.9 years (range, 1.1-12.8 years). Twenty-five patients (75.8%) had undergone a single ASCT. Out of 47 transplants, 29 transplants for 15 patients with brain tumor (61.7%), 13 transplants for those who had neuroblastoma (27.7%), 2 patients had lymphoma (4.3%), 2 had relapse Wilms tumor and 1 had Ewing's sarcoma. All patients were identified as having advanced stages and all of them had successful engraftment of neutrophils and platelets. None of them had transplant-related mortality, but deaths were due to tumor progression or recurrence. The probability of OS at 1 and 5 years was 95% and 50%, respectively. Five-year EFS was 45%. Conclusion: Using ASCT in pediatrics with malignant diseases induces successful overall survival rate. High dose chemotherapy with ASCT was well tolerated with no significant complications. Available evidence indicates that treating with ASCT may improve survival rates. Despite these findings, further multi-institutional collaborative studies are recommended to get helpful information upon our population outcome.

A-052: Predicting the odds of day-100 treatment related mortality using supervised machine learning in acute and chronic myeloid leukemia patients underwent allogeneic stem cell transplantation: 1042 cases

Tusneem A. Elhassan, N. Chaudhri, Ghuzayel Aldawsari, Fahad Alsharif, Hazzaa Alzahrani, Said Yousuf Mohamed, Walid Rasheed, Amr Hanbali, Syed Osman Ahmed, Marwan Shaheen, Feras Alfraih, Fazal Hussain, Fahad Almohareb, Mahmoud Aljurf

Oncology Center, King Faisal Specialist Hospital and Reseach Center, Riyadh, Saudi Arabia

Introduction: Transplant data are becoming more complex where sometimes conventional statistical modeling fails to hold. On the other hand, supervised machine learning (a field of Artificial Intelligence) provides state-of-the-art algorithms for model building by learning from data instances using both input and output measures. Generalized Boosting Model (GBM), Support Vector Machine (SVM) and Artificial Neural Networks (ANN) are some examples of these algorithms. GBM is an optimization on Decision Trees (DT) that uses boosting algorithms in order to combine the week DT classifiers into a single strong classifier in a stage-wise fashion. While SVM is a technique for constructing an optimal separating hyper plane between two classes in cases where classes are not linearly separable. On the other hand, ANN is a type of learner that extracts the linear combinations of the input features and models the target as a non-linear function of these features. Materials (or Patients) and Methods: Supervised machine learning predictive models such as GBM, SVM and ANN were compared to Logistic Regression (LR) in predicting day-100 Treatment Related Mortality (TRM). Models were trained using 70% of the dataset while 30% of the data was kept for the validation purpose. Predictive ability of the model was assessed using Area Under the receiver operating characteristic curve (AUC). AUC was obtained to measure the in-sample fit and out-sample fit using training and validating data set respectively. Five-fold cross validation was used to avoid model over fitting and ensure model stability. Decision matrix was used in order to adjust for TRM non-proportionality using prior probabilities and appropriate decision consequences. Average profit summary statistics was computed to assess model performance. In this study 1,042 of patients with Acute and Chronic Myeloid Leukemia underwent Allogeneic transplantation between 1997 and 2013 were analyzed. Baseline characteristics such as age groups (<20, 20-40 and >40), donor-sex-mismatch, disease stage (early, intermediate and advance), graft type (BM vs. PB) were used in building the predictive model. However, HLA mismatch and type of condition were not included because more than 95% of the patients were HLA-identical and received myeloablative conditioning. Analysis was performed using SAS Miner 13.1 . Results: Machine learning based model achieved an AUC of 70%, 69% and 61% using GBM, ANN and SVM respectively compared to 67% for LR in training data. While, for validation data, the AUC was 65%, 61% and 60% for SVM, GBM and ANN respectively compared to 62% for LR. However, all models achieved an accuracy of 85% in training and validation data sets, [Table 1]. Conclusion: Machine learning based models showed a comparable performance results compared to LR. However, GBM showed an improved performance that could be promoted by identifying more predictive risk factors that might contribute to the prediction of day-100 TRM. Hence, improving the model deterministic ability.



A-053: Autologous hematopoietic cell transplantation in a patient with relapsing-remitting multiple sclerosis following a short period of fingolimod washout

Mohamed Ali, Panayotis Kaloyannidis, Hani Al-Hashmi, Reem Bunyan

King Fahad Specialist Hospital, Dammam, Dammam, Saudi Arabia

Multiple sclerosis (MS) is a demyelinating, inflammatory disease of the central nervous system (CNS). It's a chronic and devastating autoimmune disease. Current management guidelines for relapsing forms of MS include monoclonal antibodies (e.g. natalizumab, alemtuzumab, rituximnab and daclizumab) and oral agents (e.g. fingolimod and cladribine) to target molecules or cells which are important in the immunopathogenesis of multiple sclerosis. These agents seem to have a considerable effect on relapsing-remitting multiple sclerosis (RRMS), but may also be associated with serious side effects, suboptimal response or breakthrough disease. The immunosuppression provided by high-dose chemotherapy with stem cells rescue has been studied only in small cohorts. The safety challenges associated with stem cells transplantation in MS patients are disease reactivation and rebound during the long washout period post discontinuation of immunomodulating drugs, in addition to disease flares during stem cell mobilization and the lymphocyte depletion incorporated into stem cell rescue procedures. There are also concerns of high-dose therapy toxicities unique to MS patients. We hereby report a case of 48 years old male with a diagnosis of RRMS for 14 years. He experienced neurological disability worsening on several treatments including natalizumab and fingolimod. He underwent autologus stem cells transplantation (ASCT). Fingolimod was discontinued three weeks prior to mobilization. Peripheral haematopoietic stem cells were mobilized with cyclophosphamide 2 g/m 2 and filgrastim 10 μg/kg/day. The conditioning regimen was BEAM/ATG protocol (BCNU 300 mg/m 2 ; etoposide 800 mg/m 2 ; cytosine-arabinoside 800 mg/m 2 ; melphalan 140 mg/m 2 ; ATG 7.5 mg/kg). The patient tolerated the procedure well and had full engraftment by day 18. The early transplant course was associated with febrile urinary tract infection, CMV and EBV reactivations. These infectious complications were successfully managed with the use of antibiotics, valganciclovir and rituximab respectively. To date, and for more than nine months, the patient remains out of any immunosuppressive treatment with no clinical or radiological evidence of the disease. We conclude that the quality of stem cells collection; efficacy and tolerability of high dose chemotherapy and time to engraftment were not affected by fingolimod prior treatment and the short washout period. To our knowledge this is the first case of ASCT for MS in Middle East.

A-054: Efficacy and safety of VCEP-M for induction treatment of mixed phenotypic acute leukemia

Ahmad Alhuraiji, Ahmed Shad, Tarek Owaidah, Fahad Almohareb, Fahad Alsharif, Said Mohamed, Ghuzayl Aldawsri, Mohammad Islam, S. O. Ahmed, Amr Hanbali, Mahmoud Aljurf, Walid Rasheed King Faisal

Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Background: Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia, characterized by an aggressive behavior & a tendency towards resistance to therapy and overall poor outcome. The aim of the study is to evaluate the efficacy and toxicity of VCEP-M protocol. Methods: This was a retrospective study. We included patients diagnosed with mixed phenotypic acute leukemia at King Faisal Specialist Hospital and research Centre (based on WHO and EGIL criteria) from 2002 to 2014 treated with upfront VCEP-M Protocol. We excluded patients who are less than 15 years of age and patients treated outside our institution. Data were collected from our electronic tumor registry. Results: We included 19 patients who met the inclusion criteria. Ten patients were salvaged at day 14 Bone marrow with Fludarabine 30 mg/m 2 /day and cytarabine 2 g/m 2 /day (D1-5) (FA) chemotherapy. Complete remission (CR) rate at day 28 bone marrow was 95% (18 patients). Thirteen patients proceeded to allogenic stem cell transplantation (SCT). All 6 patients who had not had SCT died. Overall survival (OS) and disease free survival (DFS) at 5 years were 54% and 57% respectively. Treatment related toxicity were mainly sepsis (11 patients) and disseminated intravascular coagulation (DIC) (2 patients). There was no reported treatment related deaths Conclusions: VCEP-M appears effective in the treatment of MPAL with a safe toxicity profile. All patients would likely benefit from SCT. Larger studies are required to validate these results.




 

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