TP53, RAS pathway and JAK2 V617F mutations were found to predict hematopoietic cell transplantation (HCT) outcomes in patients with myelodysplastic syndromes (MDS), according to a multi-center study analyzing 1,514 transplants reported to the CIBMTR® (Center for International Blood and Marrow Transplant Research®).
In addition, combining key clinical factors with these 3 mutations can be used to identify 6 prognostic MDS subgroups that can guide physicians’ pre- and post-HCT therapy recommendations for their patients.
The researchers performed targeted sequencing of 129 genes on pre-transplant blood samples from 1,514 transplant recipients. Nineteen percent of the cohort had TP53 mutations and a multivariate analysis showed that TP53 mutations were significantly associated with poor overall survival (HR 1.71, 95% CI 1.45-2.02, p<0.001) and a shorter time to relapse (HR 2.03, 1.60-2.58, p<0.001). A multivariate analysis showed that the presence of TP53 mutations predicted these poor outcomes independent of recipient age, performance status, hematologic status at time of HCT, bone marrow blast count and karyotype.
In addition, the results indicated that mutations in any of the genes involved in the RAS signaling pathway were independently associated with a shorter time to relapse (HR 1.56, 1.18-2.05, p<0.002) and that JAK2 V617F mutations were associated with higher non-relapse mortality (HR 2.10, 1.36-3.24, p<0.001).
The adverse prognostic effect of TP53 and JAK2 mutations was similar in reduced-intensity and myeloablative conditioning regimens. In contrast, the effect of RAS pathway mutations on risk of relapse was evident only with reduced-intensity conditioning (p=0.001).
The researchers concluded that the results of the study “will help physicians identify patients for whom a transplant is appropriate, and the intensity of treatment most likely to be effective.”