Disappointing Outcomes of Peripheral T Cell Lymphoma after Autologous Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5428-5428
Author(s):  
Stephen D. Smith ◽  
John William Sweetenham ◽  
Lisa Rybicki ◽  
Stacey Brown ◽  
Robert M. Dean ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Lymphoma ◽  
Patient Characteristics ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Peripheral T Cell Lymphoma ◽  
First Remission ◽  
Alk Positive

Abstract The role of high dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell NHL following HDT have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Older retrospective studies found comparable survival rates after ASCT for pts with T-cell and B-cell NHL.1,2 In this study, we report our single center experience over one decade using a uniform high-dose regimen for patients with PTCL. Patients and Methods The transplant database of the BMT program at Cleveland Clinic was reviewed, and 32 patients undergoing ASCT for PTCL between 1996 and 2005 were identified. Twenty-one patients (66%) had anaplastic large cell lymphoma (ALCL), and 11 (34%) had peripheral T cell, not otherwise specified (PTCL-NOS). Patient characteristics are summarized in table 1. Stem cell mobilization with VP16 and GCSF priming provided a median CD34 cell dose of 5.01× 106/kg (range 2.05–29.69). Patients received a preparative regimen consisting of busulfan (either 1 mg/kg orally or 0.8mg/kg IV for 14 doses), followed by VP16 60 mg/kg IV continuous infusion, then cyclophosphamide 60mg/m2 IV daily for two days. Standard supportive care measures were employed. Results Recovery to 500 neutrophils/uL occurred at a median of 10 days post transplant (range 9–12 days) and platelet recovery to 20 000 at a median of 14 (range 7–60) days. Kaplan-Meier 5 year overall survival and relapse-free survival for all patients is 34% and 18%, respectively; median survival for all patients is 36 months (see figure 1). Median follow-up of 10 survivors is 25 months. No obvious plateau was observed on the overall or relapse fee survival curves. No significant difference in outcomes based on subgroup (ALCL versus PTCL-NOS) was observed. Staining for anaplastic lymphoma kinase (ALK) was available for 11 (of 21 total) anaplastic T cell lymphoma patients: 4/5 ALK-positive patients are alive compared to 2/6 ALK-negative patients at last follow-up. Four of five patients undergoing ASCT as consolidation following initial therapy are alive at a median 25 months. Based on this small patient population, and in contrast to some recent studies, our results suggest a poor outcome for patients with PTCL after ASCT. The outcome for pts undergoing ASCT in first remission, and for ALK-positive (versus ALK-negative) ALCL, requires prospective investigation. Table 1: Patient Characteristics Characteristic N (%) ALCL 21 (66) PTCL NOS 11 (34) Male 21 (66) Age: median(range) 44 (16-69) 2 prior chemo regimens 22 (69) 3 or more prior chemo regimens 7 (22) Transplant in first remission 5 (16) Relapsed/Refractory 25 (78) Figure Figure

Hyperchidam Verona897 Regimen Is Effective in Treatment of Advanced Peripheral T Cell Lymphoma (PTCL): The GITIL Experience in 33 Cases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4465-4465
Author(s):  
Giuseppe Todeschini ◽  
Paolo Corradini ◽  
Sergio Cortelazzo ◽  
Alessandro Rambaldi ◽  
Andrea Gallamini ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Peripheral T Cell Lymphoma ◽  
Intensive Regimen

Abstract Background. Peripheral T cell Lymphoma (PTCL) represent a major therapeutic challenge. In the previous Verona experience (Todeschini G et al. Cancer2005;104:555–560), the novel intensive regimen HyperCHiDAM Verona897 (high-dose IV MTX 2 g/sqm 400 sqm bolus, 1600 sqm CI day 1 with IV leucovorin rescue; hyperfractionated IV CTX 300 mg/sqm Q12h, dd 2–4; high-dose IV AraC 2g/sqm Q12h, dd 2-4; plus G-CSF) achieved salutary results in refractory/relapsed aggressive lymphomas, in particular in PTCL. Supportive measures included hydratation 3000 ml/sqm/day, antimicrobial prophylaxis comprising oral ciprofloxacin, itraconazole, trimethoprim/sulfamethoxazole. CMV antigenemia (pp65) was monitored 2 times a week. Patients. Following these results, 7 centers belonging to the Italian co-operative group GITIL (Gruppo Italiano Terapie Innovative Linfomi) treated with 2 cycles of HyperCHiDAM Verona897, 33 patients affected by PTCL (17 upfront, 16 refractory/relapsed) followed in the majority of cases by stem cell transplant. Patients: M/F 21/12, median age 49 (19–63) years; histology: PTCL-NOS 15, ALCL ALK-negative 9, EALTC 4, AIL 3, T-NK nasal 1, Angiocentric 1; stage IV 19/33 (57.5%), bone-marrow positive 10/33 (30.3%), extranodal involvement 24/33 (72.7%), high LDH 18/33 (54.5%). Seven patients needing urgent treatment were treated before HyperCHiDAM with 1 cycle of Campath-CHOP (4 patients) or CHOP + L-ASE (3 patients). Results. Upfront patients: after 2 cycles of HyperCHiDAM, CR were 82.3% (14/17), early toxic deaths 0 (1 late toxic death occurred after SCT, due to CMV pneumonia), relapses 3/14. With a median follow-up of 21 months (3–90+), 11/17 (64.7%) patients are disease-free, 10 in first CR, 1 after rescue with stem cell transplant. Three of the CCR patients received HyperCHiDAM alone. Refractory/relapsed patients: CR were 5/16 (31.2%), CCR 4/16 (25%), with a median follow-up of 24 months (5–64+). The progression-free survival was significantly superior in upfront patients (p=0.036). Overall, toxic deaths were 3/33 (9%), 1/17 (5.8%) in upfront and 2/16 (12.5%) in refractory/relapsed patients. One patient had major cerebellar toxicity. Conclusions. The intensive regimen HyperCHiDAM Verona897 is effective in inducing CR in aggressive PTCL, in particular as upfront therapy. The intensiveness of this treatment requires a careful supportive therapy. Following these results, HyperCHiDAM has been included in a national trial for treatment of PTCL, after 2 cycles of Campath-CHOP and before stem cell transplant (allogeneic or autologous depending on the availability of an HLA-matched sibling). The co-operative study is recruiting.

Aggressive Primary Chemotherapy Plus Autologous Stem Cell Transplantation Improves Outcome for Peripheral T Cell Lymphomas Compared with CHOP-Like Regimens.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1660-1660 ◽  
Author(s):  
Michal Sieniawski ◽  
James Lennard ◽  
Christopher Millar ◽  
Simon Lyons ◽  
Philip Mounter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Alk Positive

Abstract Abstract 1660 Poster Board I-686 Background In the past two decades we have observed improvement in the outcome of patients diagnosed with some subtypes of lymphoma. However, the prognosis of patient with peripheral T-cell lymphoma (PTCL) still remains unsatisfactory. We prospectively evaluated aggressive chemotherapy and autologous stem cell transplantation (ASCT): IVE/MTX-ASCT in patients with de-novo PTCL. Patients and methods: The regimen was piloted from 1997 for new patients eligible for intensive treatment: first for pts with enteropathy associated T-cell lymphoma (EATL) and subsequently for other types of PTCL. This therapy delivers one cycle of CHOP, followed by 3 courses of IVE (ifosfamide, etoposide, epirubicin), alternating with intermediate dose methotrexate (MTX). Stem cells are harvested after IVE and complete remissions (CR) were consolidated with myeloablative ASCT. The patients were evaluated with an intent to treat analysis for feasibility, response, progression free survival (PFS) and overall survival (OS). Results 57 patients were treated with the aggessive regimen, 26 pts had EATL and 31 other types of PTCL: 17 peripheral T-cell lymphoma NOS, 6 anaplastic T-cell lymphoma ALK positive, 4 extranodal NK/T cell lymphoma nasal type, 3 anaplastic T-cell lymphoma ALK negative and 1 hepatosplenic gamma/delta T-cell lymphoma. The median age at diagnosis was 51 years (range 23 – 69), 36/57 (63%) pts were male and 27/55 (49%) presented with ECOG >1. Early stage disease was diagnosed in 22/57 (39%) pts and advanced disease in 35/57 (61%). Bone marrow was involved in 6/53 (11%) pts and LDH was elevated in 23/46 (50%). Among pts with primary nodal disease 14/26 (54%) had at least one extranodal site involved and 6/26 (23%) bulky disease. At present, 55 pts are available for response evaluation. Eight pts discontinued treatment prematurely; 4 due to toxicity (one severe sepsis and death, one severe encephalopathy, one bone marrow failure and one bleeding from the gastrointestinal tract), and four pts due to disease progression. Of the remaining 47 pts 33 went on to receive ASCT. ASCT was omitted due to: refractory disease in 5 pts, poor general condition in 4 pts, insufficient stem cell mobilisation in 4 pts and one pt declined further treatment. The most common severe toxicities were pancytopenia, infection, nausea/vomiting and obstruction/perforation. Complete remission was confirmed in 39/55 (71%) pts, partial remission in 3/55 (5%) pts and 13/55 (24%) pts failed the treatment. The remission rates were: CR-17/26 (65%) pts and PR-1/26 (4%) for EATL and 22/29 (76%) and 2/29 (7%), respectively for other PTCL. During the study time 17/57 (30%) pts died, 15 due to lymphoma. For all pts 3-years PFS was 59% and OS 67%. For pts with EATL the 3-years PFS and OS were 52% and 60% and for other types 65% and 72%, respectively. These results were unchanged after the exclusion of anaplastic T-cell lymphoma ALK positive: (61% and 72%, respectively). Conclusions For patients with PTCL, we propose that intensive chemotherapy and ASCT significantly improves outcome compared to CHOP-like regimens, and has acceptable toxicities. In conclusion, where feasible patients with PTCL should be considered for aggressive treatments, like IVE/MTX – ASCT as primary therapy. Disclosures No relevant conflicts of interest to declare.

Update of a phase II, multicenter study of high-dose chemotherapy with autologous stem cell transplant followed by maintenance romidepsin for T-cell lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7533-7533
Author(s):  
Niloufer Khan ◽  
Farhad Khimani ◽  
Andrei R. Shustov ◽  
Mazyar Shadman ◽  
Jia Ruan ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Multicenter Study ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem

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]

Stem Cell Transplant (SCT) and Pralatrexate Therapy: Outcome of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma Who Received SCT Prior to or Following Pralatrexate Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3420-3420
Author(s):  
Leslie Popplewell ◽  
Barbara Pro ◽  
Eric Jacobsen ◽  
Steven M. Horwitz ◽  
Adam Boyd ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Peripheral T Cell Lymphoma ◽  
Additional Therapy

Abstract Abstract 3420 Poster Board III-308 Background Stem cell transplant (SCT) may be offered as a curative approach in patients with chemotherapy-sensitive peripheral T-cell lymphoma (PTCL). Thus, new agents with the ability to induce a response for relapsed or refractory patients are important to identify. This analysis evaluated SCT use before or after pralatrexate, a new anti-folate, as monotherapy in the PROPEL study. Methods Patients with relapsed or refractory PTCL received pralatrexate 30 mg/m2 by IV push once weekly for 6 weeks in 7-week cycles with vitamin B12 and folic acid supplementation in PROPEL. Eligibility criteria included histologic confirmation of PTCL by central review, disease progression after ≥ 1 prior treatment, and ECOG performance status £ 2. Response was assessed centrally using the International Workshop Criteria. Patients who had received prior allogeneic SCT were not permitted to enroll. Patients with prior autologous SCT were eligible if they had not relapsed within 75 days of SCT. There were no restrictions on SCT after completing study treatment. Subsequent post-pralatrexate therapies were recorded during follow up until patient death, loss to follow-up, or data cutoff. Results One-hundred and nine patients in the PROPEL trial were evaluable for response. Eighteen (16%) had received autologous SCT previously, including 8 (7%) patients for whom SCT was the most recent therapy prior to study enrollment. The overall response rate (ORR: complete response [CR/CRu] or partial response [PR]) was 33% (6/18), including 2 CRs, for patients with a prior autologous SCT at any time prior to receiving pralatrexate and 63% (5/8), including 2 CRs, for those patients whose most recent therapy was autologous SCT. Patients were followed from initiation of pralatrexate for a median of 10.5 months (range, 1.0-24.0). Of the 109 patients who were evaluable for response, 6 (6%) patients went on to SCT (2 autologous SCT, 4 allogeneic SCT) as their initial subsequent therapy after responding to pralatrexate according to investigator assessment of response. Four of these patients were still in response by central review at the time they started SCT. At the time of data cutoff, no additional therapy was administered to any of these 4 patients post SCT. The other 2 patients had PRs by investigator review and progressive disease by central review at the time SCT was started; neither of these patients had additional therapy documented after SCT. All 6 patients were alive at the time of last contact. Conclusions The PROPEL trial showed that pralatrexate as a single agent had activity, including CRs, in patients who relapsed following an autologous SCT. The PROPEL trial also demonstrated that patients with relapsed or refractory PTCL can proceed to subsequent SCT after achieving a response with pralatrexate, permitting these patients a transplant option and potential cure. Disclosures Pro: Allos Therapeutics, Inc.: Research Funding. Jacobsen:Allos Therapeutics, Inc.: Consultancy. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding. Boyd:Allos Therapeutics, Inc.: Employment. Fruchtman:Allos Therapeutics, Inc.: Employment.

The Role of High Dose Chemotherapy/Autologous Stem Cell Transplantation for Salvage Treatment for Relapsed Peripheral T Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4363-4363
Author(s):  
Yoojin Cho ◽  
Myoung Joo Kang ◽  
Dae Ro Choi ◽  
Eun Kyoung Kim ◽  
Shin Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Peripheral T Cell Lymphoma

Abstract Abstract 4363 Introduction Although the role of high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in the treatment of aggressive lymphoma has been established, optimal second line treatment, including high-dose therapy with autologous stem cell support, is not well established in patients with peripheral T cell lymphoma (PTCL). The purpose of this retrospective study was to compare the outcome of salvage chemotherapy only with that of HDCT and ASCT in patients with relapsed disease after having reaching a complete response (CR). Methods We retrospectively investigated the outcome of salvage treatments for patients with relapsed PTCL who had reached a CR. Results Between January 1999 and February 2009, 39 patients (15 peripheral T cell lymphoma; 14 extranodal natural killer/T cell lymphoma; 5 anaplastic large cell lymphoma; and 6 angioimmunoblastic T-cell lymphoma) were identified to be eligible for this analysis in our institution. Among them, 25 were treated with only salvage chemotherapy and 14 were treated with HDCT/ASCT. The salvage chemotherapy regimens were ESHAP given in 52% and DHAP given in 12%. Also the conditioning chemotherapy regimens for autologous stem cell transplantation (ASCT) were ESHAP given in 50% and DHAP given in 14.2%. The median number of chemotherapy regimen was 3. The overall response rate of salvage chemotherapy was 92% with a CR rate of 50%. With median follow-up time of 20.7 months, there were no statistical differences between the two groups in terms of progression-free survival and overall survival (p=0.794, and p=0.390, respectively). Conclusion There were no significant differences between the two groups in terms of survival outcome. Therefore, considering the dismal outcome in relapsed PTCL patients even after treated with HDCT/ASCT, incorporation of novel therapeutics into a treatment regimen should be considered. Disclosures: No relevant conflicts of interest to declare.

Response at Interim Evaluation Predicts Survival after Autologous Stem Cell Transplantation in Nodal Peripheral T-Cell Lymphoma; A Nordic Lymphoma Group Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1830-1830
Author(s):  
Fredrik Ellin ◽  
Knut Liestøl ◽  
Susanna Mannisto ◽  
Grete F Lauritzsen ◽  
Esa Jantunen ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Peripheral T Cell Lymphoma

Abstract Introduction: In the Nordic Lymphoma Group trial NLG T-01, patients with newly diagnosed peripheral T-cell Lymphoma (PTCL) were treated with six courses of CHOEP (up to 60 yrs) or CHOP (61-67 yrs) followed by high-dose chemotherapy (BEAM) and autologous stem cell transplantation (ASCT). At 5 years median follow-up, the progression-free survival of the trial cohort was 44%. On this background, the NLG-T01 treatment strategy has become the recommended first-line treatment for younger fit patients in the Nordic countries and in the latest ESMO guidelines for PTCL. Despite this intensive approach with up-front ASCT a fraction of patients still relapses. In an attempt to find factors predictive for survival after up-front ASCT we aimed to analyze the impact of radiologic response at the first interim evaluation on long-term survival. Methods: All NLG T-01 patients (TrialP) with "nodal" PTCL, i.e. anaplastic large cell lymphoma, ALK-negative (ALCL), angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma not otherwise specified (PTCL NOS), that actually received the planned ASCT were included. Using national (Sweden and Denmark) or site-specific (Finland and Norway) registries, additional patients (RegP) who received the same treatment schedule, but off-protocol, were identified, and data for these patients was collected retrospectively. Overall survival (OS) was calculated from date of stem cell reinfusion until death from any cause. The first interim computed tomography (iCT) scan was performed after 3 cycles of chemotherapy. Response assessment in the NLG-T-01 trial was based on the 1999 International Working Group criteria for response, which allowed for complete remission unconfirmed and these patients have been grouped with CR in the present analysis. Progressive Disease (PD) was defined as increase of ≥25% of any lesion. Results: Altogether, 132 patients were included in the present study (TrialP n= 92; RegP n=40). The clinical characteristics are presented in the Table. The 5-year OS among all the patients was 58%. Response at iCT was CR, partial remission (PR) and SD in 44%, 53% and 3% respectively. Of the four patients with SD at iCT, all four patients attained PR after completing six cycles of chemotherapy prior to ASCT. Kaplan-Meier estimates for OS are illustrated in the Figure and the 5-year OS was identical, 61%, for patients in CR and PR but 0%for patients with SD. Using log-rank comparisons patients achieving SD at iCT had a significantly worse survival compared to patients with CR or PR (p=.01). Discussion: This study is to our knowledge the first to analyze whether interim treatment response can predict long-term OS in "nodal" PTCL patients treated with CHOEP or CHOP consolidated by up-front ASCT. Patients with SD after three cycles of chemotherapy had a very poor survival compared to patients with PR or CR. This was an expected finding, and it confirms the importance of chemo-sensitive disease as a necessary pre-requisite in order to benefit from up-front high-dose consolidation. Using CT, there was no survival difference between patients with CR or PR at the first interim evaluation. A larger cohort might reveal further differences in subgroups, particularly if PET/CT based remission evaluation should confirm itself as a useful tool also in nodal PTCL. At present our study indicates that failure to achieve PR after three cycles of CHOEP/CHOP identifies patients at high risk of relapse/progression that are in need of a different therapeutic strategy than continuing with CHOEP/CHOP towards an ASCT. Table Table. Figure Figure. Disclosures Mannisto: Gilead: Other: Travel expenses; Celgene: Other: Travel expenses; Novartis: Other: Travel expenses; Amgen: Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses; Roche: Honoraria, Other: Travel expenses; Pfizer: Honoraria; SOBI: Honoraria.

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