Outcomes of HLA-matched unrelated versus haploidentical hematopoietic cell transplantation in acute leukemia: A multicenter observational study in Brazil facilitated by the CIBMTR

Abstract Background: While several studies from high-income countries have evaluated hematopoietic cell transplantation (HCT) using haploidentical related (Haplo) and HLA-matched unrelated donors (MUD), prospective data from low- and middle-income countries remain scarce. Brazil, home to one of the world's largest unrelated donor registries, provides a unique setting to evaluate real-world HCT outcomes using Haplo and MUD. This study aimed to describe major HCT outcomes in adult patients with acute leukemia in complete remission (CR1 or CR2+), using data collected and curated in collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods: This multicenter prospective non-randomized observational study included 501 consecutive patients submitted to HCT from either a Haplo donor or MUD at 21 Brazilian centers between 2018 and 2021 and with data reported to the CIBMTR. Eligible patients were aged ≥18 years, diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), and in CR1 or CR2+ at the time of transplant. The primary outcomes were overall survival (OS) and relapse-free survival (RFS). Secondary endpoints included GVHD-free, relapse-free survival (GRFS), relapse incidence, non-relapse mortality (NRM), and acute/chronic graft-versus-host disease (GVHD). Univariable analyses used Kaplan-Meier and cumulative incidence methods. Multivariable Cox proportional hazards and competing risk models were adjusted for age, disease type and status, graft source, conditioning intensity, donor-recipient cytomegalovirus (CMV) status, and time from diagnosis to transplant. Results: Of the 501 HCT patients, 335 (66.8%) received a Haplo and 166 (33.2%) received a MUD transplant. The median follow-up was 26 months. Baseline characteristics differed between these two groups, including the proportion of CMV-negative donors (43 vs. 34%; p<0.001), the use of bone marrow grafts (54 vs. 39%; p<0.001), and the type of conditioning regimen (myeloablative in 84 vs. 76%; p<0.001), all of which were more common in the MUD group. Time from diagnosis to HCT was considerably longer for MUD recipients, especially in CR1 patients (9 vs. 7 months; p<0.001). Post-transplant cyclophosphamide (PTCy) was used in 92% of Haplo recipients and in 5% of MUD recipients, while antithymocyte globulin (ATG) was used in 91% of MUD and only 1% of Haplo transplants. At 2 years, OS was 61% (Haplo) vs. 66% (MUD; p=0.071), and RFS was 57% vs. 62% (p=0.19). GRFS was 44% (Haplo) vs. 47% (MUD; p=0.49), and NRM was 23% vs. 24% (p=0.96). The 2 -year relapse incidence was 20% for Haplo and 14% for MUD HCT (p=0.069). After adjusting for time to transplant, donor type was not an independent predictor of relapse (HR 1.53; 95% CI, 0.92–2.56; p=0.10). The incidence of grade III–IV aGVHD was 9% vs. 13% (p=0.17), and chronic GVHD was 15% vs. 16% (p=0.85) for Haplo and MUD transplants, respectively. In multivariable models, donor type was not independently associated with OS, RFS, GRFS, relapse, NRM, or GVHD outcomes. Conclusion: We found no difference in OS, RFS, GRFS, GVHD and NRM between Haplo and MUD transplants for patients with acute leukemias in complete remission undergoing HCT in Brazil. These results support the use of either Haplo or MUD grafts as a reasonable alternative for patients lacking an HLA-matched sibling donor. This study also demonstrates the feasibility of conducting multicenter observational studies in a developing country through collaboration between the Brazilian national transplantation society and the CIBMTR.