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

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.