Allo-HSCT For Treatment Of Acute Myeloid Leukemia With Mylodysplastic Related Changes:outcomes And Prognostic Factors

OBJECTIVE:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in the treatment of acute myeloid leukemia with myelodysplastic related changes(AML-MRC),and to analyze the prognostic factors.The genetic mutation lineage of AML-MRC patients was analyzed,and the molecular biological characteristics affecting the transplantation prognosis were discussed.METHODS:The clinical data of 75 patients with AML-MRC who underwent allo-HSCT in our center from 2006 to 2020 were retrospectively reviewed.Clinical characteristics,survival and relapse related indicators,and risk factors affecting transplantation prognosis of AML-MRC patients were analyzed.The clinical characteristics of pathological hematopoiesis(M)group,myelodysplastic syndrome(MDS)group,history of myelodysplastic syndrome/myelodysplastic proliferative tumor(MDS/MPN)group(H)group,and MDS related cytogenetic abnormalities(C)group were compared and their effects on transplantation prognosis were compared.The gene mutation lineages of bone marrow of 43 patients were observed by targeting second-generation sequencing(137 genes),and the effect of gene mutation on survival was analyzed.RESULTS:The median follow-up time was 17.8(1-180)months,3-year overall survival(OS)and event-free survival(EFS)were 57.1%(95%CI 45.6%-71.4%)and 52%(95%CI 40.8%-66.1%)after transplantation.The 3-year cumulative recurrence rate(CIR)and transplant-related mortality rate(TRM)were 26.8%and 22.7%,respectively.Multivariate analysis showed that pre-transplant non-CR1 status was an independent predictor of post-transplant OS and EFS.Other independent risk factors for OS included abnormal karyotype of-5/5q-chromosome and the absence of chronic graft-versus-host disease(cGVHD)after transplantation.2.Among the 75 patients,59(78.7%)were in group H,including 20 patients who had received demethylation drug treatment before conversion,9(12%)were in group C and 7(9.3%)were in group M.There was no significant difference in OS and EFS among the three groups after transplantation(OS:P=0.7;EFS:P=0.6).Compared with primary AML-MRC and secondary AML-MRC,there was no statistically significant difference in OS and EFS after transplantation(OS:P=0.6;EFS:P=0.4).There was no statistically significant difference in time to AML between the 20 patients who received demethylation treatment before transforming into AML and the 39 patients who did not receive demethylation treatment(P=0.2),and there was no statistically significant difference in OS and EFS between the two groups(OS:P=0.4;EFS:P=0.7).3.NGS test was performed on bone marrow samples of 43 patients(57.3%),and a total of 73 mutation types were found.U2AF1 had the highest mutation incidence(11 cases,26%),and more than 10%were found:RUNX1(10,23%),NRAS(10,23%),ASXL1(6,14%),PTPN11(5,12%),TET2(5,12%).Univariate analysis showed U2AF1[P=0.88,HR=1.1(95%CI:0,29-4.2)],RUNX1[P=0.69,HR=0.73(95%CI:0.16-3.4)],NRAS[P=0.92,HR=0.92(95%CI:0.2-4.3)]mutation is not a factor affecting OS.CONCLUSION:-5/5q-chromosome abnormality,cGVHD,and non-CR1 status before transplantation were independent risk factors for OS in AML-MRC patients after transplantation.The AML-MHC subgroup classification was not a factor affecting the prognosis of transplantation.Treatment with demethylated drugs may not delay the whitening of MDS patients and prolong the OS after transplantation.The molecular biological characteristics affecting the prognosis of allo-HSCT remain to be explored.