Role of Front-Line High Dose Therapy with Stem Cell Transplant in Peripheral T-Cell Lymphomas. A Single Center Experience.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2733-2733
Author(s):  
Giuseppe Gritti ◽  
Andrea Rossi ◽  
Anna Maria Barbui ◽  
Anna Grassi ◽  
Alessandra Algarotti ◽  
...  

Abstract Abstract 2733 Introduction: The best treatment of peripheral T-cell lymphomas (PTCLs) currently remains a matter of debate. Some retrospective study and few phase II trials have shown that first line high dose therapy (HDT) with autologous stem cell transplant (SCT) may apparently offer better results. However, no comparative trials are currently available. Material and Methods: We retrospectively evaluated the outcome of previously untreated patients with PTCL, excluding mycosis fungoides and Sézary syndrome, referred to our Center between 1996 and 2012. An in-house histologic revision was performed to confirm the diagnosis according to the latest WHO criteria. From this analysis we excluded patients with diagnosis of ALK positive anaplastic large cell lymphoma (ALCL). We stratify patients according to treatment. Conventional therapy (CT) consisted of CHOP, CHOEP or MACOP(-B). From early 90s at our Center was adopted the strategy to consolidate response to initial treatment with either autologous or allogeneic SCT, whenever possible, in patients aged <65 years. These patients were assigned to HDT group. Results: The specific diagnosis of the 124 patients evaluated was PTCL-not otherwise specified (n=70), angioimmunoblastic T-cell lymphoma (n=21), ALCL ALK negative (n=19), other subtypes (n=14). At diagnosis, 43 patients were planned to receive HDT plus SCT but only 26 (60%) eventually received it (22 autologous, 4 allogeneic) while the remaining experienced early death (8 patients), progression (8 patients) or mobilization failure (1 patient). The median age of this first cohort was 47.9 years (range 23–63), that also showed an advanced Ann-Arbor stage (III-IV) or an int-high/high IPI in 77% and 58% of the cases, respectively. The rate of complete remission (CR) was 57% with 21% of patients dying during treatment (5 patients not evaluable for response, 3 responders and 1 with progressive disease). Eighty-one patients were treated according to a CT strategy. The median age of this latter group was 66.7 years (25–85), an advanced stage (III-IV) or an int-high/high IPI was present in 73% and 61%, respectively. The CR rate was 57% with 19% of the patient dying during treatment (11 patients not evaluable for response, 2 responders and 1 with progressive disease). With a median follow up of 1.63 years (0–25) and 82 deaths, by intention to treat analysis the 5-years overall survival (OS) was 43% and 32% for HDT and CT (p=.90, figure 1), respectively, while the 5-years OS of those patients eventually receiving SCT was 64%. Irrespectively from the adopted treatment strategy, patients who achieved a CR showed a similar 5-years OS and disease free survival that were 57% and 52% in the CT group and 80% and 64% in the HDT cohort (p=.43 and p=.44), respectively. Of the 54 patients with relapsed or refractory disease, 9 underwent salvage SCT (4 autologous, 5 allogeneic) with 3 patients achieving a sustained remission. Conclusions: The overall clinical outcome of most PTCL patients remains unsatisfactory, with a large fraction of patients not responding to front-line treatment. The advantage of a post-remission consolidation with SCT has to be confirmed by appropriate ad hoc designed clinical studies. On the contrary, allogeneic SCT, despite remaining a potentially curative treatment option for these patients, unfortunately has a limited applicability due to the frequent advanced age and comorbidities as well as to the difficulty in finding a donor. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2679-2679 ◽  
Author(s):  
Steven Horwitz ◽  
Craig Moskowitz ◽  
Tarun Kewalramani ◽  
Paul Hamlin ◽  
David Straus ◽  
...  

Abstract Background: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with a poorer prognosis than their B-cell counterparts. Second -line chemotherapy (SLT) followed by high dose therapy and autologous stem cell transplantation (HDT/ASCT) is a common approach to patients (pts) with relapsed PTCL. Reports evaluating this approach have analyzed the outcome of transplanted patients. Our goal was to identify pts with relapsed or refractory disease, treated in a uniform manner, with the intent to induce a remission and proceed to HDT/ASCT. Patients and Methods: From our ICE database we identified 40 pts with a diagnosis of a mature T or NK lymphoma who received ICE as SLT therapy prior to planned HDT/ASCT. Histologic subtypes were as follows: PTCL NOS (n=15), anaplastic large cell lymphoma (n=11), angioimmunoblastic T-cell lymphoma (n=5), NK/T cell lymphoma (n=4), subcutaneous panniculitis-like T-cell lymphoma (n=2), and one each of hepatosplenic γ/δ T-cell lymphoma, enteropathy associated T-cell lymphoma, and transformed mycosis fungoides. Median age was 48 years (24–73), five pts were ≥ 60 years. Twenty-five men and 15 women were treated. Initial chemotherapy regimens included: CHOP/CHOP-like (n=32), NHL-15 (n=5), and other (n=4). Twenty-two pts responded to their initial therapy and 18 had primary refractory disease. At time of relapse, 24 pts had stage IV disease, 23 had elevated LDH, and 9 had a performance status ≤ 70%. Thirty-one pts had at least one extranodal site. Complete second line International Prognostic Index (IPI) factors (AA stage, LDH, PS) were available for 36 pts. IPI scores were LR (n=3), LIR (n=12), HIR (n=13), and HR (n=8). Results: All pts received at least one cycle of ICE, 36 received all three planned cycles. Fourteen patients (35%) achieved a complete response, 14 (35%) had a partial response, four (10%) had stable disease, and eight (20%) progressed on therapy. Twenty-seven (68%) pts went on to receive HDT/ASCT. Median follow-up for surviving pts was 45 months (range 7–104). By 3 years, 33/40 (83%) of pts had relapsed with a median progression free survival (PFS) of 6 months from last ICE treatment. Twenty-eight (70%) pts relapsed within 1 year. Neither second-line IPI nor histologic subtype was predictive of continuous remission. Relapsed pts had a superior 3 year PFS compared to primary refractory pts 20% vs 6% (p=0.0005). Despite high relapse rate, 18/40 (45%) of pts were alive at last follow-up. Conclusion: SLT and HDT/ASCT is a common treatment strategy for pts with relapsed PTCL. However, when examined by intention to treat from initiation of SLT and not from time of transplant few pts have durable benefit from this approach. Despite the high response rate to SLT, consolidation with HDT/ASCT provides little clinically meaningful benefit for most pts. The number of pts alive with other therapies despite early relapse underscores the need to study alternative or maintenance strategies for those who achieve remissions.


2004 ◽  
Vol 45 (11) ◽  
pp. 2261-2267 ◽  
Author(s):  
Madan Jagasia ◽  
David Morgan ◽  
Stacey Goodman ◽  
Katherine Hamilton ◽  
Marsha Kinney ◽  
...  

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Y. Y. Hwang ◽  
R. H. S. Liang

T-cell lymphoma is a heterogeneous group of diseases. Except for ALK positive anaplastic large cell lymphoma, T-cell lymphoma responds to conventional chemotherapy unfavourably, and most patients carry poor prognosis. In recent years, efforts have been made to improve the outcome of T-cell lymphoma patients. Novel agents, high-dose therapy, and allogeneic stem cell transplantation are studied, and various results are reported in literature. This paper looks into the prognostication and treatment approach of different entities of noncutaneous T-cell lymphoma and would focus on the latest updates in its management.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7533-7533
Author(s):  
Niloufer Khan ◽  
Farhad Khimani ◽  
Andrei R. Shustov ◽  
Mazyar Shadman ◽  
Jia Ruan ◽  
...  

7533 Background: Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes with conventional chemotherapy. Autologous hematopoietic stem cell transplant (AHCT) is a therapeutic strategy for patients in first complete or partial remission (CR1 or PR1), with median progression-free survival (PFS) after AHCT of 36-48% by intent to treat (d’Amore et al JCO 2012, Reimer et al JCO 2009). Romidepsin (romi) is a histone deacetylase inhibitor approved for treatment of relapsed/refractory T-cell lymphoma. We present updated data of the first multicenter study to evaluate PFS of patients (pts) receiving maintenance therapy with romi after AHCT. Methods: This was a phase 2, open-label, investigator-initiated study (expected PFS 45%, desired PFS 70%; success achieved if 15 or more pts out of 25 were progression-free at 2 years post-AHCT). 26 pts transplanted in CR1 or PR1 were evaluable for the primary endpoint of 2-year PFS (Cohort 1, Table). An exploratory cohort (Cohort 2, n=7) enrolled pts either transplanted ≥ CR/PR2 (n=5) or with high risk histologies (n=2). Pts underwent AHCT with carmustine, etoposide, cytarabine and melphalan (BEAM) conditioning. Maintenance romi 14 mg/m2 started days 42-80 post AHCT; every other week through 6 mon, every 3 weeks through 1 year and every 4 weeks through 2 years post AHCT. PFS was estimated by Kaplan-Meier. Results: 47 pts consented; 13 did not receive romi (no AHCT, n=2; relapse before romi, n=3; cardiac comorbidity, n=3, patient declined, n=5). 1 consented pt did not have PTCL. 15 out of the first 25 pts in Cohort 1 were progression free after 2 years; median follow up of 31 mon (21 - 36 mon). Estimated 2-year PFS was 62% (45-83%, 95% CI); median PFS 30 mon (12.0- NA, 95% CI). In Cohort 2, estimated 2-year PFS was 43% (18 – 100, 95% CI); median follow up of 30 mon (range, 24 – 37 mon); median PFS 14 mon (5 – NA, 95% CI). Across cohorts, 5 pts required dose reduction. The most common toxicities (≥10% of pts, all grades) were fatigue (n=24, 73%), decreased platelets (n=16, 48%) and anemia (n=16, 48%). Conclusions: While the study did not meet its desired primary efficacy endpoint, maintenance romi was well-tolerated with an estimated 2-year PFS of 62%, greater than historical data. A larger, randomized study would be needed to determine the superiority of this approach. Clinical trial information: NCT01908777. [Table: see text]


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 904-904 ◽  
Author(s):  
Peter Reimer ◽  
Thomas Ruediger ◽  
Tobias Schertlin ◽  
Eva Geissinger ◽  
Florian Weissinger ◽  
...  

Abstract Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of non-Hodgkin’s lymphomas, which in general show a poor outcome following conventional chemotherapy. Long-term remissions are achieved in only 15 to 35 %. However, the impact of more aggressive therapeutic approaches such as myeloablative therapy with autologous stem cell transplantation (ASCT) as first line therapy is poorly defined mainly due to the lack of prospective PTCL-restricted studies. In 6/00 we initiated the first prospective PTCL-restricted multicenter study of myeloablative radiochemotherapy in primary diagnosed PTCL. The results of the first 30 patients (pts) are in press. We update our data on all pts entering the study. Study design: Pts < 65 years with PTCL of all subtypes without primary cutaneous lymphoma and ALK1 expressing anaplastic large cell lymphoma were included. Treatment consisted of 4–6 courses of CHOP protocol followed by DexaBEAM or ESHAP regimen and collection of stem cells. Subsequently pts underwent total body irradiation (TBI) and high dose cyclophosphamide chemotherapy (60 mg/kg body weight) with ASCT. Patient characteristics: From 6/00 to 8/04 65 pts (42 male) with a median age of 50 years were enrolled. Main subtypes were Peripheral T-cell lymphoma not otherwise specified (NOS, n= 26) and Angioimmunioblastic T-cell lymphoma (AILT, n= 19). According to the Ann Arbor classification, 81% of the pts had stage III/IV disease. The International Prognostic Index (IPI) was low/low intermediate in 54% and intermediate high/high in 46% of the pts, respectively. Results: So far 54 of 65 pts are eligible for evaluation, while the remaining 11 pts are still under therapy. Thirty-three pts could be transplanted (61%). After a median follow up of 10 months after transplantation 22 pts (67%) are in sustained remission and 8 pts (27%) had relapsed. Post transplantation two pts died treatment-related (one secondary AML, one multiorgan failure). Twenty-one pts (39%) did not proceed to ASCT mainly due to progressive disease (n= 16). Treatment-related toxicity was comparable to other high-dose studies in malignant lymphomas. Conclusion: Our data show feasibility and efficacy of first-line ASCT following myeloablative radiochemotherapy in PTCL. Sustaining remission seems achievable for a majority of pts. However, additional treatment strategies are required to prevent early progression prior myeloablative therapy. Longer follow-up is necessary to confirm long-term remission rate.


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.


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