Haploidentical Hematopoietic Stem Cell Transplantation for AML Patients with Persistent Molecular MRD

The combined use of quantitative real-time polymerase chain reaction (qPCR) and next-generation sequencing (NGS) to detect molecular measurable residual disease (mMRD) has been shown to have prognostic value for patients undergoing matched-hematopoietic stem cell transplantation (HSCT). However, there have been no related studies in the context of haploidentical HSCT (haplo-HSCT).

We included 148 acute myeloid leukemia (AML) patients who were in first complete remission (CR1) and underwent HSCT at Union Hospital (Wuhan, China) between 2019 and 2023. Among them, 28 patients were mMRD (+) before transplantation according to PCR/NGS. Then, on the basis of the 2017 European Leukemia Net (ELN) risk stratification, we randomly enrolled 56 mMRD (-) patients at a 1:2 ratio. Finally, we compared the outcomes, including overall survival (OS), cumulative incidence of relapse (CIR), leukemia-free survival (LFS), and nonrelapse mortality (NRM), between the two groups.

Persisting mMRD predicts worse long-term clinical outcomes in AML patients who received haplo-HSCT. The 2-year OS and LFS between the mMRD (+) and mMRD (-) groups were 77.1% (95%CI 62.5-95.2) versus 92.3% (95%CI 85.3-99.9) (P = 0.044) and 72.7% (95%CI 56.9-92.8) versus 90.7% (95%CI 83.2-98.8) (P = 0.003), respectively. The results of multivariate analysis revealed that mMRD (+) patients had worse OS and LFS than control patients did and that the mMRD (+) score was an independent prognostic factor for OS and LFS.

Pre-HSCT mMRD has predictive value for haplo-HSCT outcomes in AML patients. Patients who are mMRD (+) before transplantation have poorer OS and LFS. For these patients, intensified myeloablative conditioning (MAC), rapid reduction in immunosuppressive agents after 30 days, and pro-donor lymphocyte infusion (DLI) can improve post-transplant outcomes.