Quan Walter D Y, Khan Nawazish, Ramirez Maria, Taylor W Chris, Quan Francine, Vinogradov Mikhail, Walker Paul
Medical Oncology and Hematology, Medical College of Ohio, Toledo, OH 43614, USA.
Cancer Biother Radiopharm. 2005 Apr;20(2):151-4. doi: 10.1089/cbr.2005.20.151.
The administration of high-dose continuous intravenous infusion interleukin-2 (IL-2) is able to induce the presence of lymphokine-activated killer (LAK) cells. LAK are able to nonspecifically lyse tumor cells. They are also able to lyse endothelial cells, which accounts for, at least in part, the capillary leak syndrome seen as one of the toxicities with this therapy. A pulmonary manifestation of capillary leak syndrome is the presence of pulmonary edema. We postulated that capillary leak may also be a mechanism by which LAK could conceivably reach pulmonary metastases or could be a reflection of damage of endothelial cells in vasculature supplying metastases and that capillary leak syndrome may actually correlate with the response of pulmonary metastases. We examined our database of patients with lung metastases treated with high-dose continuous infusion IL-2 (18 MIU/m(2)/day for 3 days) regimens. Eighteen patients had the following characteristics: melanoma (11), renal cancer (7), median age of 67 years (range, 28-79 years), and males (15). All patients were treated by oncology nurses on either the stem cell transplant unit or oncology ward. Pulmonary edema was defined as the presence of pleural fluid on a chest X-ray, computed tomography (CT) scan, and/or as noted on a physical examination by at least 2 observers. No patients required endotracheal intubation, mechanical ventilation, or an intensive care unit transfer. The median number of cycles received was 6 (range, 1-13). All 8 responding patients (6 patients with melanoma, 2 patients with kidney cancer) manifested pulmonary edema during interleukin-2 therapy. Four patients with pulmonary edema were nonresponders. The presence of pulmonary edema correlated with the response to therapy (p = 0.01). The median duration of response of pulmonary nodules was 5 months (range, 1-16 months). There is a correlation between the development of pulmonary edema and the response of pulmonary metastases in patients with melanoma and kidney cancer treated with high-dose continuous infusion interleukin-2.
大剂量持续静脉输注白细胞介素-2（IL-2）能够诱导淋巴因子激活的杀伤细胞（LAK细胞）的出现。LAK细胞能够非特异性地裂解肿瘤细胞。它们也能够裂解内皮细胞，这至少部分解释了毛细血管渗漏综合征，该综合征是这种治疗的毒性反应之一。毛细血管渗漏综合征的肺部表现为肺水肿。我们推测，毛细血管渗漏可能也是LAK细胞到达肺转移灶的一种机制，或者可能是供应转移灶的脉管系统中内皮细胞受损的一种反映，并且毛细血管渗漏综合征可能实际上与肺转移灶的反应相关。我们检查了接受大剂量持续输注IL-2（18 MIU/m²/天，共3天）方案治疗的肺转移患者数据库。18例患者具有以下特征：黑色素瘤（11例）、肾癌（7例），中位年龄67岁（范围28 - 79岁），男性（15例）。所有患者均由干细胞移植科或肿瘤科护士在相应科室进行治疗。肺水肿定义为胸部X线、计算机断层扫描（CT）或至少2名观察者体格检查发现胸腔积液。没有患者需要气管插管、机械通气或转入重症监护病房。接受治疗的中位周期数为6个（范围1 - 至13个）。所有8例有反应的患者（6例黑色素瘤患者，2例肾癌患者）在白细胞介素-2治疗期间均出现肺水肿。4例出现肺水肿的患者无反应。肺水肿的出现与治疗反应相关（p = 0.01）。肺结节的中位反应持续时间为5个月（范围1 - 16个月）。在接受大剂量持续输注白细胞介素-2治疗的黑色素瘤和肾癌患者中，肺水肿的发生与肺转移灶的反应之间存在相关性。
