[Risk factors for leukemia transformation in patients with myelodysplastic syndromes]

Objective: To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) . Methods: From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done. Results: The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age (P<0.001) , bone marrow blast percentage (P<0.001) , bone marrow fibrosis (P=0.046) , WHO classification (P<0.001) , IPSS-R (P<0.001) and IPSS-R karyotype group (P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference (P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation (P=0.034) , DNMT3A mutation (P=0.026) , NRAS mutation (P=0.027) and NPM1 mutation (P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups (HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation (HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation (HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion: Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.