Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 23, Issue 7, Pages 1095-1101Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2017.03.034
Keywords
Myelofibrosis; Allogeneic stem cell transplantation; Molecular genetics; Calreticulin; ASXL1
Categories
Funding
- Federal Ministry of Education and Research [01EO0802]
- Deutsche Krebshilfe [110284, 110287, 110292, 111267]
- Deutsche Jose Carreras Leukamie-Stiftung [DJCLS R13/14]
- DFG [HE 5240/5-1, HE 5240/6-1]
- ERC grant under the European Union's Horizon research and innovation programme [638035]
- EHA Fellowship Award, Hamburger Krebsgesellschaft
- Dieter-Schlag-Stiftung
- European Research Council (ERC) [638035] Funding Source: European Research Council (ERC)
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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. (C) 2017 American Society for Blood and Marrow Transplantation.
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