Are HLA-Haploidentical Relatives a Donor Choice for Patients With Severe Aplastic Anemia? A GATMO-TC Experience

Severe and very severe aplastic anemia (SAA) is associated with poor outcomes without prompt and adequate treatment. While immunosuppressive therapy (IST) remains a valid option, limited availability of horse antithymocyte globulin and relapse rates can hinder success. For patients requiring urgent hematopoietic cell transplantation (HCT) without a matched sibling donor, HLA haploidentical donors are often readily available, with encouraging results in SAA. To primarily evaluate overall survival (OS), and secondarily graft failure (GF), graft-versus-host disease (GVHD), failure-free survival (FFS), GVHD-free and failure-free survival (GFFS) and cytomegalovirus (CMV) reactivation in patients with SAA undergoing T-replete HLA-haploidentical HCT (Haplo-HCT) with posttransplant cyclophosphamide (PT-Cy). Multicenter retrospective cohort study of patients with SAA who underwent Haplo-HCT in Argentina. Participating centers were invited through GATMO-TC (Argentinian Group of Bone Marrow Transplantation and Cellular Therapy). Data from 44 patients (median age, 19 years; range: 3 to 59; 72% male) from 11 centers were analyzed. Haplo-HCT was performed between January 2016 and July 2025. The median time from diagnosis to transplantation was 3.2 months for upfront Haplo-HCT (n = 18) and 11.4 months for delayed Haplo-HCT after IST failure (n = 26). Most patients had a hematopoietic cell transplantation-specific comorbidity index of 0 to 1 (93%). Donors had a median age of 30 years (range, 5 to 54; 76% male) and were predominantly first-degree relatives. Peripheral blood was used as the stem cell source in 61.4% of cases. A Baltimore-type nonmyeloablative conditioning regimen was used in 79.5% of patients with or without rabbit antithymocyte globulin (ATG; median dose: 4.5 mg/kg), and all patients received PT-Cy. One patient developed primary GF and underwent a successful second Haplo-HCT, while another experienced secondary GF and died. The 1-year cumulative incidence of grade 2 to 4 acute GVHD was 36.5%, and the 3-year cumulative incidence of chronic GVHD was 22.2%. Use of ATG in the conditioning regimen, a Baltimore-type regimen, and male donors were associated with a lower incidence of chronic GVHD. No impact of the stem cell source was detected. At three years, OS was 86.4% overall, 94.4% in the upfront group, and 80.8% in the delayed group (P = .218). At three years, FFS was 84.1% and GFFS was 74.7% for the entire cohort. The Baltimore-type regimen was associated with significantly lower rates of CMV reactivation (P = .013). Haploidentical HCT is a feasible and effective treatment option for selected patients with SAA requiring urgent transplantation. Favorable outcomes were observed using nonmyeloablative platforms incorporating PT-Cy and ATG.