Impression Of Different Scoring Systems And Gene Mutations For The Prognosis Of Myelodysplastic Syndrome(MDS)

Purposes MDS is a heterogeneous disease with diverse clinical manifestations,and an effective prognostic evaluation tool for MDS patients is needed.To achieve more accurate prognosis assessment for Chinese MDS patients,here we examined several scoring systems and explored the implications of gene mutations.Methods The prognostic conditions were stratified against three different score systems(International Prognostic Scoring System(IPSS),WHO Prognostic Scoring System(WPSS),and Revised International Prognostic Scoring System(IPSS-R))were retrospectively applied to 110 MDS patients in study cohort in our hospital and the prognostic conditions were stratified respectively.Furthermore,genetic mutations were identified in 84 out of 110 patients and their association with overall survival(OS)were determined.A new model based on our data incorporating genetic information and IPSS-R was established,and the value was then validated in a 55-patient independent cohort.Results IPSS-R out-performed the others,since it had less overlaps in survival curve,especially in the relatively low-risk group.Among them,fifty-three patients had at least one-point mutation,including thirty-five patients with normal karyotypes.The presence of TP53 mutations,but not TET2,DNMT3 A or ASXL1 mutations was significantly correlated with shorter OS.A new model incorporating IPSS-R and TP53 mutations into survival analysis was proposed,and the prognostic value of this model was validated to be predominant in a 55-patient cohort.Conclusions Our data suggested IPSS-R was more suitable for Chinese population.Attentions should be paid to the unfavorable mutations that might exert impact on the survival,especially in patients with relatively low risk.Purposes Myelodysplastic syndromes(MDS)are characterized by variable degrees of clinical outcomes.Until now,hypomethylating agents(HMAs)are the only drugs that have been approved by FDA in remedying this complicated prognosis disease,but without satisfactory outcome.So,biomarkers of better clinical outcome are of great significance.Many studies have already reported the potential prognostic value of DNA methylation pathway related gene(TET2/DNMT3A/IDH)mutations in demethylation therapy patients,with controversial results.Therefore,a meta-analysis was performed to investigate their prognostic impact on HMAs treated MDS.Methods Databases,including Pub Med,Embase,web of science and the Cochrane Library,were searched for relevant studies published up to 29 May 2018.Overall response rate(ORR)and overall survival(OS)were selected as endpoints.We extracted odds ratio to evaluate the effect of mutations on ORR,and the corresponding hazard ratios and their 95% confidence intervals for OS.Results A total of 13 cohort studies,covering 1398 patients with MDS treated by HMAs were included in the final meta-analysis.Our results indicated that DNMT3 A mutations had a favorable impact(P=0.008)and TET2 mutations,which showed no significance(P=0.06)in all included patients,could imply good efficacy in some subgroups on ORR.However,none advantages of mutations on ORR translated into a benefit in overall survival.Conclusions This meta-analysis indicates one favorable factor,DNMT3 A mutations,on ORR in MDS patients with HMAs therapy.The identification of mutations in DNMT3 A can improve clinical efficacy and help make treatment decisions.