Allo-HSCT for acute myeloid leukemia with myelodysplastic-related changes: a clinical analysis
10.3760/cma.j.issn.0253-2727.2021.10.004
- VernacularTitle:异基因造血干细胞移植治疗急性髓系白血病伴骨髓增生异常相关改变75例临床分析
- Author:
Haixiao ZHANG
1
;
Aiming PANG
;
Xin CHEN
;
Rongli ZHANG
;
Weihua ZHAI
;
Qiaoling MA
;
Donglin YANG
;
Jialin WEI
;
Yi HE
;
Sizhou FENG
;
Mingzhe HAN
;
Erlie JIANG
Author Information
1. 中国医学科学院、北京协和医学院血液病医院（中国医学科学院血液学研究所），实验血液学国家重点实验室，国家血液系统疾病临床医学研究中心，天津 300020
- Keywords:
Acute myeloid leukemia with myelodysplastic related changes;
Hematopoietic stem cell transplantation;
Genetic mutations
- From:
Chinese Journal of Hematology
2021;42(10):814-822
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the outcomes and prognostic factors of adults with acute myeloid leukemia with myelodysplastic-related changes (AML-MRC) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . The genetic mutation lineage of patients with AML-MRC and the molecular mutation affecting the transplantation prognosis was discussed.Methods:The clinical data of 75 patients with AML-MRC who underwent allo-HACT from 2006 to 2020 were retrospectively analyzed for clinical characteristics, survival, relapse-related indicators, and risk factors affecting transplantation prognosis. Additionally, the clinical characteristics and prognosis of multilineage dysplasia (M) group, history of myelodysplastic syndrome (MDS) or myelodysplastic syndrome/myelodysplastic proliferative tumor (MDS/MPN) (H) group, and MDS related cytogenetic abnormalities (C) group were compared. The bone marrow of 43 patients underwent targeting second-generation sequencing (137 genes) .Results:①There were 41 males and 34 females with a median age of 41 (18-56) years, a median follow-up time of 35 (95% CI 30-49) months, and a median survival time (OS) of 78 (95% CI 23-) months. Three-year OS and event-free survival (EFS) were 57.1% (95% CI 45.6%-71.4%) and 52.0% (95% CI 40.8%-66.1%) . Also, the three-year cumulative recurrence rate (CIR) and transplant-related mortality rate (TRM) were 26.8% (95% CI 16.6%-30.0%) and 22.7% (95% CI 13.2%-33.8%) , respectively. Furthermore, multivariate analysis revealed that pre-transplant non-CR1 status was an independent risk factor for 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. ②Among the 75 patients, 59 (78.7%) were in group H, 20 had received demethylation drugs before turning to AML and nine cases (12.0%) in group C and seven cases (9.3%) in group M. There was no significant difference in the three-year OS and EFS among the three groups[group M vs H vs C: OS: 71.4% (95% CI 44.7%-100.0%) vs 55.0% (95% CI 41.8%-72.5%) vs 55.6% (95% CI 31.0%-99.7%) , P=0.700; EFS: 71.4% (95% CI 44.7%-100.0%) vs 46.5% (95% CI 34.0%-63.8%) vs 55.6% (95% CI 31.0%-99.7%) , P=0.600]. Compared with primary and secondary AML-MRC, there was no statistically significant difference in the three-year OS and EFS[61.9% (95% CI 41.9%-91.4%) vs 55.0% (95% CI 41.8%-72.5%) , P=0.600; 61.9% (95% CI 41.9%-91.4%) vs 46.5% (95% CI 34.0%-63.8%) , P=0.400]. Furthermore, there was no significant difference in the time to AML between patients who received demethylation treatment before (20 cases) and those who did not (39 cases) [195 (16-937) d vs 162 (9-3167) d, P=0.804]. Moreover, there were no statistically significant differences in the three-year OS and EFS between the two groups ( P=0.400, P=0.700) . ③ NGS test was performed on bone marrow samples of 43 patients (57.3%) , and 73 mutation types were found. Additionally, U2AF1 had the highest mutation incidence (11 cases, 25.6%) , and more than 10% were found: RUNX1 (ten cases, 23.3%) , NRAS (ten cases, 23.3%) , ASXL1 (six cases, 14.0%) , PTPN11 (five cases, 11.6%) , TET2 (five cases, 11.6%) . Univariate analysis showed U2AF1[ P=0.875, HR=1.110 (95% CI 0.295-4.195) ], RUNX1[ P=0.685, HR=0.728 (95% CI 0.157-3.375) ], NRAS[ P=0.919, HR=0.923 (95% CI 0.196-4.334) ] mutation did not affect OS. Conclusion:Chromosome abnormality of -5/5q-, cGVHD, and non-CR1 status before transplantation were independent risk factors for OS in patients with allo-HSCT and AML-MRC. Additionally, the MHC subgroup classification was not a factor affecting the prognosis of transplantation. Treatment with demethylated drugs may not delay MDS turning to AML and prolong the OS after transplantation.
