title: Long term molecular responses in a cohort of Danish patients with essential thrombocythemia, polycythemia vera and myelofibrosis treated with recombinant interferon alpha.
abstract: Within recent years data has accumulated demonstrating the efficacy of recombinant interferon alpha2 (rIFN-alpha2) in the treatment of chronic myeloproliferative neoplasms (MPNs). We report on clinical and molecular data in the largest cohort of JAK2 V617F mutant MPN Danish patients (n=102) being treated long-term with rIFN-alpha2 (rIFN-alpha2a and rIFN-alpha2b in a non-clinical trial setting. The median follow-up was 42 months. We substantiate the capacity of rIFN-alpha2 to induce complete hematologic remissions (ET 95%, PV 68%) and molecular response. In total 76 patients (74.5%) had a decline in JAK2 V617F allele burden with a median reduction from baseline of 59% (95% c.i. 50-73%, range 3-99%). A decline in JAK2 V617F allele burden was recorded in both ET (median 24-10% (95% c.i.: 8-16%), and PV (median 59-35% (95% c.i.: 17-33%). Patients with the lowest pre-treatment JAK2 V617F allele burdens tend to achieve the most favourable responses on long term treatment with rIFN-alpha2. Eleven patients (10%) had deep molecular remissions with ≤ 2% JAK2 V617F mutant DNA. Finally, long term treatment with rIFN-alpha2 was associated with a very low thrombosis rate. Our observations are supportive of the concept of early up-front treatment with rIFN-alpha2.
authors.affiliation: Department of Hematology, Odense University Hospital, Denmark. thomas.stauffer.larsen@rsyd.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Stauffer Larsen
authors.forename: Katrine F
authors.initials: KF
authors.lastname: Iversen
authors.forename: Esben
authors.initials: E
authors.lastname: Hansen
authors.forename: Anders Bruun
authors.initials: AB
authors.lastname: Mathiasen
authors.forename: Claus
authors.initials: C
authors.lastname: Marcher
authors.forename: Mikael
authors.initials: M
authors.lastname: Frederiksen
authors.forename: Herdis
authors.initials: H
authors.lastname: Larsen
authors.forename: Inge
authors.initials: I
authors.lastname: Helleberg
authors.forename: Caroline Hasselbalch
authors.initials: CH
authors.lastname: Riley
authors.forename: Ole W
authors.initials: OW
authors.lastname: Bjerrum
authors.forename: Dorthe
authors.initials: D
authors.lastname: Rønnov-Jessen
authors.forename: Michael Boe
authors.initials: MB
authors.lastname: Møller
authors.forename: Karin
authors.initials: K
authors.lastname: de Stricker
authors.forename: Hanne
authors.initials: H
authors.lastname: Vestergaard
authors.forename: Hans Carl
authors.initials: HC
authors.lastname: Hasselbalch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003718:Denmark; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000235:genetics; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D012189:Retrospective Studies; D013920:Thrombocythemia, Essential / Q000188:drug therapy* / Q000235:genetics; D013997:Time Factors; D055815:Young Adult
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Interferon; JAK2; Molecular; Myeloproliferative