PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
Authors: Swarna Mehrotra; Bhumika Sharma; Sonali Joshi; Barbara Kroczynska; Beata Majchrzak; Brady L Stein; Brandon McMahon; Jessica K Altman; Jonathan D Licht; Darren P Baker; Elizabeth A Eklund; Amittha Wickrema; Amit Verma; Eleanor N Fish; Leonidas C Platanias Journal: J Biol Chem Date: 2013-06-28 Impact factor: 5.157
Authors: Heinz Gisslinger; Oleh Zagrijtschuk; Veronika Buxhofer-Ausch; Josef Thaler; Ernst Schloegl; Guenther A Gastl; Dominik Wolf; Robert Kralovics; Bettina Gisslinger; Karin Strecker; Alexander Egle; Thomas Melchardt; Sonja Burgstaller; Ella Willenbacher; Martin Schalling; Nicole C Them; Pavla Kadlecova; Christoph Klade; Richard Greil Journal: Blood Date: 2015-08-10 Impact factor: 22.113
Authors: Jan Philipp Bewersdorf; Smith Giri; Rong Wang; Nikolai Podoltsev; Robert T Williams; Martin S Tallman; Raajit K Rampal; Amer M Zeidan; Maximilian Stahl Journal: Leukemia Date: 2020-09-01 Impact factor: 11.528