title: PEG-IFN-alpha-2b therapy in BCR-ABL-negative myeloproliferative disorders: final result of a phase 2 study.
abstract: BACKGROUND
  Interferon-alpha (IFN-alpha) has shown significant activity in the treatment of BCR-ABL-negative myeloproliferative disorders (MPDs), particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG-IFN-alpha-2b is a pegylated IFN-alpha-2b with a significant advantage over nonpegylated form in that it is administered once a week.
  
  
  METHODS
  Thirty-eight patients with BCR-ABL-negative MPDs were treated with PEG-IFN-alpha-2b, given subcutaneously weekly, at the starting dose of 3 microg/kg/wk for the first 14 patients and then 2 microg/kg/wk for the next 24 patients, with intent to treat patients as long as they benefited from the therapy.
  
  
  RESULTS
  Median age was 54 years. Patient diagnoses were: 13 (34%) ET; 11 (29%) primary myelofibrosis (PMF); 5 (13%) BCR-ABL-negative chronic myeloid leukemia (CML); 4 (10.5%) hypereosinophilic syndrome (HES); 4 (10.5%) PV; and 1 (3%) unclassified myeloproliferative disease (uMPD). Recorded grade 3-4 toxicities were related to fatigue, myelosuppression, and musculoskeletal pain. Ten (26%) patients stopped treatment because of toxicity. Thirteen (34%) patients achieved a complete remission, and 4 (11%) achieved a partial response. Only 1 patient with PMF responded. Median time to response was 5 months. Median duration of response was 20 months. Three patients had a sustained response for >24 months.
  
  
  CONCLUSIONS
  PEG-IFN-alpha-2b, with proper dose modifications, is effective in controlling disease in a significant proportion of BCR-ABL-negative MPD patients, particularly ET and PV. However, toxicities encountered with PEG-IFN-alpha-2b therapy are similar to those obtained with conventional IFN-alpha, thus limiting the duration of therapy.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Richie
authors.forename: Miloslav
authors.initials: M
authors.lastname: Beran
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D016044:Fusion Proteins, bcr-abl; C417083:peginterferon alfa-2b