Clinical Characters And Prognostic Analysis In Acute Myeloid Leukemia,Myelodysplaisa-Related

Objectives: Acute myeloid leukemia,myelodysplaisa-related(AML-MR)is a new definition renamed by 2022 World Health Organization(WHO)classification of acute myeloid leukemia(AML).It’s a heterogeneous entity with a wide range of features.We investigated the clinical features and prognosis of AML-MR(MR)as well as that of different subgroups.Methods: Clinical data were collected from January 2018 to June 2022 from 237 patients with de novo acute myeloid leukemia at the First Affiliated Hospital of China Medical University,including age,gender,percentage of blast cells in bone marrow and peripheral blood,white blood cell count,hemoglobin level,platelet count,lactate dehydrogenase level,FAB diagnostic types,cytogenetics,second-generation sequencing(65 genes),past medical history,induction therapy regimen,remission and replase status,and whether hematopoietic stem cell transplantation(HSCT)was performed,etc.Clinical characteristics of MR and subgroups under the new criteria were analyzed and prognostic analysis was performed.Results:(1)AML-MR(MR)group patients are older and male-dominated,with lower blast cells percentage in peripheral blood(PB),WBC count and HGB level.In addition,complete remission rate(CRR),overall response rate(ORR)and overall survival(OS)are inferior as well.MR patients share a similar clinical features with MRC patients under2016 WHO classification of WHO.Immunophenotyping shows high expression of CD34,low expression of MPO,CD13,CD64,CD123,CD4,CD9,CD56.Cytogenetics includes normal karyotype,complex karyotype,trisomy karyotype and del(5q),while others are less than 5%.Fifty seven genes are detected in the whole entity,however,eight genes are missing in MR patients.TET2,ASXL1,GATA2,DNMT3 A and RUNX1(equals FLT3-ITD and NRAS)are the five mutations with the highest incidence in MR.RUNX1 and TP53 mutation have high incidence,while GATA2,DNMT3 A,FLT3-ITD and KIT mutation have low incidence compared with other AML patients.(2)Age(HR 1.025,95%CI 1.013-1.037,P<0.001),HGB level over 60g/L(HR 0.554,95%CI 0.392-0.783,P=0.001),blast cell ratio in bone marrow(BM)(HR 1.011,95%CI1.004-1.017,P=0.001),LDH level(HR 1.000,95%CI 1.000-1.001,P<0.001),MR-related cytogenetics(HR 1.661,95%CI 1.112-2.482,P<0.001)and history of MDS or MDS/MPN(HR 1.683,95%CI 1.017-2.786,P=0.043)are independent influencing factors.(3)MR was divided into three groups,MR with MR-related cytogeneic abnormalties(MRC),MR with history of MDS or MDS/MPN(MR-H),and MR with MR-related somatic mutations(MR-M).Subgroup analysis shows that patients in the three groups are similar in age,with no significant differences in other clinical characters other than more mutations in the MR-M group.There are significant differences in ELN risk stratification among the three groups.A vast majority of intermediate risk patients(58.8% vs 7.7% vs 0%,P<0.050)and lower percentage of high risk patients(41.2% vs 92.3% vs 100%,P<0.050)show in MR-H compared with MR-C and MR-M subgroups.The MR-M group has better OS compared to the MR-C group.Moreover,CD13 was lowly expressed in the MR-H group compared with MR-M group,while CD19 is highly expressed in the MR-H group compared with MR-M group.ASXL1 mutation rate is significantly higher in the MR-M group than in the other two groups,FLT3-ITD mutation rate is lower in the MR-C group than in the other two groups,TP53 mutation rate is significantly higher in the MR-C group than in the MR-M group.(4)In MR patients,MR-related gene mutation(HR 0.583,95%CI 0.364-0.932,P=0.024),HGB level(HR 0.989,95%CI 0.980-0.998,P=0.021)and blast cell ratio in bone marrow(BM)(HR 1.011,95%CI 1.003-1.020,P=0.007)are independent influencing factors affecting OS.(5)Under the new 2022 criteria,the differences ware significant in survival analysis for OS and relapse free survival(RFS);the MR-M subgroup had a significantly better OS than the MR-C group in survival analysis for the OS of MR subgroup.Conclusions: AML-MR predicts a poor prognosis.The new criteria is effective in distinguishing this type of leukemia with specific features.It is questionable whether all MR-M patients should be wholely defined as AML-MR or not,prospectively more effective classification criteria need to be refined.