ACUTE-LEUKEMIA AFTER HYDROXYUREA THERAPY IN POLYCYTHEMIA-VERA AND ALLIED DISORDERS - PROSPECTIVE-STUDY OF EFFICACY AND LEUKAEMOGENICITY WITH THERAPEUTIC IMPLICATIONS

Fifty consecutive patients, 30 of whom had polycythaemia vera (PV), 10 essential thrombocythaemia (ET), and 10 myelofibrosis (MF), entered a long-term prospective study of hydroxyurea (HU) therapy. The indicati on for treatment was mainly thrombocytosis or symptomatic splenomegaly . Control of erythrocytosis and thrombocytosis was achieved in 70% of the patients. Continuous maintenance treatment was required. In 15% of responding patients with thrombocytosis, unexpected rises of the plat elet count occurred during maintenance therapy. Severe thrombo-embolic events occurred in 6 patients. The size of the spleen decreased in al l patients who did not develop thrombocytopenia and could absorb adequ ate HU doses. Acute leukaemia (AL) was diagnosed in 9 patients and a m yelodysplastic syndrome in one. Seven of them had been treated with HU alone. Among the patients with PV and ET, 6 developed AL and 4 of the m were treated with HU alone (3 PV and 1 ET), giving an incidence of 1 0.5%. In previously untreated patients with initially normal karyotype s (n = 19), chromosome abnormalities developed during HU therapy in 7 (37%). Our results indicate that HU should be regarded as leukaemogeni c, at least when used for treatment of PV and allied diseases. Since m yelosuppressive treatment of PV does not prolong survival, the use of HU should be restricted to patients in whom the treatment indication o utweighs the risk of leukaemia induction.