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Prognostic analysis of acute myeloid leukemia with FLT3-ITD and DNMT3A R882 mutations after allogeneic hematopoietic stem cell transplantation and their clinical features

摘要FLT3-ITD and DNMT3A R882 mutations are both independent factors for poor prognosis of acute my eloid leukemia(AML).Allogeneic hematopoietic stem cell transplantation (allo-HSCT)has been confirmed to improve the prognosis of AMLwith either of gene mutations.However, the prognosis of AMLwith FLT3-ITD and DNMT3A R882 mutations after transplantation has been rarely reported.To analyze the clinical outcome of AMLpatients with the double mutations after allo-HSCT.Genetic mutation sets in bone marrow(including FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD, and NMP1)of 241 AMLpatients were detected at diagnosis using direct sequencing method, and their clinical data were also retrospectively analyzed.These patients were grouped according to the genetic mutation types, and their transplantation prognoses results, as well as related factors affecting prognosis, were analyzed.Results: ()The 241 AMLpatients were divided into four groups: FLT3-ITD+DNMT3A R882+, FLT3-ITD+DNMT3A R882-, FLT3-ITD-DNMT3A R882+and FLT3-ITD-DNMT3A R882-groups, which consisted of 19,38,21 and 163 patients, respectively.)Patients with FLT3-ITD+DNMT3A R882+have high white blood cell count and a low complete remission rate after first induction chemotherapy(52.6%), which are common in M5、 M2、M4 with normal chromosome karyotype, higher early cumulative incidence of relapse (6m-CIR36.8± 1.3 %、 12m-CIR49.7± 1.6%) and cumulative mortality rate (6m-CM R26.3± 10.1%、 12m-CMR48.5± 11.8%).()2-year CIRof the FLT3-ITD+DNMT3A R882+was (72.2±2.7%), which was significandy higher than that of the FLT3-ITD+DNMT3A R882-group(38.6±0.7%)and FLT3-ITD-DNMT3A R882+group(36.8± 1.6%), while the 2-year overall survival(OS)rate and 2-year leukocyte-free survival (LFS)rate were(30.9± 13.3%)and (11.3±10.2%), respectively, which were considerably lower than those of the FLT3-ITD+DNMT3A R882-and FLT3-ITD-DNMT3A R882+groups (2y-OS: 67.5±7.8%, 61.4± 12.4%;2y-LFS: 47.9±8.4%, 56.8± 12.5%).Meanwhile, the 2-year CIRrates of the FLT3-ITD+DNMT3A R882-and FLT3-ITD-DNMT3A R882+groups were significantly higher than that of the FLT3-ITD-DNMT3A R882-group (16.3±0.1%), while their 2-year OSrate and 2-year LFSrate were significantly lower than those of the FLT3-ITD-DNMT3A R882-group (2y-OS : 82.5±3.1%、 2y-LFS : 80.9±3.2%).)Univariate and multivariate analyses revealed that disease alleviation prior to transplantation, grade Ⅲ +Vacute graft versus host disease(aGVHD), FLT3-ITD, DNMT3A R882 and FLT3-ITD+DNMT3A R882+were independent factors for poor prognosis after AMLtransplantation.Conclusion: AMLpatients with FLT3-ITD and DNMT3A R882 mutations still present a very poor prognosis after transplantation, manifesting as low OSrate and LFSrates as well as a high CIRrate.Thus, it is necessary to explore prevention strategy for recurrence after transplantation.

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