Fairley G H
Arch Intern Med. 1976 Dec;136(12):1406-12.
Now that it has been clearly established that tumor-associated antigens exist in acute leukemia in man, as in animals, the possibility of stimulating the patient's immune system to react against them arises. In animal experiments the most effective method of influencing the progress of leukemia after the implantation of living malignant cells has been a combination of nonspecific stimulation of the reticuloendothelial system, with agents such as BCG or Corynebacterium parvum, either with chemotherapy or with specific immunization with irradiated leukemic cells. However, such treatment is only effective if the number of living malignant cells is small as it takes a powerful immune response to overcome even a small number of malignant cells. It is for these reasons that most of the studies in man have been on patients with acute leukemia in remission. Mathé, in 1969, produced evidence that BCG and irradiated allogenic leukemia cells could lengthen the duration of remission in ALL in children. However, later results of intensive combination chemotherapy, together with prophylactic treatment of the central nervous system by Pinkel and his colleagues, were so encouraging that immunotherapy is not felt to be needed and therefore is not being extensively used in this form of leukemia at the moment. The situation in AML, particularly in adults, is completely different. The maintenance of remission with chemotherapy in this type of leukemia is difficult and relapses occur quite rapidly. Various centers have now shown that both remission lengths and overall survival are significantly prolonged by using BCG with or without irradiated allogenic leukemia cells.
既然已经明确证实,如同在动物身上一样,人类急性白血病中存在肿瘤相关抗原,那么就产生了刺激患者免疫系统对其作出反应的可能性。在动物实验中,植入活的恶性细胞后影响白血病进展的最有效方法,是用卡介苗或短小棒状杆菌等制剂对网状内皮系统进行非特异性刺激,联合化疗或用经照射的白血病细胞进行特异性免疫。然而,只有在活的恶性细胞数量较少时,这种治疗才有效,因为即使要克服少量恶性细胞也需要强大的免疫反应。正是由于这些原因,大多数针对人类的研究都是针对处于缓解期的急性白血病患者。1969年,马泰提出证据表明,卡介苗和经照射的同种异体白血病细胞可以延长儿童急性淋巴细胞白血病的缓解期。然而,后来平克尔及其同事进行的强化联合化疗以及中枢神经系统预防性治疗的结果非常令人鼓舞,以至于人们认为不需要免疫疗法,因此目前这种疗法在这种白血病中并未得到广泛应用。急性髓细胞白血病的情况,尤其是在成年人中,完全不同。用化疗维持这种类型白血病的缓解很困难,而且复发很快。现在各个中心都表明,使用卡介苗联合或不联合经照射的同种异体白血病细胞,缓解期长度和总生存期都能显著延长。