Prognostic Factors Of Allogeneic Hematopoietic Stem Cell Transplantation In Patients With Acute Myeloid Leukemia

Objective To explore the factors influencing the survival outcome of patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT),in order to provide reference for improving the clinical outcome and survival rate of these patients in clinical work.Methods From September 2012 to June 2022,42 patients with AML who were first diagnosed in the Department of Hematology of our hospital(the First Affiliated Hospital of Anhui Medical University)and received allo-HSCT in the later period were selected as the research objects.Retrospective analysis was performed on the effects of age,gender,blood routine indicators,proportion of bone marrow primitive cells at initial diagnosis,post-transplant complications,gene mutation,pre-transplant disease remission status,post-transplant disease recurrence and other factors on overall survival(OS)rate and disease-free survival(DFS)rate of patients after transplantation.The OS rate and DFS rate of patients were statistically described by Kaplan-Meier curve.COX proportional risk regression model was used to analyze univariate and multivariate factors that might affect the prognosis of allo-HSCT patients with AML,so as to identify the risk factors affecting the patients’ OS and DFS after transplantation.Results 1.Among the 42 patients included in the study,there were 20 females(20/42,47.6%)and 22 males(22/42,52.4%).The median age of patients was 30(14-57)years.According to FAB,there were 1 case(1/42,2.4%)in M1,23 cases(23/42,54.8%)in M2,5 cases(5/42,11.9%)in M4,10 cases(10/42,23.8%)in M5,and 3cases(3/42,7.1%)in M6.According to the 2018 National Comprehensive Cancer Network(NCCN)Clinical Practice Guidelines for AML,the patients were stratified according to cytogenetics and molecular biology: 12 cases(12/42,28.6%)in the moderate prognosis group,26 cases(26/42,61.9%)in the poor prognosis group,and 4cases(4/42,9.5%)in the non-grouping group.One patient died of implantation failure,and the other 41 patients received hematopoietic reconstruction.2.40 of the 42 patients were tested for mutated genes at the time of initial diagnosis,and the results showed that the most mutated genes were detected respectively:DNMT3A mutation(13/40,32.5%),FLT3-ITD mutation(10/40,25%),TET2mutation(8/40,20%)and CEBPA mutation(6/40,15%),KIT mutation(6/40,15%).There were 8 cases combined with the two gene mutations and 3 cases combined with the three gene mutations.Among the 6 patients with CEBPA mutation detected,1 patient was detected with FLT3 and WT1 mutation,3 patients with ASXL1 mutation,and 2 patients with ASXL1 mutation were detected with TET2 mutation.All patients underwent allogeneic hematopoietic stem cell transplantation,and were classified according to the compatibility of human leukocyte antigen(HLA).There were 12 cases of sibling HLA complete compatibility,4 cases of unrelated donor HLA complete compatibility,2 cases of umbilical cord blood HLA complete compatibility,and 24 cases of related HLA incomplete compatibility(haplotype compatibility).3.Complete response(CR)was achieved in 25 patients(59.5%)before transplantation,and in 17 patients(40.5%)without CR.Univariate analysis suggested that DNMT3 A mutation before transplantation and disease without CR before transplantation were risk factors affecting the rates of OS and DFS 2 years after transplantation.(1)There were differences in OS(HR 18.63,95%CI 5.09-68.18,P < 0.001)and DFS(HR 17.98,95%CI 4.90-65.99,P < 0.001)between patients with DNMT3 A mutation before transplantation and those without DNMT3 A mutation.The difference was statistically significant.(2)The prognosis of CR and non-CR groups before transplantation was different(HR0.05,95%CI 0.01-0.23,POS< 0.001;HR 0.04,95%CI 0.01-0.21,PDFS< 0.001),the difference was statistically significant.4.Multivariate analysis suggested that DNMT3 A mutation existed before transplantation and no CR(HR 0.08,95%CI 0.01-0.47,POS=0.005;HR 0.07,95%CI0.01-0.48,PDFS=0.006)maybe independent risk factors for OS and DFS after transplantation in AML patients.5.Kaplan-Meier curve was used to further analyze the effects of DNMT3 A mutation and disease remission status before transplantation on the OS rate and DFS rate of patients 2 years after transplantation.The results showed that:(1)The 2-year OS rates of patients with and without DNMT3 A mutation were 0%VS(89.4±5.8)%(P< 0.001).Respectively,the 2-year DFS rates were 0% VS(83.8±7.5)%(P < 0.001).(2)The 2-year OS rates in CR and non-CR groups before transplantation were(91.6±5.7)% VS(19.6±10.9)%(P< 0.001),and the 2-year DFS rates in both groups were(91.6±5.7)% VS 0%(P< 0.001).Conclusion Allo-HSCT after remission is an effective treatment to improve the prognosis of patients with AML.DNMT3 A mutation and disease without CR before transplantation are independent risk factors affecting the prognosis of patients with AML.The presence of DNMT3 A mutation before transplantation and disease not reaching CR before transplantation affected the 2-year OS rate and DFS rate of patients,and the difference was statistically significant.However,the results of multivariate analysis suggested that the 95% confidence interval of the effect of DNMT3 A mutation on prognosis fluctuated greatly,which may be related to the small sample size of this study.In the later stage,the relationship between gene mutation and patient prognosis can be explored by further expanding the sample size.