The characteristics of FLT3 mutations in Chinese de novo adolescent and adult ALL patients

2019 
Abstract Background Activating mutations in FLT3 are frequent in acute myeloid leukemia (AML) and have important prognostic and therapeutic implications. Meanwhile, FLT3 aberrations have been detected in a smaller fraction of acute lymphoblastic leukemia (ALL), and their prognostic value are not well established. Therefore, we assessed the FLT3 mutation in Chinese adolescent and adult ALL patients. Methods We have examined a cohort of 117 Chinese de novo adolescent and adult ALL patients enrolled between June 2016 and June 2017 from the First Affiliated Hospital of Soochow University. Prognostic factors for ALL patient population were estimated by Cox regression method. FLT3 mutation was detected by polymerase chain reaction (PCR) and its clinical effect was assessed by Kaplan–Meier curves. Differences in FLT3 mutation rate between subgroups were tested by χ2-test. Results FLT3 mutations accounted for 6.8% (8/117) in our cohort , including 3 ITDs(2.6%) and 5 TKDs(4.3%, 3 D835Y mutations, 1 M664I mutation and 1 I867S mutation),which had no clinical significance on both overall survival (OS) and event free survival(EFS). Alterations in FLT3 occurred more often in early T precursors (ETP) ALL compared with non-ETP-T-ALL (P=0.028). However, the age of onset (P=0.004), initial platelet counts (P=0.018) and transplant status (P=0.007) were independent prognostic factors on OS for ALL cases in multivariate analysis. Conclusions FLT3 mutation was not common in Chinese ALL patients. Age of onset, platelet counts and transplant status rather than FLT3 mutations were independent prognostic variables for ALL cases on OS in our cohort. In spite of small sample size, ETP-ALL may indicate a comparable higher FLT3-mutant rate. Since ETP-ALL has been identified as high-risk subgroup, these data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic hematopoietic stem cell transplantation for FLT3 mutant ETP-ALL.
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