FLT3-ITD with DNMT3A R882 double mutation is a poor prognostic factor in Chinese patients with acute myeloid leukemia after chemotherapy or allogeneic hematopoietic stem cell transplantation

2017 ◽  
Vol 106 (4) ◽  
pp. 552-561 ◽  
Author(s):  
Shanhao Tang ◽  
Hongjie Shen ◽  
Xinliang Mao ◽  
Haiping Dai ◽  
Xiaming Zhu ◽  
...  
Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5256-5256
Author(s):  
Jie Sun ◽  
Jingsong He ◽  
Guoqing Wei ◽  
Weiyan Zheng ◽  
Jimin Shi ◽  
...  

Abstract Internal tandem duplication of the FLT3 gene (FLT3-ITD) is one of most common genetic mutations found in patients with acute myeloid leukemia (AML). Although FLT3-ITD has been widely studied and used as an important prognostic indicator of AML in the western world, its association with disease features and prognosis in Chinese AML patients to date has rarely been investigated.In this study, 177 Chinese patients with AML were enrolled including a FLT3-ITD mutation positive group (n = 83) and a FLT3-ITD mutation negative group (n = 94).In FLT3-ITD-positive AML patients, the number of patients whose peripheral blood leucocyte count (≥ 100 × 109/L) before treatment was significantly higher than in FLT3-ITD negative patients (32.1% vs 7.6%), but comparing to FLT3-ITD mutation negative patients, 1 year and 2 year event free survival rates (EFSR) of FLT3-ITD-positive AML patients was lower ((37.0% vs 56.0%) and (14.8% vs 38.4%)), and also their 1 year and 2 year OS rates were significantly lower ( (50% vs 100%) and (18.0% vs 36.5%)). However, it was found that the rate of induced remissions in FLT3-ITD-positive AML patients was much lower than in negative patients (39.4% vs 56.0%). The median survival time of the FLT3-ITD+/NPM1- group (n = 39) was superior to the FLT3-ITD+/NPM1+ group (n = 27) (16.1 months vs 5.8 months). Lastly, after comparing chemotherapy regimes, we found that the allogeneic hematopoietic stem cell transplantation treatment method significantly improved the survival rate of FLT-ITD positive AML patients (not reached vs 14.5 months). Therefore, for FLT3-ITD-positive Chinese patients with AML, the relative rate of complication with leucocyte was increased; both the event free and overall survival rates were lower, these characteristics are the same as the FLT3-ITD-positive patients in western countries. The lower induced remission rate and shorter survival time suggested FLT3-ITD+/NPM1+ mutation is inferior to FLT3-ITD+/NPM1- mutation, which is not consistant with most reports. In addition, allogeneic hematopoietic stem cell transplantation was clearly an effective treatment for patients with FLT-ITD positive AML in China. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Andrés R. Rettig ◽  
Gabriele Ihorst ◽  
Hartmut Bertz ◽  
Michael Lübbert ◽  
Reinhard Marks ◽  
...  

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for acute myeloid leukemia (AML). The inherent graft-versus-leukemia activity (GvL) may be optimized by donor lymphocyte infusions (DLI). Here we present our single-center experience of DLI use patterns and effectiveness, based on 342 consecutive adult patients receiving a first allo-HSCT for AML between 2009 and 2017. The median age at transplantation was 57 years (range 19–79), and the pre-transplant status was active disease in 58% and complete remission (CR) in 42% of cases. In a combined landmark analysis, patients in CR on day +30 and alive on day +100 were included. In this cohort (n=292), 93 patients received cryopreserved aliquots of peripheral blood-derived grafts for DLI (32%) and median survival was 55.7 months (2-year/5-year probability: 62%/49%). Median survival for patients receiving a first dose of DLI “preemptively,” in the absence of relapse and guided by risk marker monitoring (preDLI; n=42), or only after hematological relapse (relDLI; n=51) was 40.9 months (2-year/5-year: 64%/43%) vs 10.4 months (2-year/5-year: 26%/10%), respectively. Survival was inferior when preDLI was initiated at a time of genetic risk marker detection vs mixed chimerism or clinical risk only. Time to first-dose preDLI vs time to first-dose relDLI was similar, suggesting that early warning and intrinsically lower dynamics of AML recurrence may contribute to effectiveness of preDLI-modified GvL activity. Future refinements of the preemptive DLI concept will benefit from collaborative efforts to diagnose measurable residual disease more reliably across the heterogeneous genomic spectrum of AML.


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