Superior Survival with Allogeneic Compared to Autologous Stem Cell Transplantation in Patients with Aggressive T Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 680-680
Author(s):  
Sivesh Kathir Kathir Kamarajah ◽  
Behrad Barmayehvar ◽  
Ali Z Gondal ◽  
Ram Malladi ◽  
Sridhar Chaganti

Abstract Introduction: Aggressive T-cell lymphomas often carry poor prognosis. With the exception of ALK+ anaplastic large cell lymphoma (ALCL), median survival for most entities is < 3 years from diagnosis. Whilst stem cell transplant (SCT) consolidation is sometimes used in an attempt to improve survival, its role remains controversial. Encouraging results have been reported with both autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) but it is unclear if one is better than the other. To inform this debate, we set out to examine outcomes of patients receiving SCT consolidation for aggressive T-cell lymphomas at our institute over a 10-year period (between 2005 Ð 2015), comparing results of ASCT versus allo-SCT. Methods: Review of our transplant database identified 59 patients receiving SCT for T-cell lymphomas between the years 2005 - 2015. We excluded 4 patients with low grade T cell lymphomas (mycosisfungoides/sezarysyndrome) from analysis. A further 4 patients were excluded as they had 2 SCT procedures (ASCT followed by an allo-SCT). Thus, 51 patients were eligible for analysis; all having received a single SCT procedure (either ASCT or allo-SCT) for treatment of aggressive T-cell lymphoma. Results: Median age of the entire cohort at the time of transplant was 54 years (range 18-72 years) with 39 male and 12 female patients. The most frequent histologies were: ALCL (n=13), angioimmunoblastic T cell lymphoma (n=10) and high grade T-NHL/ peripheral T-cell lymphoma (PTCL) not further classified (n=16).Thirty sevenof 51 patients had advanced (stage 3 or 4) disease. Median overall survival (OS) and progression free survival (PFS) for the entire cohort were 67 and 23 months respectively. All 30 patients receiving ASCT were conditioned with the BEAM regimen. Of the 21 patients receiving an allo-SCT, sixteen patients had reduced intensity conditioning and 5 myeloablative conditioning with cyclophosphamide and total body radiotherapy. Stem cell source was sibling donor in 11 and unrelated donor in 10patients.Nineteenpatients received a T-cell depleted graft (17 within vivo campath and 2 with ATG). The ASCT and allo-SCT groups were comparable for several baseline variables including tumour stage, LDH, performance status and presence of B symptoms. The allo-SCT cohort was younger with only 24% being over the age of 60 compared to nearly 47% in the ASCT group (median age 45 vs 56.5 years). The allo-SCT cohort had a higher risk disease with only 14 of the 21 patients (68%) being in 1st / 2nd remission at the time of transplant compared with 27 of 30 (90%) in the ASCT group. Furthermore, 16/21 (76%) patients in the allo-SCT cohort received >2 lines of treatment prior to transplant compared to only 2 (7%) in the ASCT cohort. Three patients in the allo-SCT (14%) and 2 in the ASCT (7%) groups were not in remission at the time of SCT. The 5-year OS for the allo-SCT cohort (68%) was significantly superior to the ASCT cohort (36%) (p=0.01). Median OS was significantly superior for the allo-SCT compared to the ASCT cohort (NR vs 21 months, respectively; p=0.03). The 5-year PFS for the allo-SCT cohort (62%) was significantly superior to that of the ASCT (34%) cohort (p= 0.03). The median PFS for the allo-SCT cohort was superior compared to the ASCT cohort (79 vs 17 months, p=0.083). On Cox regression multivariate analysis, disease status at the time of transplant (1st remission vs 2nd remission vs beyond 2nd remission vs not in remission) was significant for predicting both OS and PFS. Prognosis was dismal for those not in remission at the time of transplant with survival of <12 months. Transplant type (Allo vs auto) was significant for OS (HR 0.087, p=0.001) but not for PFS. Conclusion: Our data suggests allo-SCT may confer a survival benefit compared with ASCT for patients with aggressive T-cell lymphomas. This novel observation has not been reported previously and if validated in a larger cohort will be practice changing. Figure 1 Cumulative overall survival for the autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) cohorts. Figure 1. Cumulative overall survival for the autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) cohorts. Figure 2 Progression free survival for the autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) cohorts. Figure 2. Progression free survival for the autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) cohorts. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4672-4672
Author(s):  
Dipenkumar Modi ◽  
Seongho Kim ◽  
Abhinav Deol ◽  
Asif Alavi ◽  
Lois Ayash ◽  
...  

Abstract Introduction: Peripheral T-cell Lymphoma represents a heterogeneous group of lymphoid malignancies characterized by poor prognosis with 5-year overall survival (OS) about 25% with conventional chemotherapy. Autologous stem cell transplant (Auto-SCT), as consolidation, is often considered in first complete remission (CR), providing between 30 to 40% long term disease-free survival. However, patients receiving Auto-SCT in second CR or with refractory disease have poor outcomes with progression-free survival ranging from 15-20% to 0%, respectively. In such cases, allogeneic stem cell transplant (Allo-SCT) may provide long term disease control. We intended to study outcomes of Allo-SCT in peripheral T-cell lymphoma patients. Methods: We have retrospectively evaluated long-term outcomes of adult peripheral T-cell lymphoma patients at Karmanos Cancer Institute. The objectives were to determine GVHD rate, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following Allo-SCT. Results: Between January 2005 and December 2017, 39 patients underwent Allo-SCT. The different diagnoses included peripheral T-cell lymphoma, not-otherwise-specified (n=16), angioimmunoblastic T-cell lymphoma (n=8), anaplastic T-cell lymphoma (n=8), hepatosplenic T-cell lymphoma (n=2), cutaneous T-cell (n=3) and NK cell lymphoma (n=2). The median age at transplant was 50 years (range, 21-67). The median number of prior therapies was 2 (range, 1-5) and 12 patients (31%) had failed prior Auto-SCT. Sixteen patients (41%) were in CR and 2 (5%) were in partial remission at the time of Allo-SCT, whereas 12 (31%) patients had relapsed disease and 9 (23%) had refractory disease. Twenty-one patients (54%) received matched related and 18 patients (46%) had unrelated Allo-SCT. Myeloablative conditioning regimen was used in 22 patients (56%), whereas reduced intensity regimen was used in 17 (44%) patients. Grade III-IV acute GVHD occurred in 25.6% (95% CI, 13.2-40.1%) and chronic GVHD occurred in 41% (95% CI, 25.1-56.3%). After a median follow-up of 3.08 years (95% CI, 2.49-7.28) among surviving patients, the estimated probabilities of 3-year OS and PFS were 35.9% (95% CI, 22.4-57.6%) and 32.5% (95% CI, 19.9-53%), respectively. The 3-year relapse rate was 23.9% (95% CI, 11.5-38.7%), whereas NRM was 35.9% (95% CI, 21.1-50.9%). No difference in OS and PFS was noticed in patients receiving Allo-SCT in first CR compared with patients receiving Allo-SCT beyond first CR (p=0.81; p=0.94). Similarly, no difference in OS and PFS was noted in patients with Allo-SCT followed by failed prior Auto-SCT compared with patients with upfront Allo-SCT (p=0.31; p=0.47). Seventeen of 39 patients were alive and 22 were deceased (n=7 disease relapse; n=15 NRM). Out of 39 patients, 13 (33%) alive patients are free of relapse and GVHD as of data analysis. Conclusion: Our study suggests that Allo-SCT is a viable treatment option for peripheral T-cell lymphoma and appears to provide cure in these highly selected patients. The survival advantage was noted in patients beyond first remission; therefore, it should be considered in all transplant eligible patients. In addition, certain proportion of patients who failed prior Auto-SCT benefited from Allo-SCT, which points towards potential role of graft-versus-lymphoma effect. Disclosures Deol: Novartis: Consultancy; Kite Pharmaceuticals: Consultancy.


2020 ◽  
Vol 26 (3) ◽  
pp. S244
Author(s):  
Iris Isufi ◽  
Namrata Chandhok ◽  
Prajwal Boddu ◽  
Darko Pucar ◽  
Stuart E. Seropian ◽  
...  

2019 ◽  
Vol 83 ◽  
pp. 106171 ◽  
Author(s):  
Dipenkumar Modi ◽  
Malini Surapaneni ◽  
Seongho Kim ◽  
Lois Ayash ◽  
Asif Alavi ◽  
...  

2017 ◽  
Vol 96 (12) ◽  
pp. 2125-2126 ◽  
Author(s):  
Bhagirathbhai Dholaria ◽  
Raj J. Patel ◽  
Jason C. Sluzevich ◽  
Sikander Ailawadhi ◽  
Vivek Roy

Blood ◽  
2011 ◽  
Vol 117 (22) ◽  
pp. 5827-5834 ◽  
Author(s):  
Richard L. Piekarz ◽  
Robin Frye ◽  
H. Miles Prince ◽  
Mark H. Kirschbaum ◽  
Jasmine Zain ◽  
...  

Abstract Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL. This study has been registered at clinicaltrials.gov as NCT00007345.


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