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. 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) . ①There were 41 males and 34 females with a median age of 41 (18-56) years, a median follow-up time of 35 (95% 30-49) months, and a median survival time (OS) of 78 (95% 23-) months. Three-year OS and event-free survival (EFS) were 57.1% (95% 45.6%-71.4%) and 52.0% (95% 40.8%-66.1%) . Also, the three-year cumulative recurrence rate (CIR) and transplant-related mortality rate (TRM) were 26.8% (95% 16.6%-30.0%) and 22.7% (95% 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 H C: OS: 71.4% (95% 44.7%-100.0%) 55.0% (95% 41.8%-72.5%) 55.6% (95% 31.0%-99.7%) , =0.700; EFS: 71.4% (95% 44.7%-100.0%) 46.5% (95% 34.0%-63.8%) 55.6% (95% 31.0%-99.7%) , =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% 41.9%-91.4%) 55.0% (95% 41.8%-72.5%) , =0.600; 61.9% (95% 41.9%-91.4%) 46.5% (95% 34.0%-63.8%) , =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 162 (9-3167) d, =0.804]. Moreover, there were no statistically significant differences in the three-year OS and EFS between the two groups (=0.400, =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[=0.875, =1.110 (95% 0.295-4.195) ], RUNX1[=0.685, =0.728 (95% 0.157-3.375) ], NRAS[=0.919, =0.923 (95% 0.196-4.334) ] mutation did not affect OS. 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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607026 | PMC |
http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2021.10.004 | DOI Listing |
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