Evaluation Of A Prognostic Factors For Acute Myeloid Leukemia:A Multicenter,Cohort Study In Northwest China

Acute myeloid leukaemia(AML)is the major leukemia In USA with average of 18860new cases being diagnosed and 10460 estimated deaths per year ~1.And the same is true for Chinese,The crude incidence of AML in China is 2.57 cases per 100 000 people per year,with 1.25 deaths per 100 000 people per year.We have analyzed the clinical and biologic features of patients with previously untreated AML in our cohort.Considering the fact that AML is a heterogeneous disease,clinical results after intensive chemotherapy and information about risk factors can be helpful in assisting clinicians and patients in decision making.The karyotype of the leukemic blasts determined by chromosome banding analysis has been proven to be the most important prognostic parameter in AML.Besides clinical data,NPM1 mutation and RUNX1-RUNX1T1 status as well as immunophenotype e.g.CD34,CD56,are all important prognostic parameters on clinic outcomes.The unfavorable biology of the disease,comorbidities,and significant side effects of intensive cytoreductive treatment make treatment decisions difficult,and possible prognostic information becomes essential to allow a shared decision-making process.MethodThe diagnosis of AML was made according to the French-American-British(FAB)or WHO systems.AML is classified according to the World Health Organization(WHO)Classification of Tumors of Hematopoietic and Lymphoid Tissues,which was last updated in 2008.Patients included in present study were collected since 2007 from Xijing Hospital(XJ),Tangdu(TD)Hospital(Shanxi province)and Lanzhou University Secondary Hospital(LUS)which were the three largest hospital of northwest of China.Prognostic factors can be subdivided into those that are related to the patient and those that are related to the disease.Treatment outcomes were assessed by cytomorphologic evaluation.Response to first induction treatment was determined in a bone marrow(BM)sample on day 15 after the start of treatment.A reduction in blast counts and marrow cellularity was considered as treatment response.Assessment for remission was obtained after 2 cycles of induction treatment in accordance with standard criteria.Overall survival(OS)was measured from the date of diagnosis to death from any cause.Relapse-free survival(RFS)was measured from date of CR until the day of relapse or death from any cause.The following clinical information were collected at primary diagnosis and follow-up:WBC count,platelet count,hemoglobin level,lactase dehydrogenase level,peripheral-blood blasts,de novo AML or non–de novo AML,gender,age,genetic mutations for NPM1 and CEPBA.ResultEach factor's contribution to the CR was determined through multivariate logistic regression.Univariate analysis revealed that the factors impacting the prognosis were:Karyotype(P=0.016),Age(P=0.003),WBC(before blood transfusion,P<0.001),NPM1mutation status(P=0.006),and LDH(P<0.001).Multivariable analyses identified the following characteristics as independent adverse prognostic factors for CR:Age(P=0.002),NPM1 mutation status(P=0.025),and LDH(P<0.001).Univariate analysis revealed that the factors impacting the prognosis weregender,Number of WBC before blood transfusion,Disease status,Karyotype,CD56 expression,and RUNX1-RUNX1T1 status.Multivariable analysis of Cox model showed that the WBC(before blood transfusion,10~9/L,P=0.018),gender(P=0.028),Intermediate risk Karyotype(P<0.001),High risk Karyotype(P<0.001),CD56 expression(P<0.001),and RUNX1-RUNX1T1 status(P=0.015)were all independent predictors for RFS.Multivariable analyses identified the following characteristics as independent adverse prognostic factors for OS:LDH(Less than or equal to 700,P=0.001),CD34 expression(P=0.003),Intermediate risk Karyotype(P<0.001),High risk Karyotype(P<0.001),RUNX1-RUNX1T1(P<0.001),and CEPBA mutation status(P=0.004).The survival of patients with favorable cytogenetics was better(3-year OS of 34.8%)than in the intermediate group(3-year OS of 27.9%).The differences in survival between all groups were statistically significant at the 95%level(log-rank test,P<0.05).There was a trend for longer OS in patients with favorable karyotype,however the difference did not reach statistical significance(P=0.262)due to the relatively small sample size.ConclusionIn our study,we screened many factors for complete response rate,disease-free survival and overall survival and early death.Age and NPM1 mutations is the independent factors in the complete remission rate.WBC,gender,karyotype,CD56,RUNX1-RUNX1T1 mutations are independent prognostic factors for disease-free survival.LDH,CD34,karyotype,RUNX1-RUNX1T1 mutations,CEPBA status are independent factors for overall survival.WBC is high impact independent prognostic factors for early death.Finally,the prognostic factors for acute myeloid leukaemia should be highlighted in the future clinical practice.Taken together,this study,which presents the prognostic factors for acute myeloid leukemia in northwest China,will contribute to prognostic groups with significant implications for the therapeutic strategy for further clinical studies.