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

Background and Objectives. Polycythemia vera (PV) is a myeloproliferative d isorder characterized by the expansion of the red cell mass. Our purpose wa s to evaluate the efficacy of pipobroman (PB) in the long-term control of P V 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 singl e Institute for a median follow-up of 120 months, The diagnosis was made ac cording to the Poly: cythemia Vera Study Group criteria. PB was given at th e dose of 1 mg/kg/day until hematologic response (hematocrit <45% and plate lets < 400x10(9)/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 thro mbotic events was 18.4x10(5) person-years and the cumulative risk was 6%, 1 1%, 16%, and 20% at 3, 7, 10, and 12 years respectively. Acute leukemia occ urred in 11 patients, myelofibrosis in 7, and solid tumors in 11. The 10-ye ar cumulative risk of leukemia, myelofibrosis, and solid tumors was 5%, 4%, and,8%, respectively. In the logistic analysis age over 65 (p = 0.0001) an d 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 so lid 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 o f patients, observed for a long period, that pipobroman is effective in the longterm control of PV. The risk of early thrombotic complications at 3 ye ars is 6% and the 10-year risk of acute leukemia, late myelofibrosis, and s olid tumors is 5%, 4%, and 8%, respectively. The duration of pipobroman tre atment did not correlate with these events. (C)2000, Ferrata Storti Foundat ion.