EPIPODOPHYLLOTOXINS, ALKYLATING-AGENTS, AND RADIATION AND RISK OF SECONDARY LEUKEMIA AFTER CHILDHOOD-CANCER
EPIPODOPHYLLOTOXINS, ALKYLATING-AGENTS, AND RADIATION AND RISK OF SECONDARY LEUKEMIA AFTER CHILDHOOD-CANCER
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DOI：
10.1136/bmj.304.6832.951
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发表时间：
1992-04-11
影响因子：
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通讯作者：
CHESSELLS, JM
中科院分区：
文献类型：
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作者：
HAWKINS, MM;WILSON, LMK;CHESSELLS, JM
目的：了解英国儿童癌症后继发性白血病的发病率及病因。设计-队列研究和病例-对照研究。背景-英国和人口为基础的儿童肿瘤国家登记。研究对象：英国1962年至1983年间诊断出的16422例儿童癌症一年存活者，其中22例为继发性白血病。1940年至1983年间，在英国诊断为儿童癌症的幸存者中观察到26例继发性白血病的病例对照研究；对照者按性别、首次患癌类型、首次患癌年龄和继发性白血病诊断间隔进行匹配。主要观察指标-患者活性骨髓的平均辐射剂量和原发肿瘤给予的表观藻毒素、烷基化剂、长春花生物碱、抗代谢物和抗生素的总累积剂量（mg/m2）。结果：除了1.4%的非霍奇金淋巴瘤患者发生继发性白血病外，该队列中继发性白血病的累积风险在最初的5年生存率超过1年的时间内未超过0.5%。在20世纪80年代早期，非霍奇金淋巴瘤患者的相应数字为4%。继发性白血病的相对风险随着暴露于鬼臼毒素和患者活性骨髓平均辐射剂量的增加而显著增加。10例患者在使用了鬼臼毒素-天冬苷9例，依托泊苷1例后发生白血病。涉及11q23的染色体易位被观察到与总共六例继发性白血病中的两例有关，其中在给药后有成功的细胞遗传学研究。结论：儿童癌症后继发性白血病可能与表臼毒素单独作用或与烷基化剂或辐射共同作用有关。
Objective-To investigate the incidence and aetiology of secondary leukaemia after childhood cancer in Britain.Design-Cohort study and a case-control study.Setting-Britain and population based National Register of Childhood Tumours.Subjects-Cohort of 16 422 one year survivors of childhood cancer diagnosed in Britain between 1962 and 1983, among whom 22 secondary leukaemias were observed. A case-control study of 26 secondary leukaemias observed among survivors of childhood cancer diagnosed in Britain between 1940 and 1983; % controls were selected matched for sex, type of first cancer, age at first cancer, and interval to diagnosis of secondary leukaemia.Main outcome measures-Dose of radiation averaged over patients' active bone marrow and total accumulated dose of epipodophyllotoxins, alkylating agents, vinca alkaloids, antimetabolites, and antibiotics (mg/m2) given for the original cancer.Results-Cumulative risk of secondary leukaemia within the cohort did not exceed 0.5% over the initial five years beyond one year survival, except that after non-Hodgkin's lymphomas 1.4% of patients developed secondary leukaemia. Corresponding figure for patients treated for non-Hodgkin's lymphomas in the early 1980s was 4%. The relative risk of secondary leukaemia increased significantly with exposure to epipodophyllotoxins and dose of radiation averaged over patients' active bone marrow. Ten patients developed leukaemia after having an epipodophyllotoxin-teniposide in nine cases, etoposide in one. Chromosomal translocations involving 11q23 were observed relating to two secondary leukaemias from a total of six for which there were successful cytogenetic studies after administration of an epipodophyllotoxin.Conclusions-Epipodophyllotoxins acting alone or together with alkylating agents or radiation seem to be involved in secondary leukaemia after childhood cancer.