Clinical Features and Outcome of Relapsed Refractory Aggressive Peripheral T-cell Lymphoma- A Ten-Year Study From A Single Institute In India TVSVGK Tilak, Lalit Kumar, Atul Sharma, Sameer Bakhshi, Ranjit Kumar Sahoo, Smita Kayal, Surendra Chaudhary, Vinod Raina Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India Background RADIOLOGICAL FEATURES Contrast enhanced imaging was performed in 36 patients. CT chest was abnormal in 20 (30.7%) and CT abdomen was abnormal in 25 (38.5%). TREATMENT Of the 65 patients, 40 (61.5%) received a second-line regime. The remaining patients were either not fit for any chemotherapy, opted out of treatment or went elsewhere for further management. The various regimes were exhibited to the remaining 40 patients are detailed in Table-3. Relapse or progression is a major determinant of outcome despite initial response to therapy in aggressive peripheral T-cell NHL (PTCL). There is paucity of data on outcome of relapsed/refractory patients of aggressive PTCL as there are limited treatment options at relapse. We analyzed the clinical features and outcome to second-line therapy of patients with aggressive PTCL. Material and Methods Table-3: Salvage Regimes Salvage Regimes Number of patients (%) Untreated 25 (38.4%) Treated 40 (61.5%) MINE 10 (15.3%) ICE 7 (10.7%) DHAP Others BFM-90 Hyper-CVAD Single agent Vinblastine Metronomic therapy 16 (24.6%)   Medical records of all cases of T-NHL that were registered at out hospital [Institute Rotary Cancer Hospital (IRCH) of All India Institute of Medical Sciences (AIIMS)] over a ten year period from January 2002 to July 2011 were retrieved. Of the total of 302 T-NHL patients registered during this period, a total of 65 patients of relapsed/refractory T-NHL were included in this study. Files were reviewed for demographics, baseline patient characteristics, laboratory parameters and imaging findings. Systemic work-up included detailed clinical evaluation (history and physical examination including baseline ECOG performance status). The diagnosis of relapse was confirmed by trucut biopsy and/or fine needle aspiration cytology (FNAC) of the representative lymph node/mass along with immunohistochemistry. RESPONSE TO SALVAGE THERAPY AND SURVIVAL Complete remission to second-line regimes was achieved in six (9.2%), while 12 (18.4%) achieved partial response and one had stable disease. Autologous stem cell transplant (ASCT) was offered to five patients, one of whom underwent transplant upfront as salvage modality. One patient died and the remaining four are alive in CR. Overall, 22 (33.9%) patients progressed at various time periods during and after second-line therapy/stem cell transplantation. Eight patients were alive at last follow up. Ten patients were lost to follow up. The median event-free survival (EFS) of the entire cohort was 9.9 months. The overall survival data would be inaccurate with a large proportion of patients not accepting second-line therapy or being lost to follow-up and hence was not estimated. PROGNOSTIC FACTORS Clinical (age, sex, ‘B’ symptoms, extranodal or bulky disease) and laboratory parameters (hemoglobin, albumin, LDH) affecting EFS were calculated using cox proportional hazards model. None of the factors could predict event-free survival. Statistical Methods The study design was retrospective analysis of files of patients for obtaining data. The data was censored on 30 Jun 2013 for survival analysis. Descriptive statistics were used for demographics and clinical characteristics. Survival was estimated by the Kaplan-Meier method and compared using log-rank test. Univariate Cox proportional hazard model followed by stepwise multivariate Cox regression analysis was done to identify the predictors of outcome. STATA/SE 9.0 (StataCorp LP, Texas, USA) was used for statistical analysis. Results PATIENT DEMOGRAPHICS The median age of the cohort of 65 patients was 45 yrs (range-1-86yrs). The male to female ratio was 3.6:1. Six (9.2%) patients were less than 18 years, 49 (75.4%) were in the age range of 18-60 yrs and 10 (15.3%) were over 60 years of age. HISTOPATHOLOGICAL FEATURES The histopathological diagnosis at baseline presentation of patients is outlined in Table-1. A major number of our cases were clubbed as T-NHL (unspecified) as exact characterization beyond T-cell was not feasible in the early part of the study due lack of antibodies for immunohistochemistry. Discussion T-cell lymphomas from India have been reported in the range of 15% of all NHLs. Of these the commonest is the precursor T-lymphoblastic lymphoma accounting for about 6% and the remaining peripheral T-cell lymphomas constitute 7-8%. (1) Geographical variation in the incidence of T-cell lymphomas has also been reported from India. Among our cohort of 65 patients, 60% had achieved CR to first-line therapy and the median duration of response after achieving complete remission was 4.9 months. The complete remission rates from western studies are in the range of 58-59%. (2) Peripheral T-cell lymphoma-NOS (PTCL-NOS) was the commonest subtype in the relapsed/refractory patients. Extranodal disease at presentation in nearly 55% of the cases and increased involvement of hepatosplenomegaly exemplifies the aggressive nature of the disease at relapse/progression. Treatment at relapse was feasible in only two-thirds of the cases. The regimes are not standardized as there are lack of guidelines in this area. Remission rates post salvage regimes are dismally low. Stem cell transplantation following salvage regime is known to improve the overall outcome in relapsed/refractory setting. (10,11) In our cohort stem cell transplant was offered to five patients which led to long term survival in four of these. In a Chinese study, IPI, LDH and stem cell transplantation were independent factors for survival. In our study we could not identify any clinical or laboratory marker affecting EFS. Table 1: Histopathological Diagnosis at Baseline Histopathological diagnosis Number of patients (%) Peripheral T-cell lymphoma-NOS 22 (33.8%) ALK-ve Anaplastic large cell lymphoma 7 (10.7%) Angioimmunoblastic T-cell lymphoma 4 (6.1%) NK/T-cell lymphoma ALK+ve Anaplastic large cell lymphoma 3 (4.6%) Subcutaneous panniculitis T-cell lymphoma 2 (3.0%) RESPONSE TO FIRST-LINE THERAPY Complete remission to first-line therapy was achieved in 39 (60%) patients. The median duration of complete remission in these patients was 4.9 months (range-1.2-80 months). CLINICAL FEATURES AT RELAPSE Table-2 gives the frequency of various clinical features at presentation. The commonest site of extranodal involvement included skin, seen in 10 (15.4%) patients. The other sites included bone (n=2), vertebral and spinal cord (n=2), CNS disease (n=2), ascites (n=2). Rare sites of extranodal involvement included chest wall, pleural effusion, PNS, oral cavity, orbit etc. References 1. Naresh KN, Srinivas V, Soman CS. Distribution of various subtypes of non-Hodgkin’s lymphoma in India: a study of 2773 lymphomas using R.E.A.L. and WHO Classifications. Ann Oncol Off J Eur Soc Med Oncol ESMO. 2000;11 Suppl 1:63–7. 2. Escalón MP, Liu NS, Yang Y, Hess M, Walker PL, Smith TL, et al. Prognostic factors and treatment of patients with T-cell non-Hodgkin lymphoma: the M. D. Anderson Cancer Center experience. Cancer. 2005 May 15;103(10):2091–8. 3. Yared J, Kimball A. The role of high dose chemotherapy and autologous stem-cell transplantation in peripheral T-cell lymphoma: A review of the literature and new perspectives. Cancer Treat Rev [Internet]. 2012 Apr 25 [cited 2012 May 27]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/22541889 4. Bertz H, Illerhaus G, Veelken H, Finke J. Allogeneic hematopoetic stem-cell transplantation for patients with relapsed or refractory lymphomas: comparison of high-dose conventional conditioning versus fludarabine-based reduced-intensity regimens. Ann Oncol. 2002 Jan;13(1):135–9. 5. Gao Y, Huang H-Q, et al. Treatment outcomes and prognostic analyses of relapsed or refractory T-cell non-Hodgkin’s lymphoma. Ai Zheng Aizheng Chin J Cancer. 2007 Aug;26(8):909–13. Table-2: Clinical Features at Relapse B Symptoms 29 (44.6%) Lymphadenopathy 41 (63%) > 2 LN Sites 19 (29.2%) Extranodal involvement 34 (52%) Bulky Disease 2 (3%) Liver Involvement 13 (20%) Splenic Involvement 16 (24.6%)