LEUKEMIC TRANSFORMATION OF POLYCYTHEMIA-VERA AND ESSENTIAL THROMBOCYTHEMIA POSSIBLY ASSOCIATED WITH AN ALKYLATING AGENT

Background. Leukemic transformation of polycythemia vera (PV) and esse ntial thrombocythemia (ET) is influenced by the therapeutic modalities used. A high incidence of leukemic transformation was found among pat ients with PV or ET treated with an alkylating agent, carboquone (CQ). The study was conducted to assess the causal relationship between CQ and leukemic transformation of PV and ET. Method. Twenty-seven patient s with PV and 29 with ET diagnosed from January 1975 to August 1993 an d whose clinical course could be followed comprised the members of thi s retrospective study. The patients were examined for the treatment ad ministered, hematologic data, vascular complications, malignancies inc luding leukemia, and eventual outcome. Results. Eighteen patients with PV and 16 with ET were treated with CQ. The follow-up was 51-209 mont hs for patients with PV and 28-176 months for those with ET. Three pat ients with PV (17% of those treated with CQ) and 5 with ET (31% of tho se treated with CQ) had subsequent transformation to acute leukemia. T he median period until transformation of patients with PV was 94 month s, whereas the median follow-up of patients without transformation was 146 months (P < 0.01). The median total days of CQ administration and the median total dose of CQ were 2022 days and 1226 mg, respectively, for the patients with transformation and 1051 days (P < 0.05) and 435 mg (P < 0.01), respectively, for those without transformation. Likewi se, the median follow-ups for patients with ET with or without transfo rmation were 130 and 90 months, respectively; the difference was insig nificant. The median total days of CQ administration and the median to tal dose of CQ were 2075 days and 1019 mg, respectively, for patients with transformation and 571 days (P < 0.05) and 231 mg (P < 0.01), res pectively, for those without transformation. These observations sugges t that CQ may be involved in the leukemic transformation of PV and ET. The subtypes of leukemia transformed from PV corresponded to M2 in tw o patients and to M4 in one. All five patients with ET were found to h ave megakaryoblastic features at transformation, and three were diagno sed as having leukemic subtype M7. Chromosomal abnormalities were foun d in all five patients (two PV and three ET) examined after leukemic t ransformation, showing multiple and complex abnormalities in four. Con clusion. Showing that both the total days of CQ administration and the total dose of CQ were larger for patients with PV or ET whose disease subsequently transformed to leukemia, with this study, a possible cau sal role of CQ in leukemic transformation of PV and ET is suggested.