|Year : 2014 | Volume
| Issue : 4 | Page : 156-160
Successful outcome of postsplenectomy chemotherapy in an acute myeloid leukemia patient with massive bilharzial splenomegaly
Shahid Iqbal1, Syed Zaidi1, Khalid Al-Mohaimeed2, Imran Tailor1, Ibraheem Almotabi1, Nawal Al-Shehry1, Assem El-Ghazaly1, Samer Al-mudaibegh1, Mamoun Ibrahim1, Karrar El-Hussein1, Abdulaziz Al-Humaidi1
1 Department of Adult Hematology and BMT, Comprehensive Cancer Center, King Fahd Medical City, Riyadh, Saudi Arabia
2 Department of Surgery, King Fahd Medical City, Riyadh, Saudi Arabia
|Date of Web Publication||13-Dec-2014|
Dr. Shahid Iqbal
Department of Adult Hematology and BMT, Comprehensive Cancer Center, King Fahd Medical City, Riyadh
Source of Support: None, Conflict of Interest: None
Bilharzial hepatic fibrosis is usually accompanied by marked enlargement of the spleen. Schistosoma hematobium and Schistosoma mansoni infestation is endemic in Africa and southern part of Saudi Arabia. Patients with acute myeloid leukemia (AML) present with clinical features resulting from bone marrow failure, symptoms resulting from organ infiltration with leukemic cells (including splenomegaly), or both. Co-occurrence of bilharzial splenomegaly and AML is intuitively possible. Spontaneous splenic rupture has been reported to be catastrophic in both conditions and rarely splenic rupture may be the first manifestation of AML. Splenectomy is a considerable option in symptomatic splenomegaly in schistosomiasis. An enlarged spleen may also serve as a sanctuary site for residual leukemic cells after chemotherapy. Splenectomy has been reported in pediatric AML after chemotherapy and selected adult patients with myelodysplastic syndrome and myeloproliferative neoplasm (MPN). However, to the best of our knowledge, this is the first report of successful outcome of splenectomy prior to induction chemotherapy in an AML patient who presented with huge symptomatic splenomegaly due to past history of schistosomiasis, had also shown refractoriness to platelet transfusion due to hypersplenism and vaginal bleeding. Splenectomy in such a scenario was a difficult decision but was feasible with adequate expertise, vigilance and blood products availability. The patient is alive in complete remission with good performance status more than 2½ years after therapy.
Keywords: myeloid leukemia, bilharziasis, splenectomy, splenomegaly
|How to cite this article:|
Iqbal S, Zaidi S, Al-Mohaimeed K, Tailor I, Almotabi I, Al-Shehry N, El-Ghazaly A, Al-mudaibegh S, Ibrahim M, El-Hussein K, Al-Humaidi A. Successful outcome of postsplenectomy chemotherapy in an acute myeloid leukemia patient with massive bilharzial splenomegaly. J Appl Hematol 2014;5:156-60
|How to cite this URL:|
Iqbal S, Zaidi S, Al-Mohaimeed K, Tailor I, Almotabi I, Al-Shehry N, El-Ghazaly A, Al-mudaibegh S, Ibrahim M, El-Hussein K, Al-Humaidi A. Successful outcome of postsplenectomy chemotherapy in an acute myeloid leukemia patient with massive bilharzial splenomegaly. J Appl Hematol [serial online] 2014 [cited 2020 Feb 21];5:156-60. Available from: http://www.jahjournal.org/text.asp?2014/5/4/156/146951
| Introduction|| |
Spleen is a hematopoietic organ that normally carry 30-50% of the body's circulating granulocytes and up to 40% of platelets.  Many disease processes may predispose patients to splenomegaly including schistosomiasis and hematological malignancies. Bilharziasis results from chronic schistosomal infestation and is endemic in Africa and Jazan and Aseer regions of Saudi Arabia.  Schistosomal eggs generate an intense immune response leading to granulomatous reaction and fibrosis in the hepatobiliary system, splanchnic circulation, and urinary bladder.  It is usually accompanied by massive enlargement of the spleen with hypersplenic activity, leukopenia, thrombocytopenia, and hypochromic anemia. , Patients with acute myeloid leukemia (AML) present with clinical features resulting from bone marrow failure and organ infiltration with leukemic cells (including splenomegaly), or both. Development of coagulation abnormalities and leukostasis may also be seen.  Rarely, both diseases may occur together. Spontaneous splenic rupture has been reported to be catastrophic in both conditions and spontaneous rupture may be the first manifestation of AML. ,, Splenectomy is a considerable option in symptomatic splenomegaly in schistosomiasis. An enlarged spleen may also serve as a sanctuary site for residual leukemic cells after chemotherapy. Hence, splenectomy has also been reported after chemotherapy in pediatric AML patients and also in selected adult patients with myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN). ,,,,,, However, to the best of our knowledge, a successful outcome of splenectomy prior to AML induction chemotherapy has not been reported in English literature.
Here, we present the first case report of successful outcome of splenectomy followed by induction and consolidation chemotherapy in an AML patient who presented with huge symptomatic splenomegaly due to past history of treated schistosomiasis, had related chronic liver disease and also had platelet transfusion refractoriness due to hypersplenism.
| Case Report|| |
A 48-year-old lady presented to our institution from the southern part of Saudi Arabia with history of bilharziasis. She was adequately treated with praziquantel 7 years back. She had chronic liver disease secondary to schistosomiasis with portal hypertension, grade II esophageal varices, portal vein thrombosis, moderate ascites and symptomatic massive splenomegaly that had lately become more painful. Her Child-Pugh grade was C. She also had a history of central retinal vein thrombosis related decreased vision in left eye. She had presented at local hospital with increasing fatigability and exertional dyspnea and heavy vaginal bleeding. She was found to have white blood count (WBC) count of 11.30 × 10 ^ 9/L, hemoglobin of 8.1 g/dL and platelet count of 9 × 10 ^ 9/L. Coagulation profile revealed PT of 16.4 s, INR 1.4, APTT 39.9 s, Fibrinogen 2.9 g/dL, D-dimers 3.6 mg/L. Biochemistry at initial presentation was remarkable for lactate dehydrogenase 885 U/L, uric acid 177 μmol/L, bilirubin total 2.8 mg/dL, bilirubin direct 0.7 mg/dL, aspartate aminotransferase 51 U/L, alanine aminotransferase 66 U/L, Alkaline phosphates 283 U/L, albumin 32 g/L. Serology was negative for hepatitis B virus, Hepatitis C virus, hepatitis A virus, HIV, and human T-lymphotropic virus-1 and 2. Schistosomal serology indirect hemagglutination was positive with antibody titer of 1:64. She was supported with packed red blood cells (PRBCs) and platelet transfusions. Her blood film examination [Figure 1] revealed 43% blasts and bone marrow biopsy [Figure 2], [Figure 3] and [Figure 4] showed hypercellular marrow studded with myeloblasts. Flowcytometery revealed 30% cells expressing CD45 (dim), CD13, CD33, CD11c, and MPO, and lacking expression of CD34 and HLADR. She was shifted to our institution for further management. She was pale and had abdominal distension with massive splenomegaly approximately 18 cm below left costal margin. After further work-up, she was considered intermediate-risk AML with normal karyotype (46, XX). Her abdominal computed tomography scan showed massive splenomegaly (30 cm) and cavernous transformation of the portal vein due to chronic portal vein thrombosis [Figure 5] and [Figure 6]. She had persistent per vaginal bleeding with low platelet count in spite of repeated platelet transfusions most likely due to consumption and secondary to hypersplenism. We had extensive discussion with the team of hematologists in our center and across the country related to therapeutic options. She agreed to take chemotherapy only after splenectomy as she believed this huge spleen will rupture during the chemotherapy. Eventually, it was agreed to offer her option of splenectomy before proceeding to induction therapy for AML if she consents for high-risk surgery. After explanation of risks benefits and alternatives, an informed consent for high-risk surgery was obtained. She was given standard pre-splenectomy vaccinations, and adequate blood products were arranged prior to surgery. Splenectomy was accomplished on October 10, 2011 through laparotomy along with an intercostal drain placement for the left sided pleural effusion and blood products support including platelets concentrate drip during the procedure. During perioperative and 24 h postoperative period, she received a total of 20 PRBCs, 22 platelet transfusions and 25 units of fresh frozen plasma. Coagulopathy dampened down over 24 h after splenectomy and blood products requirement decreased as she required four units of PRBCs and six platelet transfusions over the next 14 days prior to induction chemotherapy. Splenectomy was complicated by intra-abdominal abscess formation. She was managed successfully with broad spectrum antibiotics and ultrasound guided percutaneous drainage of the abscess. As expected, post-splenectomy blood picture in our patient did show neutrophilia (37.3 × 10 ^ 9/L), monocytosis, basophilia, increased platelet count (up to 62 × 10 ^ 9/L), increased nucleated RBCs (220/100 WBC), occasional Howell-Jolly bodies More Details and WBC reaching up to 37.3 × 10 ^ 9/L with blasts count up to 50% prior to chemotherapy.
|Figure 1: Microphotograph of peripheral blood film stained with Field's stain on ×1000 showing leukoerythroblastic picture with multiple large immature cells with high N:C ratio and open chromatin with prominent nucleoli in keeping with myeloblasts in acute myeloid leukemia|
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|Figure 2: Microphotograph of bone marrow aspirate stained with Field's stain on ×1000 showing multiple large immature cells with high N:C ratio and open chromatin with prominent nucleoli in keeping with myeloblasts in acute myeloid leukemia|
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|Figure 3: Bone marrow trephine biopsy section stained with (H and E) at ×100 showing extremely hypercellular marrow with no fat spaces|
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|Figure 4: Bone marrow trephine biopsy section stained with (H and E) at ×400 showing extremely hypercellular marrow with no fat spaces and studded with immature large cells (myeloblasts)|
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|Figure 5: Axial postcontrast computed tomography scan section showing massive splenomegaly and cavernous transformation of the portal vein due to chronic portal vein thrombosis|
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|Figure 6: Sagittal postcontrast computed tomography scan section showing massive splenomegaly up to 30 cm|
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Starting on October 26, 2011, she received AML induction chemotherapy with idarubicin 12 mg/m 2 /day for 3 days and cytarabine (Ara-C) 100 mg/m 2 /day continuous infusion for 7 days (3 + 7 protocol). Patient tolerated the induction chemotherapy fairly well and achieved complete remission. Postinduction chemotherapy she received a total of 10 units of PRBCs and 11 platelet transfusions until she recovered her counts and was discharged in a good condition. Induction was followed by three cycles of intermediate dose Ara-C (cytarabine), 1 g/m 2 BID on day 1, 3, and 5 due to her above-mentioned comorbidities. The last cycle was completed on February 22, 2012. She tolerated consolidation chemotherapy well except a lower urinary tract infection with extended spectrum beta-lactamase Escherichia More Details coli. Her chronic liver disease remained stable, and her portal vein showed cavernous transformation on follow-up imaging studies. She remains in complete remission and is doing fine with an Eastern Cooperative Oncology Group performance status of zero as confirmed on her last contact on July 22, 2014. She is maintained on oral penicillin V prophylaxis.
| Discussion|| |
In AML, massive splenomegaly is uncommon and usually is not a concern as chemotherapy is expected to take care of leukemic component in enlarged spleen. Splenectomy is a considerable option in schistosomiasis in the symptomatic patient with massive splenomegaly; but this procedure is associated with significant morbidity.  Rupture of the spleen is relatively common following significant blunt abdominal injury. Less commonly, cases of atraumatic rupture (also known as pathological splenic rupture) of normal or diseased spleens are also widely reported in the literature. ,,,,,, Spontaneous splenic rupture is a well-known, but life-threatening complication of leukemia. ,,,, Approximately, 18 cases of splenic rupture associated with AML have been reported in English literature.  Spontaneous splenic rupture as the first manifestation of AML has also been described. ,, An enlarged spleen may also serve as a sanctuary site for residual leukemic cells after chemotherapy. Hence, splenectomy has also been reported after chemotherapy in pediatric AML patients and also in selected adult patients with MDS or MPN. ,,,,,
Moreover, splenectomy seems a considerable therapeutic option in symptomatic massive splenomegaly when the cytopenia is severe, other causes of cytopenia like disseminated intravascular coagulation (DIC) have been ruled out, a reasonable survival time after splenectomy is expected, patient's general medical condition is satisfactory, and if surgeons experienced in performing splenectomy under adverse conditions are available.  Our patient developed AML on top of schistosomiasis related splenomegaly and had thrombocytopenic bleeding with refractoriness to platelet transfusions. Plausible factors responsible for splenomegaly in our patient included history of schistosomiasis, development of AML, and congestion due to portal hypertension and portal vein thrombosis. The splenectomy was performed by an experienced surgeon after an explicitly informed consent for this high-risk procedure in view of concurrent AML.
Short- and long-term splenectomy hazards have been well-studied in healthy veterans and those suffering from myeloid disorders. ,,,, Splenectomized cancer-free American veterans had an increased risk of pneumonia, meningitis, and septicemia, venous thromboembolism, certain solid tumors and hematologic malignancies: Non Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and any leukemia.  These results underscore the importance of vaccination, surveillance, and thromboprophylaxis after splenectomy.
Santos, et al. from MD Anderson Cancer Center, reported on splenectomy efficacy in alleviating symptoms and cytopenias, complications and impact on survival in patients with MPN.  Leukocytosis (76%) and thrombocytosis (43%) were associated with thromboembolic phenomena in 16% of patients. Postoperative mortality was 5%. 
To reduce the risks associated with splenectomy various strategies are recommended. Immunizations against encapsulated organisms (Streptococcus, meningcoccus, and Hemophilus influenza B) should be administered prior to surgery or at least prior to hospital discharge. Clinicians should also be aware of the reports that splenectomy in MPN patients was associated with acute bleeding (15%) and venous thrombosis (12%)  and increased in-hospital mortality from these complications. ,,, Perioperative thrombohemorrhagic complications decreased in the last decade through the use of monitoring and the prompt use of cytoreductive agents to counteract postsplenectomy thrombocytosis.  In AML patients, hemorrhagic complications are more likely due to failure of production of platelets and possibility of DIC due to neutropenic sepsis.
Splenectomy after chemotherapy has been studied in pediatric AML patients and also in selected adult MDS patients. ,,,,, In 1974 Fleming et al. explored the therapeutic and diagnostic value of splenectomy for children with AML in remission.  Of 29 consecutive untreated patients entering the study, fourteen patients underwent splenectomy when clinically in complete remission. Splenectomy was tolerated well. Histologic leukemia was found in 12 (85.7%) patients, most often in the spleen.  Steensma and Tefferi commented that splenectomy may be an effective but underutilized treatment option for distinct forms of MDS (e.g. hypoplastic MDS with bone marrow blast count <10%, refractory to initial immunosuppressive treatment and other drug therapies or refractory to transfusions). 
Our patient represents the first case report of a successful outcome in a unique setting as our patient developed AML after a longstanding history of treated schistosomiasis related massive splenomegaly and had thrombocytopenic bleeding with refractoriness to platelet transfusions. With good precautions, she successfully underwent splenectomy and then was able to receive induction chemotherapy and tailored consolidation chemotherapy for AML. She remains in complete remission and is enjoying good performance status more than 2½ years after this procedure. Although a difficult ordeal, but splenectomy in such a complex scenario is feasible provided adequate expertise and blood products support are available, and vigilance is exercised.
| References|| |
Wilkins BS. The spleen. Br J Haematol 2002;117:265-74.
al-Madani AA. Problems in the control of schistosomiasis in Asir Province, Saudi Arabia. J Community Health 1991;16:143-9.
Coutinho HM, Acosta LP, Wu HW, McGarvey ST, Su L, Langdon GC, et al.
Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum
infection. J Infect Dis 2007;195:288-95.
Farid Z, Prasad AS, Schulert AR, Sanstead HH, Elrooby AS. Bilharzial splenomegaly. Arch Intern Med 1964;113:37-41.
Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, et al.
Diagnosis and management of acute myeloid leukemia in adults: Recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453-74.
Singhal V, Kuiper J, Chavda K, Kashmer D. Spontaneous splenic rupture as first manifestation of acute myeloid leukemia: Case report and review of literature. J Clin Oncol 2011;29:e576-8.
Tan A, Ziari M, Salman H, Ortega W, Cortese C. Spontaneous rupture of the spleen in the presentation of acute myeloid leukemia. J Clin Oncol 2007;25:5519-20.
Han JS, Oh SY, Kim SH, Kwon HC, Hong SH, Han JY, et al.
A case of pathologic splenic rupture as the initial manifestation of acute myeloid leukemia M2. Yonsei Med J 2010;51:138-40.
Fleming I, Simone J, Jackson R, Johnson W, Walters T, Mason C. Proceedings: Splenectomy and chemotherapy in acute myelocytic leukemia of childhood. Cancer 1974;33:427-34.
Steensma DP, Tefferi A. The myelodysplastic syndrome (s): A perspective and review highlighting current controversies. Leuk Res 2003;27:95-120.
Kokhno AV, Mikhailova EA, Parovichnikova EN, Karen IN, Suren RK, Kaplanskaya IB, et al
. Splenectomy in patients with MDS. Blood 2010;116:1879.
Mesa RA, Nagorney DS, Schwager S, Allred J, Tefferi A. Palliative goals, patient selection, and perioperative platelet management: Outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic. Cancer 2006;107:361-70.
Tefferi A, Mesa RA, Nagorney DM, Schroeder G, Silverstein MN. Splenectomy in myelofibrosis with myeloid metaplasia: A single-institution experience with 223 patients. Blood 2000;95:2226-33.
Akpek G, McAneny D, Weintraub L. Risks and benefits of splenectomy in myelofibrosis with myeloid metaplasia: A retrospective analysis of 26 cases. J Surg Oncol 2001;77:42-8.
Aubrey-Bassler FK, Sowers N 613 cases of splenic rupture without risk factors or previously diagnosed disease: A systematic review. BMC Emerg Med 2012;12:11.
Renzulli P, Hostettler A, Schoepfer AM, Gloor B, Candinas D. Systematic review of atraumatic splenic rupture. Br J Surg 2009;96:1114-21.
Tartaglia AP, Scharfman WB, Propp S. Splenic rupture in leukemia. N Engl J Med 1962;267:31-3.
Hynes HE, Silverstein MN, Fawcett KJ. Spontaneous rupture of the spleen in acute leukemia. Report of 2 cases. Cancer 1964;17:1356-60.
Kristinsson SY, Gridley G, Hoover RN, Check D, Landgren O. Long-term risks after splenectomy among 8,149 cancer-free American veterans: A cohort study with up to 27 years follow-up. Haematologica 2014;99:392-8.
Santos FP, Tam CS, Kantarjian H, Cortes J, Thomas D, Pollock R, et al.
Splenectomy in patients with myeloproliferative neoplasms: Efficacy, complications and impact on survival and transformation. Leuk Lymphoma 2014;55:121-7.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]