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1.
Outcome of Allogeneic Transplantation for Mature T-cell Lymphomas: Impact of Donor Source and Disease Characteristics
Hamadani, M., Ngoya, M., Sureda, A., Bashir, Q., Litovich, C. A., Finel, H., Chen, Y., Boumendil, A., Zain, J., Castagna, L., et al
Blood advances. 2021
Abstract
Mature T-cell lymphomas constitute the most common indication of allogeneic hematopoietic cell transplantation (allo-HCT) in lymphomas. Large studies evaluating contemporary outcomes of allo-HCT in mature T-cell lymphomas, relative to commonly used donor sources are not available. Included in this registry study were adult patients who had undergone allo-HCT for anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma-NOS (PTCL-NOS) between 2008 and 2018. HCT platforms compared were post-transplant cyclophosphamide-based haploidentical (haplo-) HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in-vivo T-cell depletion (MUD TCD+), and MUD HCT without TCD (MUD TCD-). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included non-relapse mortality (NRM), and relapse/progression incidence (RI). 1942 patients were eligible (haplo-HCT 237; MSD 911; MUD-TCD+ 468; MUD TCD- 326). Cohorts were comparable for baseline characteristics except higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. On univariate and multivariate comparisons, OS and PFS, RI, and NRM were not significantly different between haplo-HCT, MSD, MUD-TCD+, and MUD-TCD- cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%; and 50%, 50%, 48%, and 52%, respectively. Significant predictors of inferior OS and PFS on multivariate analysis were active disease status at HCT and decreased PS. AITL was associated with significantly reduced relapse risk and better PFS compared to PTCL-NOS. Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma. Outcomes of haplo-HCT were comparable to that of matched donor allo-HCT.
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2.
Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma
Merryman, R. W., Castagna, L., Giordano, L., Ho, V. T., Corradini, P., Guidetti, A., Casadei, B., Bond, D. A., Jaglowski, S., Spinner, M. A., et al
Leukemia. 2021
Abstract
Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.
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3.
Tandem autologous-reduced intensity allogeneic stem cell transplantation in high-risk relapsed Hodgkin lymphoma: a retrospective study of the Lymphoma Working Party-EBMT
Bento, L., Boumendil, A., Finel, H., Khvedelidze, I., Blaise, D., Fegueux, N., Castagna, L., Forcade, E., Chevallier, P., Mordini, N., et al
Bone marrow transplantation. 2020
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Full text
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Editor's Choice
Abstract
Autologous hematopoietic stem cell transplantation (ASCT) is curative for a proportion of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). However, there is a small group of patients with high-risk of relapse after ASCT that might benefit from other approaches. We conducted a retrospective analysis on 126 patients treated with tandem ASCT-reduced intensity conditioning (RIC)-allogeneic-SCT and reported to the EBMT registry to analyze the efficacy and safety of this approach. Patients were included if they had received an ASCT followed by a planned RIC-SCT in <6 months without relapse between the procedures. The median time between diagnosis and ASCT was 16 months (2-174). The median number of lines prior to ASCT was two (33% of the patients received >3 lines). Forty-one percent were transplanted with active disease. The median follow-up was 44 months (6-130). Three-year-progression-free survival (PFS), overall survival (OS), incidence of relapse (IR), and non-relapse mortality (NRM) after the tandem were 53% (45-64), 73% (65-81), 34% (24-42), and 13% (8-21), respectively. This is the largest series analyzing the efficacy and safety of a tandem approach in R/R HL. The low NRM and IR with promising PFS and OS suggest that this might be an effective procedure for a high-risk population.
PICO Summary
Population
Patients with high-risk Hodgkin lymphoma (n=126)
Intervention
Tandem procedure of autologous stem cell transplant (ASCT) followed by a planned allogeneic transplant with reduced intensity conditioning (RIC-SCT), in <6 months without relapse between the procedures
Comparison
None
Outcome
The median time between diagnosis and ASCT was 16 months (2-174). The median number of lines prior to ASCT was two (33% of the patients received >3 lines). Forty-one percent were transplanted with active disease. The median follow-up was 44 months (6-130). Three-year-progression-free survival (PFS), overall survival (OS), incidence of relapse (IR), and non-relapse mortality (NRM) after the tandem were 53% (45-64), 73% (65-81), 34% (24-42), and 13% (8-21), respectively.
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4.
Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: EBMT Registry Analyses Following Allogeneic Stem Cell Transplantation for B-Cell Malignancies
Tomaszewska, A., Jagasia, M., Beohou, E., van der Werf, S., Blaise, D., Kanfer, E., Milpied, N., Reményi, P., Ciceri, F., Bourhis, J. H., et al
Frontiers in immunology. 2020;11:613954
Abstract
Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001-2013) with either rituximab (R-RIC-9%) or non-rituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1-77.3) and 43.2 months (range 0.3-179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study.
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5.
Refractory and 17p-deleted chronic lymphocytic leukemia: improving survival with pathway inhibitors and allogeneic stem cell transplantation
Farina, L., Barretta, F., Scarfo, L., Bruno, B., Patriarca, F., Frustaci, A. M., Coscia, M., Salvetti, C., Quaresmini, G., Fanin, R., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of high-risk CLL treated with alloSCT or B-cell receptor pathway inhibitors (BCRis) or both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced intensity alloSCT, and 19 received alloSCT with BCRis before and/or after transplant. An inverse probability of treatment weighting analyses were performed to compare alloSCT versus no-alloSCT groups: 5-year OS, PFS, and cumulative incidence of NRM and relapse were 40%/60% (p=0.096), 34%/17% (p=0.638), 28%/5% (p=0.016), and 38%/83% (p=0.005), respectively. Patients treated with alloSCT+BCRis showed a 3-year OS of 83%. Three -year OS and NRM by year of alloSCT, including patients treated with BCRis, were 53% and 17% in 2000-2007, 55% and 30% in 2008-2012 and 72% and 18% in 2013-2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients.
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6.
Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia
Michallet, M., Dreger, P., Sobh, M., Koster, L., Hoek, J., Boumendil, A., Scheid, C., Fox, C. P., Wulf, G., Kruger, W., et al
Bone marrow transplantation. 2019
Abstract
The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.
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7.
Allogeneic transplantation for relapsed and refractory Hodgkin lymphoma: long-term outcomes and graft-versus-host disease-free/relapse-free survival
Spina, F., Radice, T., De Philippis, C., Soldarini, M., Di Chio, M. C., Dodero, A., Guidetti, A., Viviani, S., Corradini, P.
Leukemia & lymphoma. 2018;:1-9
Abstract
This monocentric retrospective study included 70 consecutive relapsed/refractory Hodgkin lymphoma (RR-HL) patients receiving reduced-intensity allogeneic stem cell transplantation (alloSCT). We evaluated overall and progression-free survival (OS, PFS), graft-versus host disease/relapse-free survival (GFRS), and chronic GVHD-free OS (cGVHD-free OS) defined as OS without moderate-to-severe cGVHD. Patients had a median age of 33 years (range, 18-60 years), 23% had refractory disease (SD/PD). Donors were HLA identical (39%), unrelated (30%), or haploidentical (31%). Median follow-up was 6.2 years. Five-year OS was 59% and PFS was 49%. NRM was 16% at 1 year. 44% of patients had cGVHD, and 14% moderate-to-severe cGVHD at last follow-up. GFRS and cGVHD-free OS were 26 and 48% at 5 years. In multivariate analysis, resistant disease at alloSCT impacted survival and GFRS. In conclusion, disease response before alloSCT impacts survival and GFRS. GVHD outcomes may help comparing the long-term effects of the new salvage treatments that bridge patients to alloSCT.
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8.
Brentuximab vedotin for recurrent Hodgkin lymphoma after allogeneic hematopoietic stem cell transplantation: A report from the EBMT Lymphoma Working Party
Bazarbachi, A., Boumendil, A., Finel, H., Mohty, M., Castagna, L., Blaise, D., Peggs, K. S., Afanasyev, B., Diez-Martin, J. L., Corradini, P., et al
Cancer. 2018
Abstract
BACKGROUND The treatment of patients with Hodgkin lymphoma (HL) who develop disease progression after undergoing allogeneic stem cell transplantation (allo-SCT) remains challenging. METHODS The authors assessed outcomes in 184 adult patients with HL who developed disease recurrence or progression after a matched related or unrelated allo-SCT at European Society for Blood and Marrow Transplantation-participating centers between 2010 and 2014. RESULTS Eighty patients who received brentuximab vedotin (BV) salvage therapy were compared with 104 patients who did not. Patients in the BV group were younger (median age of 30 years vs 34 years) and were more likely to receive pretransplant BV (65% vs 46%) or posttransplant donor lymphocyte infusion (66% vs 33%). The 2 groups otherwise were comparable. Patients in the BV group received a median of 6 doses of posttransplant BV, resulting in a complete remission rate of 29%, a partial response rate of 45%, and a stable disease rate of 26%. Response to BV after allo-SCT did not appear to be affected by receipt of pretransplant BV. Despite a longer median follow-up for surviving patients in the BV group (33 months vs 23 months; P<.001), approximately 34% of the original BV cohort were alive and in CR at the time of last follow-up versus 18% in the group that did not receive BV (P=.003). The use of BV before donor lymphocyte infusion was found to be associated with the highest probability of being alive and in CR (40%) at the time of last follow-up. Salvage BV appeared to have no effect on chronic graft-versus-host disease or 1-year overall survival from the time of disease recurrence after allo-SCT (76% vs 67%). CONCLUSIONS BV is a safe and effective salvage therapy for patients with HL who develop disease recurrence or progression after undergoing allo-SCT, even after prior exposure to BV.
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9.
Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party
Bazarbachi, A., Boumendil, A., Finel, H., Mohty, M., Castagna, L., Peggs, K. S., Blaise, D., Afanasyev, B., Diez-Martin, J. L., Sierra, J., et al
British journal of haematology. 2018
Abstract
Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre-transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow-up for survivors was 41 months. Patients in the BV group were more heavily pre-treated (median pre-allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre-allograft BV had no impact on acute graft-versus-host disease (GVHD), non-relapse mortality, cumulative incidence of relapse, progression-free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0.64; 95% confidence interval = 0.45-0.92; P < 0.02). Older age, poor performance status, use of pre-transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success.
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10.
Real-life feasibility of salvage allogeneic transplantation in peripheral T-cell lymphomas
Mussetti, A., Martinetti, N., Cieri, N., Pennisi, M., Dodero, A., Corradini, P.
Bone marrow transplantation. 2018
Abstract
Relapsed/refractory Peripheral T-cell Lymphomas are characterized by a poor prognosis, especially for patients who are not candidates for allogeneic hematopoietic stem-cell transplantation. We conducted a retrospective analysis on 73 consecutive patients affected by relapsed/refractory T-Cell lymphomas who were considered eligible for allogeneic transplant. All patients were referred at our center from 2001 to 2017. With a median follow-up of 40 months (range 9-192 months), 4-year second-line failure-free survival and overall survival were 14% (CI95%:7-24) and 34% (CI95%:22-46). Extranodal disease at relapse (HR 2.25, CI95%: 1.11-4.56, p = 0.02) and first-line failure-free survival < 12 months (HR 3.37, CI95%: 1.67-6.88, p < 0.01) had a negative prognostic impact on survival. Only 45 out of 73 patients (62%) received allogeneic transplant. For the 28 (38%) patients who did not proceed to transplant, disease progression was the main reason for ineligibility. Median survival from time of transplant was 31 months (range 4-185 months). A first-line failure-free survival < 12 months had a negative prognostic impact also for allografted patients (2-year survival 45% vs 73%, p = 0.03) identifying a very high-risk population which requires novel treatments pre and post-transplant to obtain a long-term disease control.