Haploidentical Hematopoietic Stem Cell Transplantation for AML Patients with Persistent Molecular MRD
摘要Objective The combined use of quantitative real-time polymerase chain reaction(qPCR)and next-generation sequenc-ing(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).Methods We included 148 acute myeloid leukemia(AML)patients who were in first complete remission(CR1)and under-went 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.Results 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.Conclusion 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.
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