scholarly journals Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma

Blood ◽  
2012 ◽  
Vol 119 (26) ◽  
pp. 6379-6381 ◽  
Author(s):  
Robert Chen ◽  
Joycelynne M. Palmer ◽  
Sandra H. Thomas ◽  
Ni-Chun Tsai ◽  
Len Farol ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Brentuximab Vedotin ◽  
Free Survival ◽  
Refractory Hodgkin Lymphoma ◽  
Reduced Intensity

Brentuximab vedotin induces an overall response rate of 75% in patients with relapsed/refractory Hodgkin lymphoma, but its impact on future allogeneic transplantation (allo-HCT) is not known. We retrospectively examined the records of 18 patients with relapsed/refractory Hodgkin lymphoma who were treated on brentuximab vedotin clinical trials to evaluate the efficacy and safety of subsequent reduced-intensity allo-HCT. Seventeen patients had previous autologous transplant; 6 were in complete remission, and 8 were in partial remission before allo-HCT with 12 grafts from unrelated or mismatched donors. The 1-year overall survival was 100%, progression-free survival was 92.3%, and nonrelapse mortality was 0% (median follow-up, 14 months). The incidence of acute GVHD was 27.8% and chronic GVHD was 56.3%. Brentuximab vedotin before reduced-intensity allo-HCT does not appear to adversely affect engraftment, GVHD, or survival and may provide sufficient disease control to enable reduced-intensity allo-HCT.

scholarly journals Brentuximab Vedotin Is Associated with Improved Progression-Free Survival after Allogeneic Transplantation for Hodgkin Lymphoma

2014 ◽  
Vol 20 (11) ◽  
pp. 1864-1868 ◽  
Author(s):  
Robert Chen ◽  
Joycelynne M. Palmer ◽  
Ni-Chun Tsai ◽  
Sandra H. Thomas ◽  
Tanya Siddiqi ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Brentuximab Vedotin ◽  
Free Survival

Results of Alemtuzumab-Based Reduced-Intensity Allogeneic Transplantation for Advanced Chronic Lymphocytic Leukemia: A BSBMT Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2899-2899
Author(s):  
Julio Delgado ◽  
Kirsty Thomson ◽  
Nigel Russell ◽  
Joanne Ewing ◽  
Wendy Stewart ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Autologous Hct ◽  
Reduced Intensity ◽  
Related Mortality

Abstract We report 41 consecutive patients with advanced chronic lymphocytic leukemia (CLL) who underwent allogeneic hematopoietic cell transplantation (HCT) following fludarabine, melphalan and alemtuzumab reduced intensity conditioning. Donors were 24 HLA-matched siblings and 17 unrelated volunteers (4 of them mismatched). Median age at transplant was 54 (range 37–67) years, interval from diagnosis to HCT was 54 (10–164) months, and number of previous chemotherapy regimens was 3 (1–6). Eleven patients were refractory to fludarabine at the time of transplant and 3 others (8%) had it stopped due to immune cytopenias. Eleven patients had failed autologous HCT. At the time of transplant, 7 patients (17%) had chemo-refractory and 34 (83%) chemo-sensitive disease, but only 5 (12%) were in complete remission. All but 3 patients had initial hematological recovery, but 5 more patients had delayed graft failure that responded to subsequent stem-cell infusions. Median intervals to neutrophil (> 0.5 × 109/l) and platelet (> 20 × 109/l) recovery were 14 (range 9–30) and 11 (range 8–45) days, respectively. Eleven patients (27%) relapsed and received escalated donor lymphocyte infusions, but only 3 of them had a sustained response. Acute and chronic graft-versus-host disease (GVHD) was observed in 17 (41%) and 13 (33%) patients, respectively. With a median follow-up of 15 (range 0.2–62) months, 17 patients have died, 5 of progressive disease and 12 of transplant-related complications. The 2-year overall survival, progression-free survival and transplant-related mortality are 51% (CI 33%–69%), 45% (27%–62%) and 26% (14%–46%), respectively (Figure 1). In multivariate analysis, fludarabine refractoriness prior to transplant was the only factor to predict a worse progression-free survival in this setting. In conclusion, the alemtuzumab-based regimen was feasible and effective in patients with CLL with a relatively low rate of GVHD. However, transplant-related mortality remains relatively high as a result of a variety of viral and fungal infections. Ongoing studies are aiming to address the efficacy of reduced doses of alemtuzumab in this group of very immunosupressed patients. Figure Figure

scholarly journals Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 3865-3871 ◽  
Author(s):  
Emma Morris ◽  
Kirsty Thomson ◽  
Charles Craddock ◽  
Prem Mahendra ◽  
Donald Milligan ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Donor Lymphocyte Infusion ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Peripheral Blood Stem Cells ◽  
Non Hodgkin Lymphoma ◽  
Reduced Intensity

Abstract We report the outcomes after reduced-intensity conditioning allogeneic stem cell transplantation (RIT) for non-Hodgkin lymphoma (NHL) in 88 patients (low-grade NHL [LG-NHL], n = 41; high-grade NHL [HG-NHL], n = 37; mantle cell lymphoma [MCL], n = 10). Thirty-seven patients had previously received autografts, and 21 were in complete remission (CR) at transplantation. Conditioning therapy consisted of alemtuzumab, fludarabine, and melphalan. Sixty-five patients received peripheral blood stem cells (PBSCs) from HLA-identical siblings, and 23 received bone marrow (BM) from matched unrelated donors. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporin A. Grade III-IV acute GVHD developed in 4 patients, and chronic GVHD developed in 6 patients. With a median follow-up of 36 months (range, 18-60 months), the actuarial overall survival (OS) rates at 3 years were 34% for HG-NHL, 60% for MCL, and 73% for LG-NHL (P < .001). The 100-day and 3-year transplant-related mortality (TRM) rates for patients with LG-NHL were 2% and 11%, respectively, and were better (P = .01) than they were for patients with HG-NHL (27% and 38%, respectively). The actuarial current progression-free survival (PFS) rate at 3 years, including the rate for patients who achieved remission after donor lymphocyte infusion (DLI) for progression, was 65% for LG-NHL, 50% for MCL, and 34% for HG-NHL (P = .002). Twenty-one patients underwent DLI for matched related donor (MD)-persistent disease or relapse, and 15 underwent DLI for mixed hematopoietic chimerism. Patients who experienced relapses of LG-NHL and chronic lymphocytic leukemia (CLL) achieved excellent PFS with extremely low TRM and GVHD, even when matched related donors were unavailable. (Blood. 2004;104:3865-3871)

Single Center Retrospective Comparison of Gvhd Preventive Regimens after Cy/Flu Minimal Intensity Allotransplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5874-5874
Author(s):  
Praveen Ranganath ◽  
Michael J. Robertson ◽  
Rafat Abonour ◽  
Jennifer E. Schwartz ◽  
Sherif Farag ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Single Agent ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Peripheral Blood Mononuclear ◽  
Minimal Intensity

Abstract Graft-versus-host disease (GVHD) remains the 2nd leading cause of mortality—after relapse/progression following allogeneic hematopoietic cell transplantation for the treatment of hematological malignancies. The incidence of clinically significant GVHD ranges from 10 to 80% and accounts for approximately 10-20% transplant related mortality. The combination calcineurin inhibitor and methotrexate is widely used as a GVHD preventive following myeloablative conditioning; however, there is no standard prophylaxis regimen for Cy/Flu minimal intensity nonablative transplants. The objective of the current study is to compare outcomes in patients treated at a single institution with identical conditioning regimens and supportive methods but different GVHD preventive regimens. Outcomes on 134 patients who underwent nonmyeloablative transplant between May 2000 and Nov 2011 were retrospectively analyzed. The primary endpoint was incidence and severity of acute GVHD (aGVHD). Secondary endpoints included incidence and severity of chronic GVHD (cGVHD), incidence of relapse, overall survival (OS), progression-free survival (PFS) and causes of death. Median follow-up was 49 months; the median age at transplant was 56 years, 66% of patient were not in remission at time of transplant (predominately myelodysplasia). Donors were peripheral blood mononuclear cell (PBMC, n=133) or bone marrow (n=1) HLA matched related or partially matched (9/10) donors. GVHD preventive regimens included the following: (1) single agent cyclosporine (CsA); (2) combination CsA/mycophenolate mofetil (MMF); (3) CsA+ basiliximab after ANC > 500/mm3; (4) CsA + basiliximab post-transplant, pre-engraftment; (5) sirolimus + tacrolimus. The incidence of grade III-IV acute GVHD was lower in patients who received sirolimus/tacrolimus than patients in the cyclosporine group (25% and 32%, respectively; p = .062). There was a significantly higher proportion of patients in the cyclosporine group who had clinical extensive chronic GVHD (62% vs. 25%, p = .008). The incidence of relapse trended higher in the sirolimus/tacrolimus group compared to CsA alone or CsA/MMF (50% vs. 28% vs. 30%, respectively, p= .519). There was a trend towards slightly better OS and PFS with the cyclosporine-based prophylaxis, but follow-up was longer with these regimens. Sirolimus/tacrolimus provides potent GVHD prophylaxis for nonmyeloablative Cy/Flu allogeneic transplantation; however, may be associated with higher relapse/progression rates. Larger numbers and/or comprehensive analyses of multicenter registry data might help further delineate differences in clinical outcomes between these regimens. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcome of Hodgkin Lymphoma after Progression Following Autologous Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2994-2994
Author(s):  
Joseph M. Connors ◽  
Alina S Gerrie ◽  
Maryse M Power ◽  
Kerry J Savage
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Single Agent ◽  
Progression Free Survival ◽  
Brentuximab Vedotin ◽  
Primary Objective ◽  
Initial Diagnosis ◽  
Cell Transplant ◽  
Free Survival

Abstract Background Clinical trials have demonstrated a high level of effectiveness for brentuximab vedotin (BV) for patients with relapsed or refractory classical Hodgkin lymphoma (HL); however, how patients fare in routine clinical practice if their HL recurs after autologous stem cell transplant (ASCT) is less clear. Our primary objective was to characterize overall survival (OS) and progression-free survival (PFS) among a cohort of real-world patients treated with BV after ASCT. The secondary objective was to characterize the outcome of treatment after failure of ASCT or ASCT and BV. Methods We screened the population-based British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database to identify patients with classical HL (excluding lymphocyte predominant HL) who were aged >16 years at initial diagnosis, staged and treated in BC, had primary treatment with ABVD or equivalent chemotherapy, underwent ASCT as part of first treatment for refractory or relapsed disease and relapsed again after ASCT. We excluded patients who have been treated at any time with a checkpoint inhibitor. We determined Kaplan-Meier estimates of overall (OS) and progression free survival (PFS) from the date of the progression that occurred after ASCT and, for those treated with the agent, after subsequent BV. Therapies given in sequence without a pause between therapies were considered part of the same line of therapy. Results Between 1986 and 2015 93 patients experienced recurrence of HL after ASCT. Their median age at initial diagnosis was 30 years and 51% were male. After failure of ASCT 23 (25%) received radiation monotherapy and 61 received chemotherapy (66%), either as a single agent or in various combinations and of these 9 (10%) also received radiation; 6 (6%) received a second transplant (5 allogeneic and 1 repeat ASCT); and 5 refused or were too frail for treatment other than with corticosteroids. The median PFS and OS from the time of relapse after ASCT for these 93 patients were 7.1 (range 0.2-352) and 16.2 months (range 0.2-352), respectively. Of those 93, 17 patients received BV alone or BV+bendamustine at some point following ASCT. The median age of BV-treated patients was 33 years at the time of their original diagnosis and 29% were male. Among those 17 patients, 9 received single agent BV and 8, BV+bendamustine as part of a clinical trial. The median time from ASCT to the start of BV was 27.5 months. Counting ASCT as 2nd line treatment, 10 individuals received BV as 3rd line, 6 as 4th line and 1 as 5th line therapy. For all 17 patients the subsequent median PFS and OS from the time of BV initiation were 5.1 (range 1.5-34.6) and 18.8 months (range 2.4-40.5), respectively. 12 of these patients relapsed again and their subsequent median PFS and OS were 0.6 (range 0.5-29) and 3 (range 0.5-30) months, respectively. All 9 patients who received single agent BV relapsed again at a median of 2 months (range 1.2-9.7); 5 of the 8 patients treated with BV+bendamustine remain in remission 6 to 36 months later. Conclusions These data highlight the poor prognosis for patients with relapsed or refractory cHL, particularly for those whose lymphoma recurs after brentuximab vedotin as well as the highly individualized management of patients whose lymphoma has recurred after ASCT. Future therapies that prevent or significantly delay relapse will help in alleviate the substantial clinical burden due to relapsed and refractory Hodgkin lymphoma. Disclosures Connors: Millennium Takeda: Research Funding; Seattle Genetics: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Bristol Myers Squib: Research Funding.

Allogeneic Stem-Cell Transplantation Using a Reduced-Intensity Conditioning Regimen Has the Capacity to Produce Durable Remissions and Long-Term Disease-Free Survival in Patients With High-Risk Acute Myeloid Leukemia and Myelodysplasia

2005 ◽  
Vol 23 (36) ◽  
pp. 9387-9393 ◽  
Author(s):  
Sudhir Tauro ◽  
Charles Craddock ◽  
Karl Peggs ◽  
Gulnaz Begum ◽  
Premini Mahendra ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Purpose The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural. Patients and Methods Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years). Results The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation. Conclusion The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning.

Favorable Long-Term Survival After Reduced-Intensity Allogeneic Transplantation for Multiple-Relapse Aggressive Non-Hodgkin's Lymphoma

2009 ◽  
Vol 27 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Kirsty J. Thomson ◽  
Emma C. Morris ◽  
Adrian Bloor ◽  
Gordon Cook ◽  
Don Milligan ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Allogeneic Transplantation ◽  
Published Data ◽  
Term Survival ◽  
Experienced Treatment ◽  
Reduced Intensity

Purpose The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, with relatively little published data. We report the outcome of reduced-intensity transplantation (RIT) in a cohort of 48 consecutive patients with relapsed/refractory DLBCL (30 patients with de novo disease and 18 patients with transformed follicular lymphoma) who underwent transplantation with an alemtuzumab-containing regimen, with a median follow-up of 52 months. Patients and Methods Patients had experienced treatment failure with a median of five lines of prior therapy, including autologous transplantation in 69%, and 17% of patients were chemotherapy refractory at transplantation. Median age was 46 years, and 38% of patients had matched/mismatched unrelated donors. Conditioning was with alemtuzumab, fludarabine, and melphalan, and additional graft-versus-host disease (GVHD) prophylaxis was with cyclosporine. Results All patients were successfully engrafted. Only 17% of patients developed grade 2 to 4 acute GVHD, with 13% experiencing extensive chronic GVHD. Four-year estimated nonrelapse mortality was 32%, and relapse risk was 33%. Twelve patients received donor lymphocyte infusions ± chemoimmunotherapy for relapse, and five patients obtained durable remissions, giving current progression-free survival (PFS) and overall survival (OS) rates at 4 years of 48% and 47%, respectively. Patients who had chemotherapy-sensitive disease before RIT had current PFS and OS rates at 4 years of 55% and 54%, respectively. Chemotherapy-refractory patients had a poor outcome. Conclusion The encouraging survival rates with extended follow-up suggest a role for RIT in chemotherapy-sensitive relapsed DLBCL, even in patients who have previously experienced treatment failure with autologous transplantation. Future studies will be required to determine whether any subset of patients with relapsed DLBCL should be considered for RIT versus autologous transplantation.

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