Long-term outcomes of polycythemia vera patients treated with pipobroman as initial therapy

Abstract

From 1968 to 1993, 179 newly diagnosed patients with polycythemia vera (PV) were enrolled in a prospective study using pipobroman as first chemotherapy. Among them, 140 fulfilled the Polycythemia Vera Study Group criteria for PV, and 39 patients (22%) can be considered as idiopathic erythrocytosis (IE). Vascular events occurred in 10% of IE and 20% of PV patients and solid tumors in 7.7% of IE and 12.8% of PV patients. There were no differences between PV and IE patients with regard to progression to myelofibrosis (MF), leukemic events and overall survival. Overall, 98.3% of patients initially responded to pipobroman, with very mild toxicity. A total of 164 PV patients who received more than 1 year of pipobroman were analyzed for long-term evolution. The actuarial risk of thrombosis was 15.6 and 23.8% at 10 and 18 years, respectively. In all, 21 patients developed a solid tumor during follow-up, added and/or switched drugs being a risk factor. Actuarial risk of MF was as low as 4.9 and 9.4% at 10 and 15 years, respectively. Actuarial risk of leukemia was 14.4 and 18.7% at 10 and 15 years, respectively. Hyperleukocytosis at diagnosis was the only variable significantly associated with higher risk of leukemia. The median survival was 15.5 years, with two initial adverse prognostic factors: age above 60 years and hyperleukocytosis. Despite an increasing risk of leukemia with time, survival was not lower when compared to the French matched population. Only age and hyperleukocytosis at diagnosis were found to have a prognostic value in PV.

A retrospective study on 226 polycythemia vera patients: impact of median hematocrit value on clinical outcomes and survival improvement with anti-thrombotic prophylaxis and non-alkylating drugs

“…In spite of these unfavorable prognostic features, the overall survival (91% at the median follow-up time of 5.84 years) compares favorably to that reported in many other studies [3][4][5][6]. Although we did not perform a prospective, randomized study and the median follow-up is shorter than 10 years, the wide use in our patients of lowdose ASA and the strong limitation of alkylating cytotoxic therapy may have contributed to this more favorable outcome and to an incidence of leukemic transformation in the lowest range of values reported in literature [4,[6][7][8]. Indeed, a French randomized study with very long followup has recently demonstrated a lower incidence of leukemic evolution and improved survival with the use of hydroxyurea compared to pipobroman [32].…”

“…Polycythemia vera (PV) is the most common chronic myeloproliferative neoplasm, with an annual incidence of 2.3 per 100,000 [1,2], a reported median survival of 10-15 years [3][4][5][6] and an overall mortality of 3.5 per 100 person/year [5]. Thrombotic complications are the main cause of morbidity and mortality, occurring in more than one third of patients and causing 35-45% of deaths [5,6].…”

“…Thrombotic complications are the main cause of morbidity and mortality, occurring in more than one third of patients and causing 35-45% of deaths [5,6]. Other possible adverse events are the evolution into secondary myelofibrosis (MF) or acute myeloid leukemia (AML) occurring in 10-15% [4,[6][7][8] and 2-15% [4,[8][9][10][11][12][13][14][15][16] of patients, respectively, depending on treatments and with increased incidence with long-standing disease.…”

Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders

“…[15][16][17][18]20,48,49 A study on 831 patients with PV and ET followed for a median time of about 10 years provided evidence that life expectancy of PV patients is reduced when compared with that of the general population, whereas the survival of patients with ET is not significantly shortened. 18 A study from Mayo Clinic including 322 patients with ET followed for a median time of 13.6 years confirmed these data on survival in the first decade of disease and showed that survival became significantly worse thereafter.…”

“…With regard to the survival, PMF is associated with a substantial reduction in life expectancy, [6][7][8][9][10][11][12][13][14] and ET affects more the patients' quality of life than their survival, whereas PV is associated with both a substantial morbidity and a certain reduction in the patients' life expectancy. [15][16][17][18] Because of this, prognostic studies in the MPDs have been carried out primarily in PMF. In the last years, however, attention is increasingly being paid to the identification of prognostic factors in ET and PV, primarily focused on the risk of thrombosis.…”