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.

Abstract

BACKGROUND The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. METHODS We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. RESULTS The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II-IV GVHD (HR 1.6; 95% CI 1.1-2.4) and NRM (HR 2.6; 95% CI 1.5-4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8-1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8-1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4-2.6) and chronic GVHD (HR 1.7; 95% CI 1.2-2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9). CONCLUSIONS The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival.

Abstract

We compared severe graft-versus-host-disease free and relapse-free survival and other transplantation outcomes of acute myeloid leukemia patients given bone marrow without anti-thymocyte globulin, versus peripheral blood stem cells with anti-thymocyte globulin after myeloablative conditioning. In the cohort of patients receiving grafts from a human-leukocyte-antigen matched sibling donor, patients given peripheral blood stem cells with anti-thymocyte globulin (n=1,021) and those given bone marrow without anti-thymocyte globulin (n=1,633) presented comparable severe graft-versus-host-disease free and relapse-free (HR=0.9, 95% CI: 0.8-1.1, P=0.5) and overall (HR=1.0, 95% CI: 0.8-1.2, P=0.8) survival. They had however, a lower incidence of chronic graft-versus-host disease (HR=0.7, 95% CI: 0.6-0.9; P=0.01). In the cohort of patients receiving grafts from human-leukocyte-antigen matched unrelated donor, patients given peripheral blood stem cells with anti-thymocyte globulin (n=2,318) had better severe graft-versus-host-disease free and relapse-free survival than those given bone marrow without anti-thymocyte globulin (n=303) (HR=0.8, 95% CI: 0.6-0.9, P=0.001). They also had a lower incidence of chronic graft-versus-host disease (HR=0.6, 95% CI: 0.5-0.8, P=0.0006) and better overall survival (HR=0.8, 95% CI: 0.6-1.0, P=0.04). In summary, these data suggest that peripheral blood stem cells with anti-thymocyte globulin results in comparable (in the case of sibling donor) or significantly better (in the case of unrelated donor) severe graft-versus-host-disease free and relapse-free survival than bone marrow without anti-thymocyte globulin in patients with acute myeloid leukemia in complete remission receiving grafts after myeloablative conditioning.

Abstract

BACKGROUND The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. METHODS In this retrospective, multicentre study, we assessed the outcomes for adult patients (≥18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3, 2001, and Dec 31, 2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1. We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001-05; epoch 2: 2006-10; and epoch 3: 2011-15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme. FINDINGS We included 106 188 patients in our analysis. The median follow-up was 4.1 years (IQR 1.7-7.7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54.0% [95% CI 53.1-54.8] to 54.6% [53.6-55.6]; matched unrelated: 49.1% [48.0-50.2] to 51.6% [50.7-52.6]; mismatched unrelated: 37.4% [35.7-39.2] to 41.3% [39.5-43.1]; haploidentical: 34.5% [31.4-37.9] to 44.2% [42.1-46.3]; and cord blood 36.3% [33.9-39] to 43.7% [40.8-46.8]). Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different. INTERPRETATION Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms. FUNDING The Varda and Boaz Dotan Research Center in Haemato-Oncology, Tel Aviv University, and the Shalvi Foundation for Research.