Impact of clinical characteristics and genetic profiles on outcomes of allogeneic stem cell transplantation with sorafenib maintenance in FLT3-ITD acute myeloid leukemia patients:A multi-center,retrospective study
摘要Objective:Acute myeloid leukemia(AML)patients with internal tandem duplications in the FMS-like tyrosine kinase 3 receptor gene(FLT3-ITD)receiving tyrosine kinase inhibitors maintenance after allogeneic hematopoietic stem cell transplantation(allo-HSCT)demonstrated improved survival outcomes,however,some still experienced relapse during the maintenance.This study aimed to explore risk factors which might be indicators for poor survival after allo-HSCT in this population.Methods:We consecutively enrolled FLT3-ITD AML patients undergoing transplantation at three centers.By integrating genetic profiles with clinical information,we assessed their impact on transplant outcomes.Results:A total of 196 patient were eligible in the analysis,among whom 14%harbored myelodysplasia-related(MR)mutations,including ASXL1,BCOR,EZH2,RUNX1,SF3B1,SRSF2,STAG2,U2AF1,and ZRSR2.Co-mutant MR was independently associated with poorer overall survival(OS)[hazard ratio(HR):2.4,95%confidence interval(95%CI):1.1-5.3,P=0.030].DNMT3A co-mutations strongly predicted adverse survival and relapse[OS:HR:2.1,95%CI:1.0-4.3,P=0.045;relapse-free survival(RFS):HR:2.2,95%CI:1.1-4.1,P=0.017;cumulative incidence of relapse(CIR):HR:2.3,95%CI:1.1-4.8,P=0.030].Compared to patients with negative measurable residual disease(MRD)complete remission(CR),no significant differences were observed in CR patients with positive MRD,while those without CR exhibited significantly inferior outcomes(P=0.003).Conclusions:Patients with myelodysplasia-related gene mutations(MRmut)and/or DNMT3A mutations experienced inferior outcomes after transplantation,requiring further exploration.Furthermore,similar prognoses among CR patients highlighted the need for monitoring specific molecular residual lesions.
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