Posttransplant MRD and T-cell chimerism status predict outcomes in patients allografted with AML/MDS.

Allogeneic stem-cell transplantation allows the delivery of curative graft-versus-leukemia (GVL) in patients with acute myeloid leukemia/myelodysplasia (AML/MDS). Surveillance of T-cell chimerism, measurable residual disease (MRD) and blast HLA-DR expression may inform whether GVL effectiveness is reduced. We report the prognostic impact of these biomarkers in patients allografted for AML/MDS. 187 patients from FIGARO, a randomized trial of reduced-intensity conditioning regimens in AML/MDS, were alive and relapse-free, at the first MRD timepoint and provided bone marrow for flow cytometric MRD monitoring and blood samples for T-cell chimerism analysis, requested to month+12. 29 (15.5%) patients had at least one MRD-positive result post-transplant. MRD-positivity was associated with reduced overall survival (OS) (HR:2.18, p=0.0028) as a time-varying Cox variable and remained significant irrespective of pre-transplant MRD status in multivariate analyses (p<0.001). 94 patients had sequential MRD with T-cell chimerism results at months+3/+6. Patients with full donor T-cell chimerism (FDTC) had an improved OS as compared with patients with mixed-donor T-cell chimerism (MDTC) (adjusted-HR=0.4, p=0.0019). In patients with MDTC (month+3 or +6), MRD-positivity was associated with decreased 2yr-OS (34.3% [95% CI:11.6-58.7] versus MRD-negative 71.4% [95% CI:52.2-84.0], p=0.001). In contrast, in the group with FDTC, MRD was infrequent and did not impact outcome. Amongst patients with post-transplant MRD-positivity, decreased HLA-DR expression on blasts significantly reduced OS, supporting this as a mechanism for GVL escape. Post-transplant MRD is an important predictor of outcome in patients allografted for AML/MDS and is most informative when combined with T-cell chimerism results, underlining the importance of a GVL effect in AML/MDS.