Mixed T-cell chimerism at 3 months predicts late relapse in acute myeloid leukemia after allogeneic stem cell transplantation

Abstract Relapse remains the leading cause of treatment failure after allogeneic stem cell transplantation (HCT) in acute myeloid leukemia (AML), yet predictors of late relapse remain poorly defined. We conducted a multicenter retrospective study including 388 patients with AML, representing a disease-specific cohort undergoing first HCT across six Scandinavian centers to evaluate the prognostic role of early T-cell chimerism assessed at three months post-HCT. Mixed T-cell chimerism (MTC) was defined as < 95% donor-derived CD3 + T cells. Among patients alive and relapse-free at 12 months, three-month MTC was associated with a significantly higher 5-year cumulative incidence of relapse compared with complete T-cell chimerism (29% vs 17%, p = 0.024) and inferior 5-year RFS (62% vs 74%, p = 0.017). In contrast, pre-HCT measurable residual disease (MRD) was primarily associated with early relapse and showed a weaker association with relapse beyond 12 months. Exploratory analyses suggested that the adverse impact of pre-HCT MRD-positivity was most pronounced among patients with MTC. These findings indicate a temporal distinction in relapse dynamics, in which residual disease burden drives early relapse, whereas impaired immune reconstitution is associated with late relapse. Early T-cell chimerism may therefore identify patients at increased risk of late relapse and could contribute to improved post-HCT risk stratification.