In a study of 401 patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) evolving from MDS (MDS/AML), researchers found that ASXL1, RUNX1, and TP53 mutations were independent predictors of higher rates of relapse and lower overall survival (p values <0.001 and p=0.017, respectively) after hematopoietic cell transplantation (HCT) in both patients with MDS and MDS/AML.
The researchers used massively parallel sequencing to examine tumor samples collected pre-transplant for somatic mutations in 34 recurrently mutated genes in myeloid neoplasms. Overall, 87% of patients carried 1 or more oncogenic mutations.
The study showed that the impact of ASXL1, RUNX1, and TP53 mutations on post-transplant survival was independent of the revised International Prognostic Scoring System (IPSS-R). The researchers also found that combining somatic mutations and IPSS-R risk improved the ability to stratify patients by capturing more prognostic information at an individual level. Based on the improved measures, the authors suggest that high-risk patients may benefit from undergoing HCT at an early disease stage and discuss the possible use of post-HCT prophylaxis to prevent relapse.
The researchers concluded that “accounting for these genetic lesions may improve the prognostication precision in clinical practice and in designing clinical trials.”