Tucker M A, Meadows A T, Boice J D, Stovall M, Oberlin O, Stone B J, Birch J, Voûte P A, Hoover R N, Fraumeni J F
J Natl Cancer Inst. 1987 Mar;78(3):459-64.
The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents.
晚期效应研究组的13家机构对9170名2岁及以上的儿童癌症幸存者的白血病风险进行了评估。根据一般人群发病率，22名未转诊个体发生了继发性白血病，预期为1.52例[相对风险（RR）=14；95%置信区间（CI），9-22]。通过对25例病例和90例匹配对照进行的病例对照研究，确定了首次癌症治疗对后续白血病风险的影响。使用烷化剂治疗与白血病风险显著升高相关（RR=4.8；95%CI，1.2-18.9）。通过烷化剂评分估计，白血病风险与烷化剂总剂量之间也观察到了很强的剂量反应关系。在最高剂量类别中，白血病的RR达到23。然而，放射治疗并未增加风险。尽管多柔比星也被确定为可能的风险因素，但儿童癌症治疗后白血病的额外风险几乎完全归因于烷化剂。
