Donor-Related Factors Affecting Haploidentical HSCT Outcomes in Acute Leukemia: A Single-Center Retrospective Cohort Study of a Modified Combination of Anti-Thymocyte Globulin and Post-Transplant Cyclophosphamide

Abstract

Background and Aims: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) provides curative therapy for patients lacking HLA-matched donors, yet optimal donor characteristics remain uncertain. This study assessed the effect of donor relationship, age, sex, and ABO compatibility on outcomes of haplo-HSCT for acute leukemia under a uniform ATG/post-transplant cyclophosphamide (PTCy)-based protocol. Methods: In this retrospective single-center cohort, 159 adults with acute myeloid or lymphoblastic leukemia received peripheral blood haplo-HSCT following myeloablative busulfan/cyclophosphamide plus ATG and PTCy (2015-2022). Overall survival (OS), disease-free survival (DFS), GVHD-free/relapse-free survival (GRFS), and relapse incidence were analyzed using Kaplan-Meier and Fine-Gray methods; predictors were evaluated by multivariable Cox regression. Results: Of 159 patients, 96/159 (60.4) had AML and 63/159 (39.6) had ALL. Donors were siblings in 90/159 (56.6), parents in 48/159 (30.2), and offspring in 21/159 (13.2). Median recipient age was 27 years (range, 15-59), and median donor age was 31 years (range, 2-65). At 36 months, unadjusted outcomes varied across donor groups. In AML, OS was 52.7 (95 CI, 38.8-64.9) with sibling donors, 52.3 (95 CI, 29.4-71.0) with parent donors, and 32.1 (95 CI, 9.5-57.9) with offspring donors. In ALL, offspring donors were associated with numerically lower survival and higher relapse. In multivariable analysis, ALL (HR, 1.99; 95 CI, 1.25-3.17; p = 0.004), advanced remission status (HR, 1.79; 95 CI, 1.16-2.77; p = 0.01), and older recipient age (HR, 1.03 per year; 95 CI, 1.01-1.05; p < 0.001) were independently associated with worse OS. Donor's age, sex, relationship, and ABO compatibility were not independently associated with major outcomes. Conclusions: In this single-center cohort of adults undergoing haploidentical HSCT with a uniform ATG/PTCy-based platform, donor relationship was associated with descriptive differences in unadjusted outcomes, but it was not an independent predictor in multivariable models. The inferior outcomes observed with offspring donors appeared to be influenced in part by older recipient age.