Excellent Prognosis of Low-Risk Myelodysplastic Syndromes (MDS) Without Detectable Myeloid-Related Mutations

Background: Unexplained cytopenia (UC) and low-risk myelodysplastic syndrome (MDS) are distinguished mainly by morphologic dysplasia, which sometimes shows inter-observer discrepancy. We hypothesized that gene mutations are strong prognostic factors for these low-risk patients. Materials and methods: We enrolled patients from 4 medical centers with unexplained cytopenia of at least 1 lineage. Diagnosis of low-risk MDS was made according to WHO 2016 classification and a revised international prognostic scoring system (R-IPSS) score of = 3.5. DNA was extracted from bone marrow or blood and sequenced by targeted next generation sequencing (NGS). Results: One hundred twenty-one patients were recruited: 25% with UC and 75% with low-risk MDS. Complete blood counts were similar, but low-r isk MDS patients carried higher numbers of mutations (1 vs. 0; P =.04) than UC patients. Overall, the most frequent mutated genes were TET2 (14.6%), SF3B1 (12.2%), and ASXL1 (9.7%). Survival rates of low-risk MDS patients versus UC patients were not significantly different. UC patients and low-risk MDS patients without genetic abnormalities showed superior 5-year progression free survival compared to MDS patients with mutations (100% vs. 76.0%; P =.005). Overall, ASXL1 mutations were associated with decreased 4-year overall survival compared to wild-type (59% vs. 31%; P =.01). In a multivariate analysis, ASXL1 and DNMT3A mutations in low-risk MDS patients were associated with a higher risk of disease progression with hazard ratios of 7.88 (95% CI 1.76-35.32, P =.01) and 7.45 (95% CI 1.61-34.46, P =.01), respectively. Conclusion: Mutation detection is important for proper risk stratification of patients presenting with idiopathic cytopenia.

Automated summary

Mutation detection is important for proper risk stratification of patients presenting with idiopathic cytopenia. ASXL1 and DNMT3A mutations in low-risk MDS patients are associated with a higher risk of disease progression.