Pilot study of pegylated interferon-alpha 2b in patients with essential thrombocythemia.
OBJECTIVE
Interferon-alpha (IFN-alpha) has been shown to control symptoms, reduce platelet counts, and reduce the bone marrow megakaryocyte mass in patients with essential thrombocythemia (ET). A semisynthetic protein-polymer conjugate of IFN-alpha 2b (PEG-IFN2b) increases the serum half-life of IFN-alpha 2b. We conducted a pilot study of Peg-IFN2b in patients with ET.


METHODS
Patients with a history of persistent (greater than 2 months) platelet counts >600 x 10(9)/l, with hyperplasia of bone marrow megakaryocytes in the absence of an alternate identifiable cause of thrombocytosis were eligible. Patients were required to have either thrombohemorrhagic signs and/or symptoms if previously untreated; persistence of thrombohemorrhagic signs and/or symptoms if receiving anagrelide, IFN-alpha, or hydroxyurea; or intolerance to anagrelide, IFN-alpha, or hydroxyurea. The initial PEG-IFN2b dose was from 1.5 to 4.5 micro g/kg per week subcutaneously with subsequent dose adjustments as indicated by response and adverse events.


RESULTS
Eleven patients (nine female, median age 54 years, range 26-69 years) were treated. PEG-IFN2b rapidly controlled platelet counts and resolved symptoms in all patients. The median duration of PEG-IFN2b therapy on-study was 9 months (range 4-17 months). No patient had signs or symptoms of thrombosis or hemorrhage while on study. After 2 months of therapy, 10 patients (91%) were in complete remission, and 11 (100%) after 4 months. One patient discontinued therapy at 4 months because of persistent grade 3 fatigue and a second at 5 months because of anxiety and depression.


CONCLUSIONS
PEG-IFN2b has significant activity in patients with ET. Long-term follow-up of a larger cohort of patients is needed to define its role in this disease.
Alvarado
Yesid
Y
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030, USA.
Cortes
Jorge
J
Verstovsek
Srdan
S
Thomas
Deborah
D
Faderl
Stephan
S
Estrov
Zeev
Z
Kantarjian
Hagop
H
Giles
Francis J
FJ
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010976:Platelet Count; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D013922:Thrombocytosis / Q000097:blood / Q000188:drug therapy*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a