Treatment of polycythemia vera with hydroxyurea

Abstract

Conventional treatment of polycythemia vera (PV) with radioactive phosphorus or alkylating agents is associated with a significant excess of acute leukemia and cancer of the gastrointestinal tract and skin. There is thus a need for a nonmutagenic agent in the treatment of this disorder. Hydroxyurea (HU) was administered to 118 patients with a loading dose of 30 mg/kg/day for 1 week, which was then reduced to 15 mg/kg/day. Initial control of the elevated hematocrit and platelet count was achieved within 12 weeks in over 80% of patients. Long-term disease control was defined and the accumulative 1-year failure-free survival was 73% in the previously untreated patients and 59% in those patients previously treated with other myelosuppressive modalities. The HU was well tolerated and cytopenia, which generally occurred within the first 8 weeks of therapy, was transient and of little clinical significance. However, it is recommended because of this toxicity that HU be administered initially at a dose of 15-20 mg/kg/day. Three patients developed acute leukemia; two were untreated and one had had myelosuppressive therapy. Hydroxyurea is an effective agent in the treatment of PV, but continued assessment of its mutagenic potential is necessary.

Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan

“…In PV patients treated with HU alone, the incidence of AML has been reported to be about 1-3% in two larger studies each encompassing about 100 patients who have been followed over a median of 5 years [1,6]. Two more recent PV studies have documented a much higher incidence of AML after treatment with HU when the patients are followed for longer periods (5.9% at 8.5 years and 8% at 12 years, respectively) [31,32].…”

“…In patients with PV who have been treated with HU alone, the risk of transformation is reported to be between 1% [1] and 8% [31]. In patients with ET, the risk of transformation to AL has been reported on average 5% after being treated with HU.…”

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

“…[14][15][16] The long median overall survival observed could be related to the low incidence of high-risk thrombosis, reflecting a peculiar effect of this drug on thrombopoiesis as suggested by other authors. 6 The incidence of acute leukemia is lower than that observed after 32P or chlorambucil treatment 1 and not higher than that observed after hydroxyurea treatment: 17,18 therefore, prospective, collaborative and randomized clinical trials are needed to assess the role of these two myelosuppressive drugs on the outcome of PV patients.…”

“…[14][15][16] The results of PVSG Protocol-08 indicated that HU supplemented by occasional phlebotomy was able to decrease the incidence of life-threatening thrombosis when compared with historical phlebotomized patients (13.7 vs 38.1%). In addition, during the first 378 weeks of the study, acute leukemia appeared only in two HU-treated patients (3.9%), leading the authors to conclude that this drug had to be considered the drug of choice, particularly in younger patients previously untreated by myelosuppressive therapy.…”

Polycythemia Vera era 1939-1998 from Berkeley to Rotterdam and Change of PVSG into ECP Criteria of Myeloproliferative Disorders ET, PV and PMGM: Proceedings of the First Rotterdam MPD Workshop 1998 and beyond

“…As far as I can derive from the issue in Seminars of Hematology in January 1997 [42], there is no residual activity of the PVSG and all PVSG protocols are closed many years ago [11,43]. We have discussed and learned much from the results of the PVSG studies at the various meetings of the EWG.MPD since 1994 summarized in The Chronic Myeloproliferative Disorders CMPD): Essential Thrombocythemia, Polycythemia Vera and Megakaryocytic Myeloid Metaplasia.…”