Higuchi T, Okada S, Mori H, Niikura H, Omine M, Terada H
Division of Hematology, Showa University Fujigaoka Hospital, Yokohama, Japan.
Cancer. 1995 Jan 15;75(2):471-7. doi: 10.1002/1097-0142(19950115)75:2<471::aid-cncr2820750210>3.0.co;2-b.
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.
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.
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.
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.
真性红细胞增多症（PV）和原发性血小板增多症（ET）的白血病转化受所用治疗方式的影响。在用烷化剂卡波醌（CQ）治疗的PV或ET患者中，发现白血病转化的发生率很高。本研究旨在评估CQ与PV和ET的白血病转化之间的因果关系。
本回顾性研究的对象包括1975年1月至1993年8月诊断出的27例PV患者和29例ET患者，其临床病程可被追踪。对患者进行了治疗情况、血液学数据、血管并发症、包括白血病在内的恶性肿瘤以及最终结局的检查。
18例PV患者和16例ET患者接受了CQ治疗。PV患者的随访时间为51 - 209个月，ET患者为28 - 176个月。3例PV患者（占接受CQ治疗者的17%）和5例ET患者（占接受CQ治疗者的31%）随后转化为急性白血病。PV患者转化前的中位时间为94个月，而未转化患者的中位随访时间为146个月（P < 0.01）。转化患者的CQ给药总天数中位数和CQ总剂量中位数分别为2022天和1226毫克，未转化患者分别为1051天（P < 0.05）和435毫克（P < 0.01）。同样，ET转化患者和未转化患者的中位随访时间分别为130个月和90个月；差异不显著。转化患者的CQ给药总天数中位数和CQ总剂量中位数分别为2075天和1019毫克，未转化患者分别为571天（P < 0.05）和231毫克（P < 0.01）。这些观察结果表明，CQ可能与PV和ET的白血病转化有关。PV转化而来的白血病亚型，2例为M2型，1例为M4型。所有5例ET转化患者在转化时均具有巨核母细胞特征，3例被诊断为白血病M7亚型。白血病转化后检查的所有5例患者（2例PV和3例ET）均发现染色体异常，4例显示出多重和复杂异常。
本研究表明，PV或ET疾病随后转化为白血病的患者，其CQ给药总天数和CQ总剂量均更大，提示CQ在PV和ET的白血病转化中可能起因果作用。
