Continuously improving outcome over time after second allogeneic stem cell transplantation in relapsed acute myeloid leukemia: an EBMT registry analysis of 1540 patients.

Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT (alloSCT1). Long-term EBMT registry data were used to provide large scale, up-to-date outcome results and to identify factors for improved outcome. Among 1540 recipients of alloSCT2, increasing age, better disease control and performance status before alloSCT2, more use of alternative donors and higher conditioning intensity represented important trends over time. Between the first (2000-2004) and last (2015-2019) period, two-year overall and leukemia-free survival (OS/LFS) increased considerably (OS: 22.5-35%, LFS: 14.5-24.5%). Cumulative relapse incidence (RI) decreased from 64% to 50.7%, whereas graft-versus-host disease and non-relapse mortality (NRM) remained unchanged. In multivariable analysis, later period of alloSCT2 was associated with improved OS/LFS (HR = 0.47/0.53) and reduced RI (HR = 0.44). Beyond, remission duration, disease stage and patient performance score were factors for OS, LFS, RI, and NRM. Myeloablative conditioning for alloSCT2 decreased RI without increasing NRM, leading to improved OS/LFS. Haploidentical or unrelated donors and older age were associated with higher NRM and inferior OS. In summary, outcome after alloSCT2 has continuously improved over the last two decades despite increasing patient age. The identified factors provide clues for the optimized implementation of alloSCT2.

PTCy versus CNI-based GVHD prophylaxis in HLA-matched transplants for Hodgkin Lymphoma: a study of the LWP of the EBMT.

Studies comparing the efficacy of post-transplant cyclophosphamide (PTCy) to conventional calcineurin inhibitor (CNI)-based GVHD prophylaxis regimens in Hodgkin lymphoma (HL) patients are scarce. This study aimed to compare the outcomes of HL patients undergoing hematopoietic stem cell transplantation from HLA-matched donors who received GVHD prophylaxis with either PTCy or conventional CNI-based regimens, using data reported to the EBMT database between January 2015 and December 2022. Among the cohort, 270 recipients received conventional CNI-based prophylaxis and 176 received PTCy prophylaxis. Notably, PTCy prophylaxis was associated with delayed hematopoietic recovery, but also with a lower risk of chronic (25% versus 43%, p<0.001) and extensive chronic GVHD (13% versus 28% p=0.003) compared to the CNI-based cohort. The 2-year cumulative incidence of non-relapse mortality and relapse were 11% versus 17% (p=0.12), and 17% versus 30% (p=0.007) for PTCy and CNI-based, respectively. Moreover, the 2-year overall survival, progression-free survival and GVHD-free, relapse-free survival were all significantly better in the PTCy group compared with the CNI-based group: 85% versus 72% (p=0.005), 72% versus 53% (p<0.001), and 59% versus 31% (p<0.001), respectively. In multivariable analysis, PTCy was associated with a lower risk of chronic and extensive chronic GVHD, reduced relapse, and better OS, PFS, and GRFS compared to the CNI-based platform. Our findings suggest that PTCy as GVHD prophylaxis offers more favorable outcomes compared to conventional CNI-based prophylaxis in adult patients with HL undergoing HSCT from HLA-matched donors.

Graft-versus-host-disease prophylaxis with ATG or PTCY in patients with lymphoproliferative disorders undergoing reduced intensity conditioning regimen HCT from one antigen mismatched unrelated donor.

Post-transplant cyclophosphamide (PTCY) has been introduced as graft-versus-host disease (GvHD) prophylaxis in mismatched and matched unrelated hematopoietic cell transplant (HCT). However, data comparing outcomes of PTCY or ATG in patients undergoing a 1 antigen mismatched HCT for lymphoproliferative disease are limited. We compared PTCY versus ATG in adult patients with lymphoproliferative disease undergoing a first 9/10 MMUD HCT with a reduced intensity conditioning regimen from 2010 to 2021. Patients receiving PTCY were matched to patients receiving ATG according to: age, disease status at transplant, female to male matching, stem cell source and CMV serology. Grade II-IV acute GvHD at 100 day was 26% and 41% for the ATG and PTCY group, respectively (p = 0.08). Grade III-IV acute GvHD was not significantly different between the two groups. No differences were observed in relapse incidence, non-relapse mortality, progression-free survival, overall survival and GvHD-relapse-free survival at 1 year. The cumulative incidence of 1-year extensive chronic GvHD was 18% in the ATG and 5% in the PTCY group, respectively (p = 0.06). In patients with lymphoproliferative diseases undergoing 9/10 MMUD HCT, PTCY might be a safe option providing similar results to ATG prophylaxis. Due to the limited number of patients, prospective randomized trials are needed.

Hematopoietic stem cell transplantation for pediatric patients with non-anaplastic peripheral T-cell lymphoma. An EBMT pediatric diseases working party study.

Peripheral T-cell lymphomas (PTCL) other than anaplastic large-cell lymphoma are rare in children, and the role of hematopoietic stem cell transplantation (HSCT) has not been clarified yet. In a retrospective analysis of registry-data of the European Society for Blood and Marrow Transplantation we analyzed 55 patients aged < 18 years who received allogeneic (N = 46) or autologous (N = 9) HSCT for PTCL. Median age at HSCT was 13.9 years; 33 patients (60%) were in first remission, and 6 (19%) in progression at HSCT. Conditioning was myeloablative in 87% of the allogeneic HSCTs and in 27 (58.7%) based on total body irradiation. After allogeneic HSCT the 5-year overall- and progression-free survival was 58.9% (95% CI 42.7-71.9) and 52.6% (95% CI 36.8-66.1), respectively. 5-year relapse incidence was 27.6% (95% CI 15.1-41.6), the non-relapse mortality rate was 19.8% (95% CI 9.7-32.6). Five of the six patients with progression at HSCT died. Seven of nine patients after autologous HSCT were alive and disease-free at last follow-up. Our data suggest a role of allogeneic HSCT in consolidation-treatment of patients with high-risk disease, who reach at least partial remission after primary- or relapse-therapy, whereas patients with therapy-refractory or progressive disease prior to transplantation do not profit from HSCT.

Comparison of fludarabine/melphalan (FluMel) with fludarabine/melphalan/BCNU or thiotepa (FBM/FTM) in patients with AML in first complete remission undergoing allogeneic hematopoietic stem cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.

Conditioning protocols for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) are being developed continuously to improve their anti-leukemic efficacy and reduce their toxicity. In this study, we compared the conditioning protocol of fludarabine with melphalan 140 mg/m2 (FluMel) with conditioning protocols based on this same backbone but with an additional alkylating agent i.e., either fludarabine/BCNU (also known as carmustine)/melphalan (FBM), or fludarabine/thiotepa/melphalan (FTM) 110 mg/m2. We included 1272 adult patients (FluMel, n = 1002; FBM/FTM, n = 270) with acute myeloid leukemia (AML) with intermediate/poor cytogenetic risk in first complete remission (CR) from the registry of the EBMT Acute Leukemia Working Party. Despite patients in the FBM/FTM group were older (64.1 years vs. 59.8 years, p < 0.001) and had a worse Karnofsky performance score (KPS < 90, 33% vs. 24%, p = 0.003), they showed a better overall survival (OS) (2 y OS: 68.3% vs. 58.1%, p = 0.02) and less non-relapse mortality (NRM) (2 y NRM: 15.8% vs. 22.2%, p = 0.009) compared to patients treated with FluMel. No significant differences were observed in relapse incidence (RI) (2 y RI: 24.9% vs. 23.7%, p = 0.62). In conclusion, the addition of a second alkylating agent (BCNU/carmustine or thiotepa) to FluMel as FBM/FTM conditioning, improves OS in AML patients in first CR with intermediate/poor risk cytogenetics after allo-HCT.

Unrelated or haploidentical allogeneic hematopoietic cell transplantation in second complete remission for acute myeloid leukemia-Improved outcomes over time: A European Society for Blood and Marrow Transplantation Acute Leukemia Working Party study.

BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood. METHODS: This is a retrospective, registry-based European Society for Blood and Marrow Transplantation study that investigates changes in patient- and transplant-related characteristics and posttransplant outcomes over time. RESULTS: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18-78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p < .001), use of a haplo donor (from 4.6% to 26.4%; p < .001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p < .001). There was a significant decrease in total body irradiation and in vivo T-cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia-free survival (hazard ratio [HR], 0.79; p = .002) and overall survival (HR, 0.73; p < .001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p < .001) decreased over time. We also observed better graft-vs-host disease (GVHD) rates (acute GVHD II-IV: HR, 0.78; p = .03; GVHD-free, relapse-free survival: HR, 0.69; p < .001). CONCLUSIONS: Even in the absence of an MSD, outcomes of allo-HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD.

Allogeneic hematopoietic cell transplantation for patients with AML aged 70 years or older in first remission. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Accessibility to allogeneic hematopoietic cell transplantation (HCT) programs for older patients is growing constantly. We report on the clinical outcomes of a group of 701 adults aged ≥70 years, with acute myeloid leukemia (AML) in first complete remission (CR1), who received a first HCT, from HLA-matched sibling donors (MSD), 10/10 HLA-matched unrelated donors (UD), 9/10 HLA-mismatched unrelated donors (mUD) or haploidentical (Haplo) donors. The 2-year overall survival (OS) was 48.1%, leukemia-free survival (LFS) 45.3%, relapse incidence (RI) 25.2%, non-relapse mortality (NRM) 29.5% and GVHD-free, relapse-free survival (GRFS), 33.4%. Compared to MSD, patients transplanted from Haplo and UD presented lower RI (HR 0.46, 95% CI 0.25-0.8, p = 0.02 and HR 0.44, 95% CI: 0.28-0.69, p = 0.001, respectively); this translated into prolonged LFS for Haplo (HR 0.62, 95% CI: 0.39-0.99, p = 0.04). Patients transplanted from mUD exhibited the highest NRM incidence (HR 2.33, 95% CI: 1.26-4.31, p = 0.007). HCT in selected adult CR1 AML patients >70 years is feasible and could be associated with good clinical outcomes. Prospective clinical trials are warranted.

Allogeneic hematopoietic stem cell transplantation for NK/T-cell lymphoma: an international collaborative analysis.

Natural killer/T-cell lymphomas (NKTCL) represent rare and aggressive lymphoid malignancies. Patients (pts) with relapsed/refractory disease after Asparaginase (ASPA)-based chemotherapy have a dismal prognosis. To better define the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), we conducted a retrospective analysis of data shared with the European Society for Blood and Marrow Transplantation (EBMT) and cooperating Asian centers. We identified 135 pts who received allo-HSCT between 2010 and 2020. Median age was 43.4 years at allo-HSCT, 68.1% were male. Ninety-seven pts (71.9 %) were European, 38 pts (28.1%) Asian. High Prognostic Index for NKTCL (PINK) scores were reported for 44.4%; 76.3% had >1 treatment, 20.7% previous auto-HSCT, and 74.1% ASPA-containing regimens prior to allo-HSCT. Most (79.3%) pts were transplanted in CR/PR. With a median follow-up of 4.8 years, 3-year progression-free(PFS) and overall survival were 48.6% (95%-CI:39.5-57%) and 55.6% (95%-CI:46.5-63.8%). Non-relapse mortality at 1 year was 14.8% (95%-CI:9.3-21.5%) and 1-year relapse incidence 29.6% (95%-CI:21.9-37.6%). In multivariate analyses, shorter time interval (0-12 months) between diagnosis and allo-HSCT [HR = 2.12 (95%-CI:1.03-4.34); P = 0.04] and transplantation not in CR/PR [HR = 2.20 (95%-CI:0.98-4.95); P = 0.056] reduced PFS. Programmed cell death protein 1(PD-1/PD-L1) treatment before HSCT neither increased GVHD nor impacted survival. We demonstrate that allo-HSCT can achieve long-term survival in approximately half of pts allografted for NKTCL.

Trends in outcome of transplantation in patients with secondary acute myeloid leukemia: an analysis from the Acute Leukemia Working Party (ALWP) of the EBMT.

Trends in outcome of transplantation (HSCT) in secondary acute myeloid leukemia (sAML) are limited. We evaluated results of HSCT in 4224 patients with sAML in complete remission; 1337 were transplanted in 2000-2010 and 2887 in 2011-2020. Median age was 54 (range, 18-74) and 59 (range, 18-78) years, respectively (p < 0.0001). Donors were MSD in 65% vs. 37%, 10/10 UD in 27% vs. 50%, and 9/10 UD in 8% vs. 13%, respectively (p < 0.0001). Conditioning was myeloablative in 46% and 38%, respectively. Two-year non-relapse mortality (NRM) was lower in patients transplanted in 2011-2020 vs. those transplanted in 2000-2010, 18% vs. 21% (hazard ratio (HR) = 0.82, 95% CI: 0.68-0.9; p = 0.04) and modified GVHD-free, relapse-free survival (GRFS) (HR = 0.9, 95% CI: 0.81-0.99; p = 0.04) was better in patients transplanted in the 2011-2020 vs. those transplanted in 2000-2010. Two-year relapse incidence (RI) was similar between the 2 groups with 32% vs. 31%, (HR = 1.05, 95% CI: 0.9-1.22; p = 0.55). Likewise, leukemia-free survival (LFS) (HR = 0.95, 95% CI: 0.84-1.07; p = 0.38) and overall survival (OS) (HR = 0.93, 95% CI: 0.82-1.05; p = 0.26) were not significantly different between the two periods. In conclusion, Incidence of NRM has been significantly reduced and GRFS significantly increased in HSCT for sAML in the last 2 decades.

Longitudinal Outcome over Two Decades of Unrelated Allogeneic Stem Cell Transplantation for Relapsed/Refractory Acute Myeloid Leukemia: An ALWP/EBMT Analysis.

PURPOSE: We evaluated outcomes of unrelated transplantation for primary refractory/relapsed (ref/rel) acute myeloid leukemia (AML), comparing two cohorts according to the year of transplant, 2000-2009 and 2010-2019. PATIENTS AND METHODS: Multivariable analyses were performed using the Cox proportional-hazards regression model. RESULTS: 3,430 patients were included; 876 underwent a transplant between 2000-2009 and 2554 in 2010-2019. Median follow-up was 8.7 (95% CI, 7.8-9.4) and 3.4 (95% CI, 3.1-3.6) years (P < 0.001). Median age was 52 (18-77) and 56 (18-79) years (P > 0.0001); 45.5% and 55.5% had refractory AML while 54.5% and 44.5% had relapsed AML. Conditioning was myeloablative in 60% and 52%, respectively. Neutrophil recovery and day 100 incidence of acute and 2-year incidence of chronic graft-versus-host disease (GvHD) were similar between the two periods. Two-year relapse incidence was higher for patients undergoing transplant in the 2000-2009 period versus those undergoing transplant in 2010-2019: 50.2% versus 45.1% (HR, 0.85; 95% CI, 0.74-0.97; P = 0. 002). Leukemia-free survival; overall survival; and GvHD-free, relapse-free survival were lower for the 2000-2009 period: 26% versus 32.1% (HR, 0.87; 95% CI, 0.78-0.97; P = 0.01), 32.1% versus 38.1% (HR, 0.86; 95% CI, 0.77-0.96; P = 0.01), and 21.5% versus 25.3% (HR, 0.89; 95% CI, 0.81-0.99; P = 0.03), respectively. Two-year nonrelapse mortality was not significantly different (23.8% vs. 23.7%; HR, 0.91; 95% CI, 0.76-1.11; P = 0.34). CONCLUSIONS: Outcome of unrelated transplantation for patients with ref/rel AML has improved in the last two decades, rescuing about one third of the patients. See related commentary by Adrianzen-Herrera and Shastri, p. 4167.

Outcome of allogeneic transplantation for mature T-cell lymphomas: impact of donor source and disease characteristics.

Mature T-cell lymphomas constitute the most common indication for allogeneic hematopoietic cell transplantation (allo-HCT) of all 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 not otherwise specified (PTCL-NOS) between 2008 and 2018. Hematopoietic cell transplantation (HCT) platforms compared were posttransplant cyclophosphamide-based haploidentical (haplo-)HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in vivo T-cell depletion (MUD TCD+), and matched unrelated donor HCT without in vivo T-cell depletion (MUD TCD-). Coprimary end points were overall survival (OS) and progression-free survival (PFS); secondary end points included nonrelapse mortality (NRM), and relapse/progression incidence (RI). A total of 1942 patients were eligible (237 haplo-HCT; 911 MSD; 468 MUD TCD+; 326 MUD TCD-). Cohorts were comparable for baseline characteristics with the exception of higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. Using univariate and multivariate comparisons, OS, PFS, RI, and NRM were not significantly different among the haplo-HCT, MSD, MUD TCD+, and MUD TCD- cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%, respectively, 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 with PTCL-NOS. Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma (TCL). Outcomes of haplo-HCT were comparable to those of matched donor allo-HCT.

Comparison of long-term outcome for AML patients alive free of disease 2 years after allogeneic hematopoietic cell transplantation with umbilical cord blood versus unrelated donor: a study from the ALWP of the EBMT.

Since cord blood transplantation (CBT) has been associated with high graft-versus-leukemia effects and a low incidence of chronic graft-versus-host disease (GVHD), we hypothesized that long-term outcomes might be better in CBT patients than in those given grafts from unrelated donors (UD). Therefore, we performed a landmark study comparing long-term outcomes in acute myeloid leukemia (AML) patients alive and disease-free 2 years after transplantation who received grafts from either CBT or UD. A total of 364 CBT recipients, 2648 UD 10/10 patients and 681 patients given grafts from UD 9/10 were included. Median follow-up was 6.0 years. Five-year leukemia-free survival (LFS) from transplantation was 86% in CBT patients, 84% in UD 10/10 patients (P = 0.36) and 84% in UD 9/10 patients (P = 0.86). On multivariate analysis, donor type had no impact on LFS. Similarly, no impact of donor type was observed on relapse incidence or non-relapse mortality. Factors associated with poorer LFS on multivariate analysis included higher age at transplantation (P < 0.001), male gender (P < 0.001), second complete remission (CR2) versus CR1 (P = 0.05), secondary AML (P = 0.01), antecedent of chronic GVHD (P < 0.001) and poor-risk cytogenetics (P = 0.01). In conclusion, our study shows that long-term outcome for AML patients in CR two years after transplantation is not impacted by donor type.