title: Impact of Molecular Genetics on Outcome in Myelofibrosis Patients after Allogeneic Stem Cell Transplantation.
abstract: 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.
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany. Electronic address: nkroeger@uke.uni-hamburg.de.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Panagiota
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Badbaran
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Triviai
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Michelle Maria
authors.initials: MM
authors.lastname: Araujo Cruz
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Rabia
authors.initials: R
authors.lastname: Shahswar
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Marten
authors.initials: M
authors.lastname: Gehlhaar
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Bollin
authors.affiliation: Clinical Research Group, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hanover, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Walter
authors.affiliation: Institute of Medical Informatics, Münster University, Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dugas
authors.affiliation: Clinical Research Group, Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hanover, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Wiehlmann
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Lehmann
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Koenecke
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Anuhar
authors.initials: A
authors.lastname: Chaturvedi
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Haefaa
authors.initials: H
authors.lastname: Alchalby
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Christopeit
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Göhring
authors.affiliation: Outpatient Oncology Center Hannover, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Koenigsmann
authors.affiliation: Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Kreipe
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Carol
authors.initials: C
authors.lastname: Stocking
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg, Eppendorf, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Fehse
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology / Q000379:methods*; D055728:Primary Myelofibrosis / Q000235:genetics*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods*; D055815:Young Adult
keywords: ASXL1; Allogeneic stem cell transplantation; Calreticulin; Molecular genetics; Myelofibrosis