Comparative clinical outcomes of offspring versus matched sibling donor hematopoietic stem cell transplantation in adults aged over 40 years with acute leukemia or Myelodysplastic Syndromes

Abstract Background: With advancing safety profiles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), whether HLA-matched siblings remain the optimal donor choice for older adults (≥40 years) and whether offspring donors demonstrate superior survival outcomes have become pivotal focuses in transplantation research. The goal of this study was to explore the efficacy of haploidentical (younger offspring) or matched sibling allo-HSCT in patients over the age of 40 with acute leukemia (AL) and myelodysplastic syndrome (MDS). Study Design: From December 2018 to September 2023, 156 acute leukemia and myelodysplastic syndrome patients (≥40 years) were transplanted at the Chinese People's Liberation Army (PLA) General Hospital; these patients received allo-HSCT from younger offspring (n=112) or HLA-matched sibling donors (MSDs) (n=44). The incidence of acute graft-versus-host disease (aGVHD) within 100 days, the 5-year cumulative incidence of relapse, nonrelapse mortality (NRM), the 5-year cumulative incidence of chronic graft-versus-host disease, and the 5-year overall survival (OS) and progression-free survival (DFS) rates were compared between the two groups. Results: The median follow-up duration was 1076 (343-2334) days. Compared with MSD HSCT, offspring HSCT had a lower 5-year cumulative incidence of relapse (16.1% vs. 44.9%, p < 0.001) and a lower 5-year cumulative incidence of NRM (offspring: 18.0% vs. MSD: 8.3%, p =0.072). The 5-year overall survival (OS) rate was higher in the offspring donor group (66.2%) than in the MSD HCT group (48.6%) (p =0.274). The 5-year disease-free survival (DFS) rate was 65.9% in the offspring donor group and 46.3% in the MSD group (p =0.094). The cumulative incidence of acute graft-versus-host disease (aGVHD) grades II-IV was 37.5% in the offspring donor group and 25.0% in the MSD group (p =0.140). The 5-year cumulative incidence of chronic graft-versus-host disease (cGVHD) was 10.5% in the offspring donor group and 4.5% in the MSD group (p =0.590). Among CR patients, the offspring donor group demonstrated a clinically meaningful reduction in the 2-year relapse incidence (7.7% vs. 39.5%; p < 0.001), whereas the NRM did not increase compared with that of matched sibling donors (18.0% vs. 8.3%; p=0.072). Survival analysis revealed that offspring donors had superior 2-year OS and DFS (OS: 78.1% vs. 58.9%; p = 0.041; DFS: 77.3% vs. 57.3%; p = 0.042). Conclusions: Our study revealed that, in acute leukemia/MDS patients aged ≥40 years, offspring donors had superior survival outcomes than did MSD donors, especially in patients who achieved CR, demonstrating the clinical benefits of transplantation from offspring donors, including reduced relapse and prolonged OS and DFS.