Abstract
To assess whether a tolerance-induction regimen could be applied for unrelated (MUD) HCT in severe aplastic anemia (SAA), we retrospectively reviewed our HCT experience using unmanipulated 10/10 HLA-matched bone marrow grafts from matched sibling donors (MSD) versus MUD donors. Conditioning was cyclophosphamide 200 mg/kg (CTX) + rabbit anti-thymocyte globulin 10 mg/kg (ATG) for MSD (n = 9) and total lymphoid irradiation (TLI, 800 cGy) + CTX/ATG for MUD HCT (n = 5). Immunoprophylaxis was cyclosporine A (CSA) and short-course methotrexate. Median patient age was 14.7 years, median time to HCT 1.5 years, and median follow-up 3.0 years. Outcome measures included event-free survival (EFS), time to engraftment, and cumulative incidence of GVHD (CIN of GVHD) for MSD and MUD cohorts. EFS and stable engraftment rate were 100%. CIN of acute GVHD was: MSD, Grade I-II: 1 (11%), Grade III-IV: 0%; MUD, Grade I-II: 1 (20%), Grade III-IV: 1 (20%). CIN of chronic GVHD was: MSD, limited: 1 (11%), extensive: 0%; MUD, limited: 0%, extensive: 0%. All immunosuppressive-compliant patients successfully weaned immunosuppression. Though in limited patients, our results suggest that immunomodulatory TLI added to backbone CTX/ATG conditioning is a promising option for MUD HCT in SAA patients which we will examine in a prospective clinical trial.
