Early Mixed Donor Chimerism is a Strong Negative Prognostic Indicator in Allogeneic Stem Cell Transplant for AML and MDS

•Both day 30 whole blood and T-cell mixed donor chimerism were individually associated with an increased risk of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome.•Worse overall and relapse-free survival was demonstrated when whole blood or T-cell chimerism were mixed at days 30, 60 and 90.•Evaluating the kinetics of chimerism over the first 90 days provided additional information for prognosticating relapse than absolute chimerism values at individual time points in both whole blood day 30 to 90 [HR, 1.75 (95% CI, 1.04 to 2.94); P < .035] and T-cell day 60 to 90 [HR, 1.32 (95% CI, 1.03, 1.69); P < .29] supporting the rationale for sequential monitoring of chimerism rather than single measurements.•Prospective randomized controlled trials are needed to evaluate the benefit of pre-emptive approaches such as tapering immunosuppression, donor lymphocyte infusions, second allogeneic stem cell transplants, and maintenance therapies to treat mixed chimerism and establish it as an actionable predictive biomarker post-transplant. Allogeneic bone marrow transplantation remains the most potent curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) due to the graft-versus-tumor effect provided by donor cells. Donor chimerism is utilized early after transplantation to evaluate engraftment and to monitor the persistence of donor hematopoiesis. Literature is conflicting regarding to the prognostic utility of early mixed donor chimerism, chimerism kinetic patterns as well as factors associated with it and we sought to clarify this uncertainty. In this single-centre retrospective analysis, 141 adults aged 18 years of age or older with AML (n = 104) and MDS (n = 37) who received their first transplant from HLA matched related, matched unrelated or mismatched related (haploidentical) donors between 2016 and 2022 and had at least day 30 chimerism measured were included. Approximately 30% received post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis and 67% of subjects received reduced-intensity conditioning. Chimerism was measured using STR-PCR from unfractionated peripheral blood mononuclear cells (whole blood; WB) and CD3+ (T cell; TC) compartment at each time point. Complete donor chimerism was defined as ≥95% whereas