Targeted Sequencing Improves DIPSS-Plus Prognostic Scoring in Myelofibrosis Patients Undergoing Allogeneic Transplant

Abstract Primary myelofibrosis (MF) and secondary MF developing after polycythemia vera or essential thrombocythemia are clonal disorders of hematopoiesis. Currently the only therapy offering the potential of cure is hematopoietic cell transplantation (HCT). Several risk classification systems including clinical, hematological and mutational parameters have been proposed. We analyzed the mutational landscape in addition to the Dynamic International Prognostic Scoring System (DIPSS)-plus in 55 MF patients to determine the combined impact on post-HCT outcome. Mutations, analyzed in 75 genes, were most common in JAK2, CALR, ASXL1, TET2, GATA2, EZH2, U2AF1, and ETV6. Patients with three or more mutations in addition to JAK2 or CALR mutations had a higher post-transplant relapse rate and non-relapse mortality than patients with fewer mutations, independent of DIPSS-plus risk. The presence of higher numbers of mutations identified patients at the highest risk of relapse within the highest overall risk group as determined by DIPSS-plus. These findings are consistent with molecular risk classifications for non-transplanted patients and support the proposed transplant risk classification incorporating mutational information.