Margolin K, Forman S J
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California 91010, USA.
Cancer J Sci Am. 2000 Feb;6 Suppl 1:S33-8.
The results of trials using interleukin (IL)-2-based therapy in leukemia and after hematopoietic stem cell transplant suggest that such therapy could have an impact on preventing disease relapse in patients with hematologic malignancy who achieve a minimal disease state. The use of immunotherapy in the autologous transplant setting is modeled in part on the well-characterized immunotherapeutic effect of the graft-versus-tumor response in patients undergoing allogeneic transplantation. The graft-versus-tumor response, mediated by donor cells, contributes to the higher cure rates seen in patients undergoing allogeneic transplant for the treatment of a variety of hematologic malignancies, including acute and chronic myelogenous and lymphoblastic leukemia, myeloma, and lymphoma
The literature was reviewed, and we relate our own clinical experience with IL-2 therapy in this setting.
Preclinical in vitro and animal data show a variety of leukemia cells are sensitive to autologous IL-2-activated effector cells. In addition, laboratory studies show that IL-2 can be used to activate antitumor cellular responses from bone marrow and peripheral blood without compromising hematopoiesis. Most importantly, in vitro studies show that chemoresistant malignant hematopoietic cells are sensitive to IL-2-induced cell death, thus emphasizing the lack of cross resistance to immunologic-based therapeutics. The results of phase I and II studies conducted in patients with acute myelogenous leukemia in first or subsequent remission suggest that autologous IL-2-activated cells may mediate an antitumor response and aid in preventing relapse after autologous transplantation. Clinical trials to determine the role of IL-2 after transplantation for the treatment of acute and chronic myelogenous leukemia, multiple myeloma, and lymphoma are ongoing.
These studies will help define the optimal dose and schedule of IL-2 and its role in augmenting therapeutic immune-mediated autologous responses.
在白血病及造血干细胞移植后使用基于白细胞介素（IL）-2的治疗的试验结果表明，这种治疗可能对预防达到微小疾病状态的血液系统恶性肿瘤患者的疾病复发有影响。在自体移植环境中使用免疫疗法部分是仿照在接受同种异体移植的患者中充分表征的移植物抗肿瘤反应的免疫治疗效果。由供体细胞介导的移植物抗肿瘤反应有助于接受同种异体移植治疗各种血液系统恶性肿瘤（包括急性和慢性髓性及淋巴细胞白血病、骨髓瘤和淋巴瘤）的患者获得更高的治愈率。
回顾了文献，并阐述了我们自己在这种情况下使用IL-2治疗的临床经验。
临床前的体外和动物数据表明，多种白血病细胞对自体IL-2激活的效应细胞敏感。此外，实验室研究表明，IL-2可用于激活骨髓和外周血的抗肿瘤细胞反应而不损害造血功能。最重要的是，体外研究表明，化疗耐药的恶性造血细胞对IL-2诱导的细胞死亡敏感，从而强调了对基于免疫的治疗缺乏交叉耐药性。在首次或后续缓解的急性髓性白血病患者中进行的I期和II期研究结果表明，自体IL-2激活的细胞可能介导抗肿瘤反应并有助于预防自体移植后的复发。确定移植后IL-2在治疗急性和慢性髓性白血病、多发性骨髓瘤和淋巴瘤中的作用的临床试验正在进行中。
这些研究将有助于确定IL-2的最佳剂量和给药方案及其在增强治疗性免疫介导的自体反应中的作用。
