|Year : 2016 | Volume
| Issue : 3 | Page : 102-107
Clinicopathological profile and utility of prognostic tools in peripheral T-cell lymphoma
D. Lokanatha, Namratha M.S. Udupa, Govind K Babu, KC Lakshmaiah, Linu A Jacob, Suresh M.C. Babu, KN Lokesh, LK Rajeev, AH Rudresha
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
|Date of Web Publication||26-Oct-2016|
Namratha M.S. Udupa
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore 560029, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: With the availability of three prognostic scores in Peripheral T-Cell Lymphoma (PTCL)-International Prognostic Index (IPI), International Peripheral T-Cell Lymphoma Project (IPTCLP), and Prognostic Index for PTCL-Unspecified (PIT), we intended to find out usefulness of each of them in prognostication of patients. Objectives were to know the clinicopathological profile and to analyze the effectiveness of these prognostic scores and their individual parameters in predicting Complete Remission (CR) rates, Progression Free Survival (PFS), and Overall Survival (OS) in PTCL.
Materials and Methods: All 55 patients were treated as per institute chemotherapeutic protocols. Response assessment was done by Cheson’s criteria. At baseline, patients were risk stratified with the three scores into low, low- and high-intermediate, and high-risk groups. Outcomes − CR and survival − PFS and OS were analyzed and compared in the risk groups as stratified by the three prognostic scores. Clinical and pathological details were also analyzed.
Results: For PFS estimation, IPI and IPTCLP scores proved be the best prognostic tools. For OS, IPTCLP score emerged to be the single best prognostic tool. CR correlated with Ann Arbor stage of disease and IPI score.
Conclusion: PTCL NOS (Not Otherwise Specified) was the most common histological subtype. IPI score correlated the best with CR reflecting as PFS, but was not related statistically with OS in the local population. IPTCLP score has consistent correlation with prognosis more so with OS than PFS, but no relationship with CR rate.
Keywords: Clinicopathological profile, peripheral t-cell lymphoma, prognostic tools
|How to cite this article:|
Lokanatha D, Udupa NM, Babu GK, Lakshmaiah K C, Jacob LA, Babu SM, Lokesh K N, Rajeev L K, Rudresha A H. Clinicopathological profile and utility of prognostic tools in peripheral T-cell lymphoma. J Appl Hematol 2016;7:102-7
|How to cite this URL:|
Lokanatha D, Udupa NM, Babu GK, Lakshmaiah K C, Jacob LA, Babu SM, Lokesh K N, Rajeev L K, Rudresha A H. Clinicopathological profile and utility of prognostic tools in peripheral T-cell lymphoma. J Appl Hematol [serial online] 2016 [cited 2020 Apr 9];7:102-7. Available from: http://www.jahjournal.org/text.asp?2016/7/3/102/192987
| Introduction|| |
Peripheral T-Cell Lymphoma (PTCL) is a group of aggressive lymphoid neoplasms with varied incidences worldwide. It is group of heterogeneous diseases and is also scarce. In Western countries, it has an incidence of about 5–10% of all non-Hodgkin’s lymphomas (NHL),,, whereas in the Eastern countries it has a higher incidence.,
The median survival of PTCL is about 2–3 years. In view of its poor prognosis among NHLs, the need for individual and more accurate prognostic tools was appreciated. The International Prognostic Index (IPI) was initially tailored from a study on aggressive lymphomas including PTCL and its usefulness in T-Cell Lymphomas has been upheld by results from another study. A prognostic model for PTCL-Unspecified (PTCL-U) called PIT (Prognostic Index for PTCL-U) was found to have a superior predictive capacity as compared to IPI in a study by Gallamini et al. It was formulated by the ‘Intergruppo Italiano Linfomi’ for patients with PTCL NOS (Not Otherwise Specified). The latest score was the International Peripheral T-Cell Lymphoma Project (IPTCLP), which was concluded in a study to be the best one correlating with the Overall Survival (OS), compared to IPI which relates better with Complete Remission (CR) rates. As on today, IPI score is being used most commonly to prognosticate all NHLs.
With the availability of these three scores, we intended to find out the usefulness of each one of them in prognostication of patients with PTCL.
| Materials and Methods|| |
The study was conducted at the Department of Medical Oncology in Kidwai Memorial Institute of Oncology, a referral centre for oncology at Bangalore in South India. It was by a systematic review of case files of the 55 patients diagnosed to have PTCL and treated at the institute from January 2005 to December 2011. Histopathology review by hematopathologists was done.
The details noted down were the demographic profile of the patient, clinical presentation, extra nodal sites of involvement, histological subtype of PTCL, chemoregimen used, interim and final response assessment and follow-up details including Progression Free Survival (PFS) and OS. All the patients were prognosticated by three different approved scores − IPI, PIT, and IPTCLP at the start of treatment. IPI score considers age, eastern cooperative oncology group (ECOG) Performance Status (PS), serum lactate dehydrogenase (LDH), number of extra nodal sites, and Ann Arbor stage of disease. PIT score was based on age, PS, serum LDH levels, and bone marrow (BM) involvement. IPTCLP score takes into consideration age, PS, and platelet count as main variables. The IPI score 0–1 was defined as low-risk, 2 was low-intermediate risk, 3 was high-intermediate risk, and 4–5 was high-risk. The PIT score was classified into four risk groups as low-risk (PIT score 0), low-intermediate risk (PIT score 1), high-intermediate risk (PIT score 2), and high-risk (PIT score 3–4). The IPTCLP score 0 was defined as low-risk, 1 was low-intermediate risk, 2 was high-intermediate risk, and 3 was high-risk.
Treatment and follow-up
All the patients were treated as per institute chemotherapeutic protocols. Most of the patients who were fit for treatment received cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone (CHOP) (n = 47, 85.4%), a few of patients received etoposide with CHOP (n = 5, 9%) and the rest received best supportive care only (n = 3, 5.4%).
Follow-up details were noted down for a minimum period of 3 years or till disease progression or till death, whichever is earlier.
It was done by Cheson’s criteria., Responses were categorized as Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).
Objective of study
To know the clinicopathological profile and to analyze the effectiveness of these prognostic scores and their individual parameters in predicting CR rates, PFS, and OS in a patient of PTCL.
All patients above 15 years of age diagnosed of PTCL and treated at the institute.
All patients partially treated outside presenting as relapse/PD, primary cutaneous T-Cell Lymphoma, and T lymphoblastic lymphoma.
The statistical analysis was performed using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version 22.0 for Windows). Statistical analyses of prognostic impact of these three scores on PFS and OS were done with Kaplan Meier and Log rank test survival analysis. Association of the individual parameters (age, PS, LDH, stage, extra nodal involvement, BM involvement, and platelet count) with survival and Complete Response (CR) rates were done by univariate analysis. Categorical data were compared with Fisher exact test.
| Results|| |
Among the 55 patients studied, males were more common − 43 (78.18%) compared to females − 12 (21.81%). Mean age of the patient population was 53.29 years (18–86 years). Most of patients had ECOG PS of 1 (50%) followed by 3 (25%), 2 (17.3%), 4 (5.8%), and 0 (1.9%). Mean LDH was 559.25 U/L (225–1156). Extra nodal involvement was seen in 38 (69%) patients. Most commonly involved sites were lung in 12 (31.5%), liver in 12 (31.5%), spleen in 11 (28.9%), nasal cavity and nasopharynx in 7 (18.4%) patients. The Ann Arbor stage at presentation was stage I in 15 (27.27%), II in 10 (18.18%), III in 14 (25.45%), and IV in 16 (29.09%) of patients. The most common histological subtype was PTCL NOS seen in 45 (81.8%) followed by Anaplastic Large Cell Lymphoma (ALCL) in 6 (10.9%), Extra nodal NK/T-Cell Lymphoma (ENKTL) in 3 (5.45%), and Angioimmunoblastic T-Cell Lymphoma (AITL) in 1 (1.8%) of all patients. BM involvement was seen in only 7 (12.72%) patients. Skin involvement in the form of pruritus, papules, nodules, and plaques with secondary ulceration was seen in 11 (20%) patients [Table 1].
Treatment outcome in relation to individual parameters
Median PFS in the study population was 9.8 months and median OS was 13.8 months. CR rates postchemotherapy was 29%. Median PFS and OS in those aged more than 60 years were 8.8 and 13.2 months, respectively, whereas they were 10.2 and 13.9 months in those younger than 60 years of age. The difference was not statistically significant. Similarly, age groups were not statistically significant in the prediction of CR rates (29.9% vs 28.5% in the respective groups). PFS in stages I, II, III, and IV were 11, 14, 13, and 4 months, respectively, and OS was 11, 17, 16, and 7 months, respectively. Stage of disease was not significant statistically as an independent parameter in predicting survival of patients (P = 0.713 for PFS and P = 0.694 for OS). CR rates were significantly different in those with diseases in stages I and II (56%) as compared to those with stages III and IV (6.6%) diseases. Thus, stage of the disease was an important predictor as far as CR rates postchemotherapy were concerned (P = 0.042). ECOG PS, multiple extra nodal involvement and LDH as individual parameters were also not associated with PFS, OS nor CR rates. Median PFS in those with BM involvement was 4 months and in those without was 9 months and this was also not statistically significant as an independent parameter of PIT score (P = 0.804). Difference in OS of 4 months (7 and 11 months in those with and without BM involvement) was also not statistically significant (P = 0.753). CR rates were also not related to the involvement of BM by disease. Platelet count which was a variable in IPTCLP score did not show statistically significant association with the outcomes-PFS (P = 0.947), OS (P = 0.618) nor CR rates (P = 0.7).
Treatment outcome in relation to the three prognostic scores
Median PFS in low (0, 1), low-intermediate (2), high-intermediate (3), and high (4, 5) risk groups of IPI were 17, 14, 4, and 7 months, respectively. The PFS in relation to change of IPI scores was more significant in low-risk groups. As an entire cohort of patient population it was just approaching statistical significance (P = 0.059) [Figure 1]. Median OS in the four risk groups stratified by IPI score were 23, 17, 7, and 7 months, respectively. OS did not show a statistically significant association with IPI scores (P = 0.077) [Figure 1]. CR rates in the different risk groups were 42%, 33%, 17%, and 2%. This showed a statistically significant association with IPI score (P = 0.03).
Median PFS in low (0), low-intermediate (1), high-intermediate (2), and high (3, 4) risk groups of IPTCLP score were 15, 9, 3, and 7 months, respectively. This was just approaching statistical significance with P value being 0.056, more so in the low, low-intermediate, and high-intermediate risk groups. OS in the four groups were 17, 11, 6, and 10 months, respectively. OS showed a statistically more significant association with IPTCLP score, particularly in low and intermediate risk groups (P = 0.04) [Figure 2]. CR rates were not related statistically with the risk groups of IPTCLP score.
PIT score did not show a statistically significant association in any particular risk group of patients with P value being 0.157 for PFS and 0.8 for OS. The median PFS in low (0), low-intermediate (2), high-intermediate (3), and high (3, 4) risk groups of PIT score were 24, 15, 5, and 2 months, respectively. The respective OS in four risk groups were 28, 16, 8, and 6 months, respectively. It can be inferred that neither PIT score nor its unique composite variable- BM involvement at presentation did prove to be of prognostic utility for survival and/or CR rates in the patient population.
| Discussion|| |
Our population had a lower median age of occurrence of PTCL (53.29 years) compared to other studies on Eastern population (56–62 years),, whereas it was higher than the mean age of a study on Korean population (46.6 years). In most of the studies, it has been shown that the disease has a male preponderance akin to the results in our study (M:F − 3.58:1)., PS ≥ 2 was seen in 48.1% of our patients, which is comparable to the range (23–43%) in various other series. In the patient cohort, 54.5% had stages III and IV illnesses. This is lower as compared to the increased presence (67–83%) of higher stage diseases as mentioned in the same review series. Elevated LDH was seen in more (89%) patients than that (57–65%) in many other studies.,,
In our patient cohort, PTCL NOS (81.8%) was the most common histological subtype followed by ALCL (10.9%), ENKTL (5.45%), and AITL (1.8%). It can be noticed here that though PTCL NOS is the most common histology worldwide, it is more common in our patient population compared to many other studies (25.9–46%).,, The rarer histological types were more uncommon in our population. ENKTL, AITL, and ALCL were quite rare compared to another study in Taiwan which had a prevalence of 18.2%, 14.2%, and 13%, respectively.
BM involvement in the present series was in 12.72% of patients which is quite low as compared to that (25.8–39%) in many other patient populations.,,, In a review series, it has been shown that various types of PTCL have varying rates of BM involvement from 5 to 70%, highest in AITL (70%) followed by PTCL NOS (20–40%), AITL, and ENKTL (<5%). The fact that our patient population has higher prevalence of PTCL NOS subtype explains the lower occurrence of BM involvement.
Extra nodal involvement in our study (69%) was much higher than that (37%) in another study on Western population. Simultaneous extra nodal and nodal involvement were seen in 45.45% and isolated extra nodal involvement was present in 23.63% in our series as compared to respective involvements of 56% and 30% in a study. B symptoms in this series were present in 63.6% of patients compared to that (38–57%) in various studies.,,,, Most common sites of extra nodal involvement were lung/pleura and liver, each in 31.5% of population followed by spleen in 28.9%, skin in 20%, nasal cavity, and nasopharynx in 18.4% of patients. Lung and pleural involvement is clearly higher in our study compared to that (9.8–24%) in a few other studies.,,, Lung involvement was in the form of non-infectious consolidation, nodules, interstitial infiltrates, hilar lymphadenopathy, and pleural effusion. Liver involvement in the form of radiological hypodense lesions, biochemical abnormalities, and jaundice was present in 31.5% of patients. This is higher than that (12.9%) quoted in another study. Splenic involvement was at par with that (24.6%) in the same study. In a review series, the range of liver involvement quoted is 9–34%. Cutaneous involvement was seen in 20% of patients and this is comparable to the results (10–18%) obtained in other studies.,CR rates, PFS, and OS in the present study were 29%, 9.8 months, and 13.8 months, respectively. CR rate is comparable with that (30.6%) in another study with CHOP based chemotherapy. A few other studies have quoted a higher range of 38.7–57.4% in CR rates.,, Median PFS was 15 months in a study which is higher than that of our patients. Median OS in the same study was less than 2 years.
For PFS estimation, IPI and IPTCLP scores proved to be the best prognostic tools. For OS, IPTCLP score emerged to be the single best prognostic tool. CR rates correlated with Ann Arbor stage of the disease and IPI score. This is similar to the result obtained in another study. PIT score was unfortunately futile in the prediction of none of the rates of PFS, OS, and CR.
There were some limitations in our study. One of them was the retrospective study design. This was because of the rarity of the disease, which precluded a prospective design. Second, since the study was at a time when people neither opt for nor afford stem cell transplant, the outcomes of these prognostic scores on those after stem cell transplant were not possible. Third, since the number of patients in the rarer histological subtypes was less, no subset analysis was possible. There were some merits to this study as well. We strongly believe that the results from this study can be extrapolated to prognosticate those patients who do not go for stem cell transplant due to various reasons. This study is also one of the largest of its kind on Indian population, considering the rarity of its occurrence.
Ours was a retrospective study design and the relatively small number of patients in the special subtypes of PTCL limited the subset analyses of various outcomes of the study.
| Conclusion|| |
IPI score correlates the best with complete response rates to chemotherapy reflecting as PFS, but was not related statistically with OS in the local population. IPTCLP score has consistent correlation with prognosis more so with OS than PFS, but no relationship with CR rate. BM involvement both independently and also in its composite PIT score has no predictive value, reflecting on the questionable inclusion of BM involvement in the PIT score as applied on local population. By and large, the only individual parameter which proved to be of use in the prediction of CR was the Ann Arbor stage of the disease.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin’s lymphomas: Distributions of the major subtypes differ by geographic locations. Non-Hodgkin’s Lymphoma Classification Project. Ann Oncol 1998;9:717-20.
Vose J, Armitage J, Weisenburger D, International T-Cell Lymphoma Project. International Peripheral T-Cell and natural killer/T-Cell Lymphoma study: Pathology findings and clinical outcomes. J Clin Oncol 2008;26:4124-30.
Ascani S, Zinzani PL, Gherlinzoni F, Sabattini E, Briskomatis A, de Vivo A et al.
Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. Classification. Ann Oncol 1997;8:583-92.
Au WY, Ma SY, Chim CS, Choy C, Loong F, Lie AK et al.
Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization classification scheme: A single center experience of 10 years. Ann Oncol 2005;16:206-14.
Prochazka V, Faber E, Raida L, Papajik T, Vondrakova J, Rusinakova Z et al.
Long-term outcome of patients with peripheral T-cell lymphoma treated with first-line intensive chemotherapy followed by autologous stem cell transplantation. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2011;155:63-9.
A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med 1993;329:987-94.
Gisselbrecht C, Gaulard P, Lepage E, Coiffier B, Briere J, Haioun C et al.
Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Groupe d’Etudes des Lymphomes de l’Adulte (GELA). Blood 1998;92:76-82.
Gallamini A, Stelitano C, Calvi R, Bellei M, Mattei D, Vitolo U et al.
Peripheral T-cell lymphoma unspecified (PTCL-U): A new prognostic model from a retrospective multicentric clinical study. Blood 2004;103:2474-9.
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM et al.
Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999;17:1244.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ et al.
Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-86.
Lin HN, Liu CY, Pai JT, Chang FP, Yang CF, Yu YB et al.
How to predict the outcome in mature T and NK cell lymphoma by currently used prognostic models? Blood Cancer J 2012;2:e93.
Kim YR, Kim JS, Kim SJ, Jung HA, Kim SJ, Kim WS et al.
Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS) treated with anthracycline-containing chemotherapy. J Hematol Oncol 2011;4:34.
Yoon SO, Suh C, Lee DH, Chi HS, Park CJ, Jang SS et al.
Distribution of lymphoid neoplasms in the Republic of Korea: Analysis of 5318 cases according to the World Health Organization classification. Am J Hematol 2010;85:760-4.
Ameen R, Sajnani KP, Albassami A, Refaat S. Frequencies of non-Hodgkin’s lymphoma subtypes in Kuwait: Comparisons between different ethnic groups. Ann Hematol 2010;89:179-84.
Rodriguez-Abreu D, Filho VB, Zucca E. Peripheral T-cell lymphomas, unspecified (or not otherwise specified): A review. Hematol Oncol 2008;26:8-20.
Kojima H, Hasegawa Y, Suzukawa K, Mukai HY, Kaneko S, Kobayashi T et al.
Clinicopathological features and prognostic factors of Japanese patients with “peripheral T-cell lymphoma, unspecified” diagnosed according to the WHO classification. Leuk Res 2004;28:1287-92.
Prochazka V, Trneny M, Pytlik R, Vasova I, Kral Z, Belada D et al.
Peripheral T-cell lymphoma, unspecified − The analysis of the data from the Czech Lymphoma Study Group (CLSG) registry. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2007;151:103-7.
Rüdiger T, Weisenburger DD, Anderson JR, Armitage JO, Diebold J, MacLennan KA et al.
Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): Results from the Non-Hodgkin’s Lymphoma Classification Project. Ann Oncol 2002;13:140-9.
Montalbán C, Obeso G, Gallego A, Castrillo JM, Bellas C, Rivas C. Peripheral T-cell lymphoma: A clinicopathological study of 41 cases and evaluation of the prognostic significance of the updated Kiel classification. Histopathology 1993;22:303-10.
Gutiérrez-García G, García-Herrera A, Cardesa T, Martínez A, Villamor N, Ghita G et al.
Comparison of four prognostic scores in peripheral T-cell lymphoma. Ann Oncol 2011;22:397-404.
Dogan A, Morice WG. Bone marrow histopathology in peripheral T-cell lymphomas. Br J Haematol 2004;127:140-54.
Chott A, Augustin I, Wrba F, Hanak H, Ohlinger W, Radaszkiewicz T. Peripheral T-cell lymphomas: A clinicopathologic study of 75 cases. Hum Pathol 1990;21:1117-25.
Vahid B, Machare-Delgado E, Marik PE. Pulmonary manifestations of peripheral T-cell lymphoma: Case report and review of the literature. Clin Respir J 2007;1:114-7.
Fraser T, Nagarur A. Pulmonary involvement of peripheral T-cell lymphoma manifesting as crazy paving pattern. Proc (Bayl Univ Med Cent) 2015;28:59-61.
Schowalter MK, Akilov OE, Story SK, Geskin LJ. Cutaneous manifestations of unspecified peripheral T-cell lymphoma may be indicative of disease activity and predict response to therapy. J Clin Oncol 2012;30:e283-5.
Foss FM, Zinzani PL, Vose JM, Gascoyne RD, Rosen ST, Tobinai K. Peripheral T-cell lymphoma. Blood 2011;117:6756-67.
[Figure 1], [Figure 2]