Impact of Molecular Genetics on Outcome in Myelofibrosis Patients after Allogeneic Stem Cell Transplantation

Molecular genetics may influence outcome for patients with myelofibrosis. To determine the impact of molecular genetics on outcome after allogeneic stem cell transplantation, we screened 169 patients with primary myelofibrosis (n = 110), post-ET/PV myelofibrosis (n = 46), and myelofibrosis in transformation (n = 13) for mutations in 16 frequently mutated genes. The most frequent mutation was JAK2V617F (n = 101) followed by ASXL1 (n = 49), calreticulin (n = 34), SRSF2 (n = 16), TET2 (n = 10), U2AF1 (n = 11), EZH2 (n = 7), MPL (n = 6), IDH2 (n = 5), IDH1 (n = 4), and CBL (n = 1). The cumulative incidence of non-relapse mortality (NRM) at 1 year was 21% and of relapse at 5 years 25%. The 5-year progression-free and overall survival (PFS and OS) was 52% and 56%, respectively. In a multivariate analysis CALR mutation was an independent factor for lower NRM (hazard ratio (HR) 0.415, p = 0.05), improved PFS (HR 0.393, p = 0.01), and OS (HR 0.448, p = 0.03). ASXL1 and IDH2 mutations were independent risk factors for lower PFS (HR 1.53, p = 0.008 and HR 5.451, p = 0.002, respectively), while no impact was observed for "triple negative" patients. Molecular genetics, especially CALR, IDH2, and ASXL1 mutations, may thus be useful to predict outcome independently from known clinical risk factors after allogeneic stem cell transplantation for myelofibrosis.