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 ...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.展开更多
基金supported by grants from the National Key Research and Development Program of China(No.2022YFA1103500)the National Natural Science Foundation of China(No.82170210)。
文摘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.
