Measurable Residual Disease as Predictor of Post-Day +100 Relapses Following Allografting in Adult AML

• Among patients alive without relapse at day +100, MRD is uncommon but identifies those at increased risk of relapse and worse survival.

• While most patients with pre-HCT MRD clear MRD by day +70-100, their outcomes are substantially worse relative to MRDneg/MRDneg patients.

Measurable residual disease (MRD) by multiparametric flow cytometry (MFC) before allogeneic hematopoietic cell transplantation (HCT) identifies patients at high risk of acute myeloid leukemia (AML) relapse, often occurring early after allografting. To examine the role of MFC MRD testing for the prediction of later relapses, we examined 935 adults with AML or myelodysplastic neoplasm (MDS)/AML transplanted in first or second morphologic remission who underwent bone marrow restaging studies between day 70 and 100 post-HCT and were alive and without relapse by day +100. Of these 136 (15%) had MRD before HCT, whereas only 11 (1%) had MRD at day +70-100. In day +100 landmark analyses, pre-HCT and day +70-100 MFC MRD were both associated with relapse (both P<0.001), relapse-free survival (RFS; both P<0.001) overall survival (OS; both P<0.001), and, for post-HCT MRD, non-relapse mortality (P=0.001) after multivariable adjustment. Importantly, while 126 of the 136 patients (92%) with MRD before HCT tested negative for MRD at day +70-100, their outcomes were inferior to those without MRD before HCT and at day +70-100, with 3-year relapse risk of 40% vs. 15% (P<0.001), 3-year RFS of 50% vs. 72% (P<0.001), and 3-year OS of 56% vs. 76% (P<0.001), whereas 3-year NRM estimates were similar (P=0.53). Thus, despite high MRD conversion rates, outcomes for MRDpos/MRDneg patients are inferior to MRDneg/MRDneg patients, suggesting all patients with pre-HCT MRD should be considered for pre-emptive therapeutic strategies after allografting.