Efficacy of pipobroman in the treatment of polycythemia vera: long-term results in 163 patients

Abstract

BACKGROUND AND OBJECTIVES. Polycythemia vera (PV) is a myeloproliferative disorder, characterized by the expansion of the red cell mass. Our purpose was to evaluate the efficacy of pipobroman (PB) in the long-term control of PV and to assess early and late events. DESIGN AND METHODS. From June 1975 to December 1997, 163 untreated patients with PV (median age 57 years, range 30-82) were treated with PB in a single Institute for a median follow-up of 120 months. The diagnosis was made according to the Polycythemia Vera Study Group criteria. PB was given at the dose of 1 mg/kg/day until hematologic response (hematocrit < 45% and platelets < 400x109/L) and of 0.3-0.6 mg/kg/day as maintenance therapy. RESULTS. Hematologic remission was achieved in 94% of patients in a median time of 13 weeks (range 6-48). Median overall survival was 215 months, with a standardized mortality ratio of 1.7. The cumulative risk of death was 11%, 22%, and 26% at 7, 10, and 12 years, respectively. The incidence of thrombotic events was 18.4x105 person-year and the cumulative risk was 6%, 11%, 16%, and 20% at 3, 7, 10, and 12 years respectively. Acute leukemia occurred in 11 patients, myelofibrosis in 7, and solid tumors in 11. The 10-year cumulative risk of leukemia, myelofibrosis, and solid tumors was 5%, 4%, and 8%, respectively. In the logistic analysis age over 65 (p = 0.0001) and thrombotic events at diagnosis (p = 0.001) were significantly correlated with a higher risk of death. Female gender (p = 0.02) and age over 65 (p = 0.01) significantly influenced the occurrence of thrombotic complications. Age was the only significant risk factor for leukemia (p = 0.04) and for solid tumors (p = 0.03), while the duration of PB treatment did not influence these risks. No significant risk factor was demonstrated for myelofibrosis. INTERPRETATION AND CONCLUSIONS. This study demonstrates in a large series of patients, observed for a long period, that pipobroman is effective in the long-term control of PV. The risk of early thrombotic complications at 3 years is 6% and the 10-year risk of acute leukemia, late myelofibrosis, and solid tumors is 5%, 4%, and 8%, respectively. The duration of pipobroman treatment did not correlate with these events.