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1.
Cord blood transplantation for AML: Comparable LFS in patients with de novo versus secondary AML in CR1, an ALWP/EBMT study
Baron, F., Nagler, A., Galimard, J. E., Sanz, J., Versluis, J., Forcade, E., Chevallier, P., Sirvent, A., Anthias, C., Kuball, J., et al
British journal of haematology. 2023
Abstract
We investigated whether secondary versus de novo acute myeloid leukaemia (AML) would be associated with poor outcomes in adult acute AML patients in first complete remission (CR1) receiving unrelated cord blood transplantation (CBT). This is a retrospective study from the acute leukaemia working party of the European Society for Blood and Marrow Transplantation. Inclusion criteria included adult at first allogeneic haematopoietic cell transplantation between 2000 and 2021, unrelated single or double unit CBT, AML in CR1, no ex vivo T-cell depletion and no post-transplant cyclophosphamide. The primary end-point of the study was leukaemia-free survival (LFS). A total of 879 patients with de novo (n = 696) or secondary (n = 183) AML met the inclusion criteria. In multivariable analyses, sAML patients had non-significantly different LFS (HR = 0.98, p = 0.86), overall survival (HR = 1.07, p = 0.58), relapse incidence (HR = 0.74, p = 0.09) and non-relapse mortality (HR = 1.26, p = 0.13) than those with de novo AML. Our results demonstrate non-significantly different LFS following CBT in adult patients with secondary versus de novo AML.
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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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3.
Retrospective analysis of hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: conditioning intensity matters
Bruch, P. M., Dietrich, S., Finel, H., Boumendil, A., Greinix, H., Heinicke, T., Bethge, W., Beelen, D., Schmid, C., Martin, H., et al
Leukemia. 2022
Abstract
Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare myeloid malignancy with a generally poor prognosis. Although preliminary evidence suggests that hematopoietic cell transplantation (HCT) could improve outcome in patients with BPDCN, the individual contributions of conditioning and graft-versus-tumor (GVT) effects to HCT success are undefined. We present a retrospective study of 162 adult patients who underwent a first HCT (allogeneic 146, autologous 16) between 2009 and 2017, and were registered with the EBMT. Median age was 57 (range 20-73) years, and disease status at HCT was first complete remission (CR1) in 78%. Among patients receiving allogeneic HCT (alloHCT), myeloablative conditioning (MAC), reduced intensity conditioning (RIC) and in-vivo T-cell depletion (TCD) were used in 54%, 46%, and 59% respectively. Total body irradiation (TBI) was the conditioning backbone in 61% of MAC and 26% of RIC transplants. One-year overall survival (OS) and progression-free survival (PFS) rates were comparable after alloHCT and autologous HCT (autoHCT). Among alloHCT recipients, MAC with TBI significantly improved OS and PFS, independently of CR1, age, Karnofsky index and TCD. Accordingly, MAC (ideally based on TBI) should be preferred for alloHCT recipients with BPDCN. In patients who are not elegible for MAC alloHCT, autoHCT could be considered.
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4.
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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5.
Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT
Gilleece, M. H., Shimoni, A., Labopin, M., Robinson, S., Beelen, D., Socié, G., Unal, A., Ganser, A., Vitek, A., Sengeloev, H., et al
Blood cancer journal. 2021;11(5):88
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Editor's Choice
Abstract
Measurable residual disease (MRD) prior to hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) in first complete morphological remission (CR1) is an independent predictor of outcome, but few studies address CR2. This analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry assessed HCT outcomes by declared MRD status in a cohort of 1042 adult patients with AML CR2 at HCT. Patients were transplanted 2006-2016 from human leukocyte antigen (HLA) matched siblings (n?=?719) or HLA 10/10 matched unrelated donors (n?=?293). Conditioning was myeloablative (n?=?610) or reduced-intensity (n?=?432) and 566 patients (54%) had in-vivo T cell depletion. At HCT, 749 patients (72%) were MRD negative (MRD NEG) and 293 (28%) were MRD positive (MRD POS). Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months (P?0.001). Two-year relapse rates were 24% (95% CI, 21-28) and 40% (95% CI, 34-46) in MRD NEG and MRD POS groups (P?0.001), respectively. Leukemia-free survival (LFS) was 57% (53-61) and 46% (40-52%), respectively (P?=?0.001), but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
PICO Summary
Population
Patients with AML who were transplanted in second complete remission (CR2) at transplant (n=1042)
Intervention
Patients who were minimal disease negative (MRD NEG, n=749)
Comparison
Patients who were minimal disease positive (MRD POS, n=293)
Outcome
Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months). Two-year relapse rates were 24% and 40% in MRD NEG and MRD POS groups, respectively. Leukemia-free survival (LFS) was 57% and 46%, respectively, but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
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6.
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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7.
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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8.
The conditional survival analysis of relapsed DLBCL after autologous transplant: a subgroup analysis of LY.12 and CORAL
Assouline, S., Li, S., Gisselbrecht, C., Fogarty, P., Hay, A., van den Neste, E., Shepherd, L. E., Schmitz, N., Baetz, T., Keating, A., et al
Blood advances. 2020;4(9):2011-2017
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Abstract
The conditional survival of patients after frontline therapy for diffuse large B-cell lymphoma (DLBCL) approaches that of the general population once patients have survived disease free for 2 years. We sought to determine the conditional survival of patients among patients with relapsed de novo DLBCL successfully undergoing an autologous stem-cell transplant (ASCT) after first relapse. A total of 478 patients with de novo DLBCL, relapsed after 1 treatment from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) and LY.12, were included. Patients were followed prospectively after ASCT for a median of 5.3 and 8.2 years, respectively. Individual patient data were analyzed for event-free survival (EFS) and overall survival. Standardized mortality ratios (SMRs) were estimated using French and Canadian life tables. The EFS estimates declined with each year of follow-up after ASCT and were 50.1% (95% confidence interval [CI]: 43.7% to 56.3%) and 43.4% (95% CI: 36.7% to 49.9%) at 5 years in CORAL and LY.12, respectively. The rate of death stabilized once patients achieved at least 4 years of EFS. Compared with the age- and sex-matched population, the SMR was significantly higher until 5 years after ASCT, when values were no longer statistically significant. Patients undergoing ASCT for relapsed DLBCL continue to have a higher rate of death at least until they have survived event free for 5 years. These observations can help to determine endpoints for future clinical trials in this population and for patient counseling. This trial was registered at www.clinicaltrials.gov as #NCT00078949.
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Impact of detectable measurable residual disease on umbilical cord blood transplantation
Baron, F., Labopin, M., Ruggeri, A., Sierra, J., Robinson, S., Labussiere-Wallet, H., Potter, M., Ribera, J. M., Deconinck, E., Rambaldi, A., et al
American journal of hematology. 2020
Abstract
The impact of measurable residual disease (MRD) on cord blood transplantation (CBT) outcomes has remained debated. To address this issue, we assessed the impact of measurable MRD at CBT on outcomes in large cohort of patients with acute leukemia. Inclusion criteria included adult patients with acute myeloid (AML) or acute lymphoblastic leukemia (ALL), CBT as first allo-HCT in first or second complete remission (CR) at transplantation, and known MRD status at the time of CBT. Data from 506 patients were included in the analysis. Among them, 317 patients had AML and 189 had ALL. Positive MRD was reported in 169 (33%) patients while the remaining 337 patients were MRD negative at CBT. At 2 years, relapse incidence was 18% in patients with MRD negativity versus 33% in those with MRD positivity at transplantation (P<0.001). Two-year leukemia-free survival (LFS) and overall survival (OS) were 57% and 60%, respectively, in MRD negative patients, versus 38% (P<0.001) and 48% (P=0.004), respectively, in those with MRD positivity. There was no interaction between the impact of MRD on OS and LFS and diagnosis (i.e. ALL versus AML), single or double CBT, and reduced-intensity or myeloablative conditioning. On multivariate analysis, MRD positivity was associated with a higher risk of relapse (HR=1.8, P=0.003), comparable non-relapse mortality (P=0.44), worse LFS (HR=1.4, P=0.008) and a trend towards worse OS (HR=1.3, P=0.065). In conclusion, these data suggest that novel strategies that are aiming to achieve MRD negativity at CBT are needed for leukemic patients with positive MRD pre-CBT. This article is protected by copyright. All rights reserved.
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10.
BEAM-Campath Allogeneic Stem Cell Transplant for Patients with Relapsed/Refractory Lymphoma: High Incidence of Long-Term Mixed Donor-Recipient Chimerism and the Response to Donor Lymphocyte Infusions
Burney, C., Wadhera, K., Breslin, P., Pearce, R., Wells, M., Alajangi, R., Protheroe, R., Marks, D. I., Griffin, J., Robinson, S.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020;26(12):2271-2278
Abstract
BiCNU (carmustine), etoposide, Ara-C, melphalan (BEAM) and Campath conditioning was developed to reduce the high transplant-related mortality in patients with lymphoma while delivering intensive antilymphoma immunotherapy, as well as to some extent a platform for allogeneic stem cell engraftment. Significant numbers of patients appeared to have persistent recipient-derived hematopoiesis, and therefore we retrospectively analyzed patients with lymphoma undergoing BEAM-Campath conditioned allogeneic stem cell transplantation at our center (2003 to 2017) to characterize the patterns of chimerism and patient outcomes. Chimerism was analyzed with short tandem repeat PCR. Mixed donor-recipient chimerism (MDRC) was defined as 5% to 94.9% donor. Fifty-two patients (n = 30 male), with a median age of 45 years, were identified with histologic diagnoses of Hodgkin lymphoma (n = 13), diffuse large B cell lymphoma (n = 7), low-grade non-Hodgkin lymphoma (n = 16), mantle cell lymphoma (n = 10), and T cell lymphoma (n = 6). Pretransplant, 93% achieved complete response (52%) or partial response (41%) with a median of 3 prior therapies (n = 3 prior autologous stem cell transplantation). Donors were Matched sibling donors (MSD) (n = 21), matched unrelated donors (MUD) (n = 24), miss-matched unrelated donors (MMUD) (n = 6), and syngeneic (n = 1). Acute graft-versus host disease (GVHD) developed in 52% (81% grade I to II) and chronic GVHD (83% extensive) in 12%. MDRC of T cells (MDRCt) developed in 62% (n = 32), and 29% (n = 15) developed MDRC of myeloid cells (MDRCm) at a median onset of 100 days. Donor lymphocyte infusion (DLI) was given to 17 patients, with a median starting dose of 1 × 10(6)/kg. The first DLI was given at a median of 225 days post-transplant (range, 99 days to 5.3 years). Of these, 9 developed acute post-DLI GVHD and 2 limited chronic GVHD. Conversion to full donor occurred in 47% MDRCt and 50% MDRCm. Multivariate analysis identified sibling donor type as associated with increased MDRCt (P = .035; hazard ratio [HR], 0.17) and reduced total nucleated cell dose with increased MDRCm (P = .021; HR, 0.76). The median follow-up was 6 years, and 2-year NRM cumulative incidence was 16% (95% confidence interval [CI], 7% to 27%). Ten-year progression and extensive GVHD-free survival was 45% (95% CI, 28% to 61%), and overall survival was 66% (95% CI, 50% to 78%). One-year landmark analysis identified no increased GVHD or relapse risk with MDRCt or MDRCm but reduced nonrelapse mortality (NRM) risk with MDRCt (P = .001). BEAM-Campath allografts for high-risk lymphoma achieve long-term disease-free survival with low rates of GVHD and transplant-related mortality. The frequent development of myeloid MDRC demonstrates that BEAM-Campath is a nonmyeloablative conditioning regimen in almost a third of patients. MDRCt is associated with reduced NRM, but neither MDRCt or MDRCm is associated with increased GVHD or relapse.