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The outcome of patients with Hodgkin lymphoma and early relapse after autologous stem cell transplant has improved in recent years
Bazarbachi, A., Boumendil, A., Finel, H., Khvedelidze, I., Romejko-Jarosinska, J., Tanase, A., Akhtar, S., Ben Othman, T., Ma'koseh, M., Afanasyev, B., et al
Leukemia. 2022
Abstract
Hodgkin lymphoma (HL) patients who relapse after autologous-stem-cell- transplantation (auto-SCT) have traditionally had a poor prognosis. We analyzed 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. The 4-year overall survival (OS) after relapse continuously increased from 32% for patients relapsing in 2006-2008, to 63% for patients relapsing in 2015-2017 (p = 0.001). The improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p = 0.01). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status, bulky disease, extranodal disease and presence of B symptoms at relapse were associated with a worse OS. Brentuximab vedotin (BV), checkpoint inhibitors (CPI) and second transplant (SCT2; 86% allogeneic) were used in 233, 91 and 330 patients respectively. The 4-year OS from BV, CPI, and SCT2 use was 55%, 48% and 55% respectively. In conclusion, the outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse. These large-scale real-world data can serve as benchmark for future studies in this setting.
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2.
Long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation as first transplant for high-risk Hodgkin lymphoma: a retrospective analysis from the Lymphoma Working Party-EBMT
Gutiérrez-García, G., Martínez, C., Boumendil, A., Finel, H., Malladi, R., Afanasyev, B., Tsoulkani, A., Wilson, K. M. O., Bloor, A., Nikoloudis, M., et al
British journal of haematology. 2021
Abstract
We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in?vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58?months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.
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3.
Changes in patients population and characteristics of hematopoietic stem cell transplantation for relapsed/refractory Hodgkin lymphoma: an analysis of the Lymphoma Working Party of the EBMT
Sureda, A., Genadieva Stavrik, S., Boumendil, A., Finel, H., Khvedelidze, I., Dietricht, S., Dreger, P., Hermine, O., Kyriakou, C., Robinson, S., et al
Bone marrow transplantation. 2020
Abstract
Indications for autologous (auto-HCT) and allogeneic transplantation (allo-HCT) in relapsed/refractory Hodgkin lymphoma (rrHL) have been long established. The expectation is that long-term outcomes have significantly improved over time with increased experience in these procedures. The objective of this study was to assess whether this is the case and to identify further areas of improvement. A total of 13,639 adult patients receiving an auto-HCT or allo-HCT for rrHL were reported to the European Society for Blood and Marrow Transplantation (EBMT) over a 25-year period. Regarding auto-HCT, recipients are younger, interval between diagnosis and transplant shorter, peripheral blood has become the universal stem cell source and the use of total body irradiation is almost non-existent in recent years. Allo-HCT is currently mostly used as a second transplant; recipients are younger, fitter and less frequently, chemorefractory. Reduced intensity conditioning protocols have vastly replaced myeloablative protocols. Increasing numbers of haplo-HCT have been reported. Both in auto-HCT and allo-HCT, NRM, PFS and OS have significantly improved but relapse remains the main cause of treatment failure. A better selection of patients and improvements in the supportive care has resulted in a reduction in the NRM. Relapse after HCT remains unchanged and further research is needed.
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4.
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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5.
Second autologous stem cell transplantation for relapsed/refractory Hodgkin lymphoma after a previous autograft: a study of the lymphoma working party of the EBMT
Martinez, C., Boumendil, A., Romejko-Jarosinska, J., Anagnostopoulos, A., Faber, E., Poire, X., Yakoub-Agha, I., Akhtar, S., Gurman, G., Pavone, V., et al
Leukemia & lymphoma. 2020;:1-8
Abstract
The purpose of this study was to analyze the results of second autologous hematopoietic stem cell transplantation (ASCT2) for patients with relapsed/refractory Hodgkin lymphoma (HL) after a first transplantation (ASCT1). Outcomes for 56 patients receiving an ASCT2 registered in the EBMT database were analyzed. The 4-year cumulative incidences of non-relapse mortality and disease relapse/progression were 5% and 67%, respectively. The 4-year overall survival (OS) and progression-free survival (PFS) were 62% and 28%. In univariate analysis, relapse of HL within 12 months of ASCT1 was associated with a worse OS (35% versus 76%, p = 0.01) and PFS (19% versus 29%, p = 0.059). Chemosensitivity at ASCT2 predicted better outcomes (4-year OS 72% versus 29%, p = 0.002; PFS 31% versus 12%, p = 0.015). This series shows that ASCT2 is a safe procedure and a relatively effective option for patients with late relapses after ASCT1 and with chemosensitive disease who are not eligible for an allogeneic transplant.
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6.
Outcomes of advanced Hodgkin lymphoma after umbilical cord blood transplantation: a Eurocord and EBMT Lymphoma and Cellular Therapy & Immunobiology Working Party study
Paviglianiti, A., Maio, K. T., Rocha, V., Gehlkopf, E., Milpied, N., Esquirol, A., Chevallier, P., Blaise, D., Gac, A. C., Leblond, V., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Allogeneic stem cell transplantation is an alternative for patients with relapsed or refractory Hodgkin lymphoma (HL) but only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 131 adults with HL who underwent UCBT in EBMT centers from 2003 to 2015. Disease status at UCBT was complete remission (CR) in 59 (47%) and almost all patients had received a previous autologous stem cell transplantation. The 4-year PFS and OS were 26% (95% CI 19-34%) and 46% (95% CI 37-55%), respectively. Relapse incidence was 44% (95% CI 36-54%) and non-relapse mortality (NRM) was 31% (95% CI 23-40%) at 4 years. In multivariate analysis, refractory/relapsed disease status at UCBT was associated with increased relapse incidence (HR=3.14 [95% CI 1.41-7.00], p=0.005) and NRM (HR=3.61 [95% CI 1.58-8.27], p=0.002), lower PFS (HR=3.45 [95% CI 1.95-6.10], p<0.001) and OS (HR=3.10 [95% CI 1.60-5.99], p=0.001). Conditioning regimen with cyclophospamide+fludarabine+2Gy total body irradiation (Cy+Flu+2 GyTBI) was associated with decreased risk of NRM (HR=0.26 [95% CI 0.10-0.64], p=0.004). Moreover, Cy+Flu+2 GyTBI conditioning regimen was associated with a better OS (HR=0.25 [95% CI 0.12-0.50], p<0.001) and PFS (HR=0.51 [95% CI 0.27-0.96], p=0.04). UCBT is feasible in heavily pretreated patients with HL. The reduced intensity conditioning regimen with Cy+flu+2 GyTBI is associated with a better OS and NRM. However, outcomes are poor in patients not in CR at UCBT.
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7.
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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8.
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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9.
High dose chemotherapy and autologous stem cell transplantation in nodular lymphocyte-predominant Hodgkin lymphoma: A retrospective study by the European society for blood and marrow transplantation-lymphoma working party
Akhtar, S., Montoto, S., Boumendil, A., Finel, H., Masszi, T., Jindra, P., Nemet, D., Fuhrmann, S., Beguin, Y., Castagna, L., et al
American Journal of Hematology. 2017
Abstract
Whilst autologous stem cell transplantation (auto-SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto-SCT in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto-SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003 and 2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto-SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13-58), and the median number of prior treatment lines was 2 (range 1-5), including rituximab in 63% of the patients. At auto-SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. Seventy-two percent of the patients received BEAM as high-dose therapy. With a median follow-up of 56 months (range 3-105), 5-year progression-free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto-SCT (vs PR, P=.049) for OS. Auto-SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long-term survival independent of the time interval between diagnosis and transplant. Copyright © 2017 Wiley Periodicals, Inc.