Haas J F, Kittelmann B, Mehnert W H, Staneczek W, Möhner M, Kaldor J M, Day N E
Br J Cancer. 1987 Feb;55(2):213-8. doi: 10.1038/bjc.1987.40.
A case-control study was conducted to determine whether the development of leukaemia was associated with chemotherapy for neoplasms of the ovary or breast, in a population where most such chemotherapy consisted of cyclophosphamide alone. Cases and controls were identified from the National Cancer Registry of the German Democratic Republic. Cases were women who had developed leukaemia as a second primary after an initial diagnosis, at least one year before, of an ovarian or breast tumour. Controls were patients with an ovarian tumour or breast cancer who had survived to the year when the case developed a leukaemia but who had not themselves developed a second malignancy. Controls were matched to cases by the site of the first primary and its year of diagnosis, as well as year of birth. The relative risk for acute leukaemia following treatment with cyclophosphamide alone was significantly elevated (P less than 0.05), at 14.6 for ovarian tumour patients and 2.7 for breast cancer patients. Among breast cancer patients the increased risk of leukaemia associated with chemotherapy was confined to women who had been under 50 years of age at the time of diagnosis of the breast cancer (for whom the relative risk was 13.1). No excess risk of leukaemia was observed in association with radiotherapy for either ovarian or breast cancer patients. The present findings strongly suggest that cyclophosphamide as a single chemotherapeutic agent is capable of inducing leukaemia in humans.
开展了一项病例对照研究，以确定在大多数此类化疗仅包含环磷酰胺的人群中，白血病的发生是否与卵巢或乳腺癌的化疗相关。病例和对照均来自德意志民主共和国国家癌症登记处。病例为在初次诊断卵巢或乳腺肿瘤至少一年后发生白血病作为第二原发性肿瘤的女性。对照为患有卵巢肿瘤或乳腺癌且存活至病例发生白血病年份但未发生第二种恶性肿瘤的患者。对照按首次原发性肿瘤的部位及其诊断年份以及出生年份与病例进行匹配。单独使用环磷酰胺治疗后急性白血病的相对风险显著升高（P小于0.05），卵巢肿瘤患者为14.6，乳腺癌患者为2.7。在乳腺癌患者中，与化疗相关的白血病风险增加仅限于乳腺癌诊断时年龄在50岁以下的女性（其相对风险为13.1）。未观察到卵巢癌或乳腺癌患者放疗与白血病的额外风险相关。目前的研究结果强烈表明，环磷酰胺作为单一化疗药物能够在人类中诱发白血病。
