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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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Favorable outcomes of allogeneic hematopoietic stem cell transplantation with fludarabine-bendamustine conditioning and posttransplantation cyclophosphamide in classical Hodgkin lymphoma
Beynarovich, A., Lepik, K., Mikhailova, N., Borzenkova, E., Volkov, N., Moiseev, I., Zalyalov, Y., Kondakova, E., Kozlov, A., Stelmakh, L., et al
International journal of hematology. 2022
Abstract
INTRODUCTION Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for patients with relapsed and refractory classic Hodgkin lymphoma (rrHL). However, the optimal conditioning regimen and GVHD prophylaxis for rrHL remain undetermined. The aim of this study was to investigate outcomes of allo-HSCT with a fludarabine plus bendamustine (FluBe) conditioning regimen and GVHD prophylaxis with posttransplantation cyclophosphamide (PTCY) in patients with rrHL. METHODS Allo-HSCT results in 58 adult patients with rrHL were analyzed retrospectively. RESULTS Three-year overall survival and event-free survival were 81% (95% CI 65-91) and 55% (95% CI 38-72), respectively. The cumulative incidence of relapse (CIR) at 3 years was 33% (95% CI 13-51). The cumulative incidence of aGVHD grade II-IV and severe aGVHD grade III-IV was 36% (95% CI 22-48) and 22% (95% CI 9-33), respectively. The cumulative incidence of cGVHD was 32% (95% CI 17-45), including moderate or severe cGVHD in 17% (95% CI 4-28). Patients who developed aGVHD after allo-HSCT had significantly lower CIR (24% vs 49%, p = 0.004). The use of PBSC as a graft source also significantly reduced CIR (4% vs 61%, p = 0.002). CONCLUSIONS FluBe-PTCY allo-HSCT facilitates favorable outcomes, low toxicity, and mortality in rrHL.
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No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease
Thiel, U., Schober, S. J., Ranft, A., Gassmann, H., Jabar, S., Gall, K., von Lüttichau, I., Wawer, A., Koscielniak, E., Diaz, M. A., et al
Bone marrow transplantation. 2021
Abstract
Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n?=?39) versus HLA-matched grafts (group B, n?=?27). Median age at diagnosis was 13 years, and 15 years (range 3-49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p?0.02).
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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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Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT
Sanz, J., Galimard, J. E., Labopin, M., Afanasyev, B., Sergeevich, M. I., Angelucci, E., Kröger, N., Koc, Y., Ciceri, F., Diez-Martin, J. L., et al
Journal of hematology & oncology. 2021;14(1):84
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Editor's Choice
Abstract
BACKGROUND There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). METHODS We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n?=?78), matched unrelated (MUD) (n?=?94) and haploidentical family (Haplo) (n?=?297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. RESULTS Median age of patients was 38 years (range 18-76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p?=?0.4); 13%, 15%, and 15% (p?=?0.8); 35%, 50%, and 42% (p?=?0.01); and 11%, 17%, and 21% (p?=?0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p?=?0.8); and 21%, 18%, and 21% (p?=?0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p?=?0.8); 66%, 69%, and 62% (p?=?0.8); and 46%, 44%, and 35% (p?=?0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. CONCLUSIONS Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia (ALL) receiving allogeneic transplant in CR1 with prophylaxis with post-transplant cyclophosphamide (PTCy) prophylaxis (n=469)
Intervention
Haploidentical transplantation (n=297)
Comparison
Matched unrelated donor (MUD, n=94); matched sibling donor (MSD, n=78)
Outcome
Median age of patients was 38 years (range 18-76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34%; 13%, 15%, and 15%; 35%, 50%, and 42%; and 11%, 17%, and 21%, respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% and 21%, 18%, and 21% for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51%; 66%, 69%, and 62%; and 46%, 44%, and 35%, respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better leukaemia free survival.
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Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia
Nagler, A., Kanate, A. S., Labopin, M., Ciceri, F., Angelucci, E., Koc, Y., Gulbas, Z., Arcese, W., Tischer, J., Pioltelli, P., et al
Haematologica. 2020
Abstract
Graft-versus-host disease (GVHD) prophylaxis for unmanipulated haploidentical hematopoietic cell transplantation (haplo-HCT) include post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG). Utilizing EBMT registry, we compared ATG versus PTCy based GVHD prophylaxis in adult acute lymphoblastic leukemia (ALL) patients undergoing haplo-HCT. Included were 434 patients; ATG (n=98) and PTCy (n=336). Median follow-up was ~2 years. Baseline characteristics were similar between the groups except that the ATG-group was more likely to have relapsed/refractory ALL (P=0.008), non-TBI conditioning (P<0.001), peripheral blood graft source (P=<0.001) and transplanted at an earlier time-period (median year of HCT 2011 vs. 2015). The 100-day grade II-IV and III-IV acute-GVHD was similar between ATG and PTCy, as was 2-year chronic-GVHD. On multivariate analysis (MVA), leukemia-free survival (LFS) and overall survival (OS) was better with PTCy compared to ATG prophylaxis. Relapse incidence (RI) was lower in the PTCy group (P=0.03), while non-relapse mortality (NRM) was not different. Advanced disease and lower performance score were associated with poorer LFS and OS and advanced disease with inferior GVHD-free/relapse-free survival (GRFS). Peripheral grafts were associated with higher GVHD compared to bone marrow grafts. In ALL patients undergoing unmanipulated haplo-HCT, PTCy for GVHD prevention resulted in lower RI and improved LFS and OS compared to ATG.
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Comparison of Haploidentical Bone Marrow versus Matched Unrelated Donor Peripheral Blood Stem Cell Transplantation with Post-transplant Cyclophosphamide in Patients with Acute Leukemia
Nagler, A., Labopin, M., Dholaria, B., Angelucci, E., Afanasyev, B., Cornelissen, J. J., Sica, S., Meijer, E., Ciceri, F., Van Gorkom, G., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020
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Editor's Choice
Abstract
BACKGROUND Post-transplant cyclophosphamide (PTCy) is increasingly being utilized as a principle graft-versus-host disease (GvHD) prophylaxis strategy in allogeneic hematopoietic cell transplantation (allo-HCT). A haploidentical (haplo) or matched unrelated donor (UD) are valid options in the absence of a matched related donor. EXPERIMENTAL DESIGN We compared the outcomes of patients with acute leukemia who underwent haplo bone marrow (haplo-BM, N=401) versus UD mobilized peripheral blood stem cells (UD-PB, N=192) transplantation in the setting of PTCy. RESULTS The median follow-up duration was 36 months in the haplo-BM group and 16.6 months in the UD-PB group, respectively (p<0.01). Myeloablative conditioning was used in 64.6% and 42.7% of haplo-BM and UD-PB patients, respectively (p<0.01). Cumulative incidence of neutrophil engraftment at day 30 was 87% in haplo-BM versus 94% in UD-PB, respectively (p =0.21). In the multivariate analysis, the risk of grade II-IV acute GvHD (HR=0.53, p=0.01) and chronic GvHD (HR=0.50, p=0.02) was significantly lower in the haplo-BM group compared to the UD-PB group. There was no significant difference between the study groups, with respect to relapse incidence, non-relapse mortality, leukemia-fee survival, overall survival or, GvHD-free, relapse-free survival. CONCLUSION The use of a haplo donor with a BM graft resulted in a lower incidence of GvHD compared to a UD-PB stem cell graft in the setting of PTCy for patients with acute leukemia. However, differences in GvHD did not translate into the difference in survival outcomes. Based upon these data, UD-PB or haplo-BM should be considered equally acceptable sources for allo-HCT.
PICO Summary
Population
Patients with acute leukaemia (n=593)
Intervention
Haploidentical bone marrow transplantation with post-transplant cyclophosphamide (PTCy) (haplo-BM, n=401)
Comparison
Matched unrelated donor transplantation with mobilised peripheral blood stem cells (UD-PB, n=192)
Outcome
The median follow-up duration was 36 months in the haplo-BM group and 16.6 months in the UD-PB group, respectively. Myeloablative conditioning was used in 64.6% and 42.7% of haplo-BM and UD-PB patients, respectively. Cumulative incidence of neutrophil engraftment at day 30 was 87% in haplo-BM versus 94% in UD-PB, respectively. In the multivariate analysis, the risk of grade II-IV acute GvHD and chronic GvHD was significantly lower in the haplo-BM group compared to the UD-PB group. There was no significant difference between the study groups, with respect to relapse incidence, non-relapse mortality, leukemia-fee survival, overall survival or, GvHD-free, relapse-free survival.
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Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., et al
Bone marrow transplantation. 2020
Abstract
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
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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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Outcome of Patients with Fanconi Anemia developing myelodysplasia and acute leukemia who received Allogeneic Hematopoietic Stem Cell Transplantation: A retrospective analysis on Behalf of EBMT group
Giardino, S., Peffault de Latour, R., Aljurf, M., Eikema, D. J., Bosman, P., Bertrand, Y., Tbakhi, A., Holter, W., Bornhauser, M., Rossig, C., et al
American journal of hematology. 2020
Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured. This article is protected by copyright. All rights reserved.