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.”
Della Porta MG, et al. J Clin Oncol