Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2017
Impact of Molecular Genetics on Outcome in Myelofibrosis Patients after Allogeneic Stem Cell Transplantation.
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Kröger Nicolaus, Panagiota Victoria, Badbaran Anita, Zabelina Tatjana, Triviai Ioanna, Araujo Cruz Michelle Maria, Shahswar Rabia, Ayuk Francis, Gehlhaar Marten, Wolschke Christine, Bollin Robin, Walter Carolin, Dugas Martin, Wiehlmann Lutz, Lehmann Ulrich, Koenecke Christian, Chaturvedi Anuhar, Alchalby Haefaa, Stadler Michael, Eder Matthias, Christopeit Max, Göhring Gudrun, Koenigsmann Michael, Schlegelberger Brigitte, Kreipe Hans-Heinrich, Ganser Arnold, Stocking Carol, Fehse Boris, Thol Felicitas, Heuser Michael
Аннотация
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-essential thrombocythemia/polycythemia vera 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 nonrelapse mortality (NRM) at 1 year was 21% and of relapse at 5 years 25%. The 5-year rates progression-free (PFS) and overall survival (OS) were and 56%, respectively. In a multivariate analysis CALR mutation was an independent factor for lower NRM (HR, .415; P = .05), improved PFS (HR, .393; P = .01), and OS (HR, .448; P = .03). ASXL1 and IDH2 mutations were independent risk factors for lower PFS (HR, 1.53 [P = .008], and HR, 5.451 [P = .002], respectively), whereas 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.