Delbrück H, Schaison G, Chelloul N, Bernard J
Dtsch Med Wochenschr. 1975 Sep 5;100(36):1792-7. doi: 10.1055/s-0028-1106462.
A malignant hepatoma occurred in a 12-year-old girl who eight years previously had developed an acute lymphoblastic leukaemia which for eight years had been in complete haematological remission. Fourteen months after the last re-induction treatment period had been discontinued, but while on methotrexate and 6-mercaptopurine maintenance, a hepatocellular liver carcinoma developed of which the patient died after a fulminating course, still in complete haematological remission. As far as is known, no direct carcinogenic effect can be ascribed to the two antimetabolites, but it must be assumed that these two drugs, taken by the patient for over seven years, led to cirrhosis of the liver whose malignant transformation was significantly influenced by the immunosuppressive effects of methotrexate and 6-mercaptopurine, given as maintenance therapy according to protocol 02 LA 64, Paris.
一名12岁女孩患了恶性肝癌,该女孩8年前曾患急性淋巴细胞白血病,8年来一直处于完全血液学缓解状态。在最后一个再诱导治疗期结束停药14个月后,虽然当时正在接受甲氨蝶呤和6-巯基嘌呤维持治疗,但仍发生了肝细胞肝癌,患者在经历暴发性病程后死亡,当时仍处于完全血液学缓解状态。据了解,这两种抗代谢药物尚无直接致癌作用,但必须假定,该患者服用这两种药物超过7年,导致了肝硬化,而根据巴黎02 LA 64方案进行维持治疗时,甲氨蝶呤和6-巯基嘌呤的免疫抑制作用对其恶性转化产生了显著影响。