Kragel A H, Travis W D, Feinberg L, Pittaluga S, Striker L M, Roberts W C, Lotze M T, Yang J J, Rosenberg S A
Pathology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Hum Pathol. 1990 May;21(5):493-502. doi: 10.1016/0046-8177(90)90005-p.
The use of interleukin-2 (IL-2), either alone or in combination with lymphokine-activated killer cells, tumor infiltrating lymphocytes, or other immunotherapeutic agents has added a new list of alternatives to conventional antineoplastic regimens. Little information is available about the pathologic changes occurring in patients treated with these agents. In this study, we reviewed the necropsy materials from 19 patients, 12 men and 7 women, with a variety of malignancies including melanoma, renal cell carcinoma, gastrointestinal and pulmonary adenocarcinoma, and metastatic gastrinoma, who died after receiving IL-2-based immunotherapy. Death occurred at intervals ranging from less than 1 hour to 143 days following the last dose of therapy. All patients dying at or less than 43 days following cessation of therapy had lymphoid infiltrates of varying intensity in residual tumor. At necropsy, the major cause of death unrelated to the presence of metastatic tumor was bacterial sepsis. In addition, we found evidence of significant cardiac and pulmonary toxicity: two patients with acute myocardial infarction, one with and one without significant coronary artery disease, two cases of unexplained lymphocytic myocarditis, and one case of fatal pulmonary capillary plugging following an infusion of lymphokine-activated killer cells. Thus, not unlike other forms of therapy for cancer, IL-2-based immunotherapy does not appear to be without significant toxicity.
单独使用白细胞介素-2（IL-2）或与淋巴因子激活的杀伤细胞、肿瘤浸润淋巴细胞或其他免疫治疗药物联合使用，为传统抗肿瘤方案增添了一系列新的选择。关于接受这些药物治疗的患者所发生的病理变化，目前所知甚少。在本研究中，我们回顾了19例患者的尸检材料，其中男性12例，女性7例，患有多种恶性肿瘤，包括黑色素瘤、肾细胞癌、胃肠道和肺腺癌以及转移性胃泌素瘤，这些患者在接受基于IL-2的免疫治疗后死亡。死亡发生在最后一剂治疗后的间隔时间从不到1小时至143天不等。所有在治疗停止后43天或更短时间内死亡的患者，其残留肿瘤中都有不同程度的淋巴细胞浸润。尸检时，与转移性肿瘤存在无关的主要死亡原因是细菌性败血症。此外，我们发现了明显的心脏和肺部毒性证据：两名患者发生急性心肌梗死，一名有明显冠状动脉疾病，一名没有，两例原因不明的淋巴细胞性心肌炎，以及一例在输注淋巴因子激活的杀伤细胞后发生致命的肺毛细血管堵塞。因此，与其他癌症治疗形式一样，基于IL-2的免疫治疗似乎并非没有明显毒性。
