A Meta-analysis Of Effects Of Simultaneous Mutation In NPM1and FLT3Gene On Complete Remission Rate Of Patients With Acute Myeloid Leukemia

Background：The acute myeloid leukemia with normal karyotype with large differences often go tomiddle-prognosis group. The gene mutation of NPM1and FLT3were the most commontypes in acute myeloid leukemia with normal karyotype. Previous studies have found thatthe patients with only NPM1gene mutations had better survival; but the patients with FLT3gene mutations had low remission rate and poor prognosis. Recent studies have shown that,both NPM1and FLT3gene mutation occurs at higher frequency, but which reported itsprognosis varies, and still need a large sample study further validation. In this study, we areaiming to evaluate both NPM1and FLT3gene mutation influence prognosis in acutemyeloid leukemia with normal karyotype by meta-analysis.Objective：To evaluate both NPM1and FLT3gene mutations influence prognosis in acutemyeloid leukemia with normal karyotype by meta-analysis.Methods：The databases such as Medline(1950to2013), CNKI (1994to J2012), WanFang Data(1994to2012) and Wei Pu Data (1989to2012) were searched to collect literatures whichcomparing both NPM1and FLT3mutation influence prognosis in acute myeloid leukemiawith normal karyotype. We adopted blood white blood cell count(WBC), percentage ofbone marrow blasts(%), complete remission rate(CR), overall survival(OS), event-freefreesurvival(EFS), relapse-free survival(RFS) and relapse rate(RR) as result indicator. Twoauthors at least, indenpdently selected studies and extracted data. The data was input andanalysed with Cochrane review manager software(Rev Man5.0) for meta-analyses. Results：Eight studies were eligible for inclusion (N=1035), including394cases subjects ofNPM1+/FLT3-ITD+and641cases subjects of NPM1-/FLT3-ITD-. Meta analysis showedthat there were no statistically significant effects between NPM1+/FLT3-ITD+of NK-AMLand NPM1-/FLT3-ITD-of NK-AML on complete remission rate (CR)[OR=0.71,95%CI(0.45,1.13), p=0.15], Overall survival(OS)[OR=0.96,95%CI(0.70,1.33), p=0.82],event-free survival(EFS)[OR=0.74,95%CI(0.17,2.01), p=0.40], relapse-free survival(RFS)[OR=0.54,95%CI(0.25,1.17), p=0.12] and relapse rate(RR)[OR=1.17,95%CI(0.71,1.93),p=0.53]. However, there were statistically significant effects betwen NPM1+/FLT3-ITD+ofNK-AML and NPM1-/FLT3-ITD-of NK-AML on white blood cell count (WBC)[MD=32.45,95%CI(9.30,55.60), p=0.006] and percentage of bone marrow blasts(%)[MD=15.09,95%CI(97.91,22.26), p<0.001].Conclusions：Meta analysis showed that there were no significant difference betwenNPM1+/FLT3-ITD+of NK-AML and NPM1-/FLT3-ITD-of NK-AML on completeremission (CR), Overall survival (OS), event-free survival (EFS), relapse-free survival(RFS) and relapse rate (RR). But white blood cell count (WBC) and bone marrow blastswere significant increased comparing to NPM1-/FLT3-ITD-of NK-AML. This conclusionneed to be validated by further studies because of limitation of the included trials.