Cytogenetic risk-associated outcomes of antithymocyte globulin use in HLA-matched sibling transplantation for acute myeloid leukemia.
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Antithymocyte globulin (ATG) reduces chronic graft-versus-host disease (cGvHD), but concerns remain regarding relapse risk, particularly across cytogenetic risk groups. We retrospectively analyzed 148 acute myeloid leukemia (AML) patients in first remission who underwent matched sibling allogeneic hematopoietic stem cell transplantation (HSCT) across three centers. Patients received transplantation with or without ATG (2.5-5 mg/kg) and were stratified by cytogenetic risk (intermediate, n = 128; adverse, n = 20). Propensity score matching and inverse probability of treatment weighting were applied to adjust for baseline imbalances. After a median follow-up of 91 months, ATG use (n = 96) reduced the incidence of cGvHD (HR 0.43; 95% CI 0.26-0.72; p = 0.001) and improved cGvHD-free relapse-free survival (cGRFS; HR 0.61; 95% CI 0.40-0.93; p = 0.022). No significant differences were observed in overall survival, event-free survival (EFS), relapse, or non-relapse mortality. A significant interaction between ATG and cytogenetic risk (p = 0.025) indicated differential effects by risk profiles. In subgroup analyses, intermediate-risk patients derived consistent benefit, whereas adverse-risk patients (ATG n = 12; non-ATG n = 8) showed higher relapse and inferior EFS. With respect to dose, both 2.5 and 5 mg/kg reduced cGvHD relative to non-ATG; exploratory analyses suggested that 2.5 mg/kg may provide adequate prophylaxis without excess relapse, although statistical power was limited. In conclusion, ATG was associated with reduced cGvHD and improved cGRFS in HSCT for AML, with benefit mainly in intermediate-risk patients. Its use in adverse-risk AML warrants caution, as it may be associated with higher relapse.