Löfvenberg E, Nordenson I, Wahlin A
Department of Medicine, University Hospital, Umeå, Sweden.
Cancer Genet Cytogenet. 1990 Oct 1;49(1):57-67. doi: 10.1016/0165-4608(90)90164-6.
Eighty-one consecutive hydroxyurea-treated patients with Philadelphia (Ph) chromosome negative chronic myeloproliferative disease were followed prospectively from 1981 to 1989; 35 of them had polycythemia vera, 32 had essential thrombocythemia, 12 had myelofibrosis, and 2 had myeloproliferative syndromes. The 81 patients were treated with hydroxyurea for a total of 3,804 months during the observation time. Only three patients had been treated with alkylating agents or 32P before start of hydroxyurea treatment. Four patients transformed into acute myeloid leukemia or myelodysplastic syndromes; three of these patients had essential thrombocythemia, and one had a myeloproliferative syndrome. Two patients died of solid cancers. Five out of 53 evaluable patients (9%) had pretreatment clonal cytogenetic abnormalities involving chromosomes 1, 9, 20, and 21. At follow-up, during or after hydroxyurea treatment, 15% had cytogenetic abnormalities, an unexpectedly low frequency compared to the previously reported frequency in patients with polycythemia vera treated with alkylating agents. None of our patients who developed cytogenetic clonal changes during hydroxyurea therapy had polycythemia vera. However, follow-up is too short to draw any conclusions about the mutagenic potential of hydroxyurea compared to alkylating agents.
1981年至1989年，对81例连续接受羟基脲治疗的费城（Ph）染色体阴性慢性骨髓增殖性疾病患者进行了前瞻性随访；其中35例患有真性红细胞增多症，32例患有原发性血小板增多症，12例患有骨髓纤维化，2例患有骨髓增殖综合征。在观察期间，81例患者接受羟基脲治疗的总时长为3804个月。只有3例患者在开始羟基脲治疗前接受过烷化剂或32P治疗。4例患者转化为急性髓系白血病或骨髓增生异常综合征；其中3例患有原发性血小板增多症，1例患有骨髓增殖综合征。2例患者死于实体癌。53例可评估患者中有5例（9%）在治疗前存在涉及1号、9号、20号和21号染色体的克隆性细胞遗传学异常。在随访期间，即羟基脲治疗期间或之后，15%的患者出现细胞遗传学异常，与先前报道的接受烷化剂治疗的真性红细胞增多症患者的频率相比，这一频率出乎意料地低。在羟基脲治疗期间出现细胞遗传学克隆性改变的患者中，没有一例患有真性红细胞增多症。然而，随访时间过短，无法就羟基脲与烷化剂相比的致突变潜力得出任何结论。
