Leukemic transformation of polycythemia vera and essential thrombocythemia possibly associated with an alkylating agent.
BACKGROUND
Leukemic transformation of polycythemia vera (PV) and essential thrombocythemia (ET) is influenced by the therapeutic modalities used. A high incidence of leukemic transformation was found among patients 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.


METHODS
Twenty-seven patients with PV and 29 with ET diagnosed from January 1975 to August 1993 and whose clinical course could be followed comprised the members of this retrospective study. The patients were examined for the treatment administered, hematologic data, vascular complications, malignancies including leukemia, and eventual outcome.


RESULTS
Eighteen patients with PV and 16 with ET were treated with CQ. The follow-up was 51-209 months for patients with PV and 28-176 months for those with ET. Three patients with PV (17% of those treated with CQ) and 5 with ET (31% of those treated with CQ) had subsequent transformation to acute leukemia. The median period until transformation of patients with PV was 94 months, 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. Likewise, the median follow-ups for patients with ET with or without transformation were 130 and 90 months, respectively; the difference was insignificant. The median total days of CQ administration and the median total 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), respectively, for those without transformation. These observations suggest that CQ may be involved in the leukemic transformation of PV and ET. The subtypes of leukemia transformed from PV corresponded to M2 in two patients and to M4 in one. All five patients with ET were found to have megakaryoblastic features at transformation, and three were diagnosed as having leukemic subtype M7. Chromosomal abnormalities were found in all five patients (two PV and three ET) examined after leukemic transformation, showing multiple and complex abnormalities in four.


CONCLUSIONS
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 causal role of CQ in leukemic transformation of PV and ET is suggested.
Higuchi
T
T
Division of Hematology, Showa University Fujigaoka Hospital, Yokohama, Japan.
Okada
S
S
Mori
H
H
Niikura
H
H
Omine
M
M
Terada
H
H
D000328:Adult; D000368:Aged; D002225:Carbazilquinone / Q000009:adverse effects*; D002869:Chromosome Aberrations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000150:complications* / Q000188:drug therapy; D012189:Retrospective Studies; D013920:Thrombocythemia, Essential / Q000150:complications* / Q000188:drug therapy
D002225:Carbazilquinone