Impact of Minimal Residual Disease Status on Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia

This study assessed how measurable residual disease (MRD) status at the time of allogeneic hematopoietic stem cell transplantation (allo-HSCT) impacts post-transplant outcomes in acute myeloid leukemia (AML) patients. We retrospectively analyzed AML patients who underwent allo-HSCT from matched related donors (MRD) or matched unrelated donors (MUD) between 2013 and 2018 using the Center for International Blood and Marrow Transplant Research (CIBMTR) P-5646 dataset by Ramanathan et al. Multivariate Cox regression analyses were conducted to calculate hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute and chronic graft-versus-host disease (aGVHD, cGVHD), and platelet and neutrophil engraftment. Statistical significance was set at p < 0.05, and R version 4.16 was used for analysis. We included 3,116 patients with AML undergoing allo-HSCT, among whom 471 tested MRD-positive and 2,645 tested MRD-negative before transplant. The baseline characteristics, including age, gender, ethnicity, race, comorbidity index, performance status, donor/recipient match (human leukocyte antigen, cytomegalovirus, and gender), graft type, conditioning regimen, and GVHD prophylaxis were similar between the two groups. In the MRD-positive group, 59% had a Karnofsky performance status ≥90% compared to 51% in the MRD-negative group (p=0.004). Myeloablative conditioning was used in 66% of the MRD-positive group compared to 55% in the MRD-negative group (p<0.001). In the multivariate regression analyses, MRD-positive status pre-allo-HSCT independently predicted poor OS (41% vs 59%; HR 1.83, 95% CI 1.60-2.09, p<0.001), poor DFS (29% vs 47%; HR 1.94, 95% CI 1.71-2.19, p<0.001), and higher relapse rates (57% vs 37%; HR 2.21, HR 1.92-2.53, p<0.001). Slightly higher rates of grade 2-4 aGVHD (HR 1.18, 95% CI 1.01-1.38, p=0.036) and cGVHD (HR 1.29, 95% CI 1.01-1.41, p=0.043) and slower platelet engraftment (HR 0.73, 95% CI 0.66-0.82, p<0.001) were noted in the MRD-positive group. Neutrophil engraftment (p=0.269) and NRM (p=0.685) did not significantly differ between the two groups. The outcomes analyses were adjusted for conditioning regimen and other significant predictors. The study's findings underscore the potential benefits of eradicating MRD before allo-HSCT. Pre-transplant MRD status is predictive of post-allo-HSCT outcomes, with MRD positivity correlating with decreased overall and disease-free survival and a higher incidence of relapse regardless of conditioning regimen intensity. Strategies to eradicate MRD before allo-HSCT may improve outcomes in AML patients undergoing allogeneic transplantation.