Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971–1991)

Abstract

The ‘gold standard’ for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971–October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2–87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600 000/mm³, 79 (40%) had white blood cells >12 000 mm³; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). thereafter treatment was given according to toxicity and maintenance of response. all patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2–4) and 47 of them received pb when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to pb. during a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with pb alone and 71/199 (35.7%) patients received phlebotomies occasionally. sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). eleven (5.5%) patients developed acute myelogenous leukemia (aml) after a median time of treatment of 89 months (range 33–188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31–182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13–118 months). the cumulative risk of leukemia in pv was 2% (95% ci: 0–4%) and 6% (95% ci: 1–11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% ci: 1–5%) and 9% (95% ci: 3–15%) at 5 and 10 years, respectively. as of may 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. in conclusion, this retrospective analysis confirms the efficacy and safety of pb in pv patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of pb in the treatment of pv.