Villani F, Galimberti M, Rizzi M, Manzi R
Divisione di Fisiopatologia Cardiorespiratoria, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Eur Respir J. 1993 Jun;6(6):828-33.
The aim of the present investigation was to evaluate lung toxicity in 15 patients affected by metastatic melanoma of different sites, and treated with recombinant interleukin-2 (rIL-2) plus lymphokine-activated killer (LAK) cells The treatment regimen included a first and a second course of rIL-2, separated by four consecutive daily leukaphereses. Autologous LAK cells were reinfused during the second course. Lung function was monitored before and after each rIL-2 administration. In the 12 patients who could be followed until completion of the therapy, spirometric parameters and transfer factor of the lungs for carbon monoxide (TLCO) decreased significantly during the first rIL-2 course, remained stable during leukapheresis, and declined significantly further during the second rIL-2 course. In the second phase, chest radiography documented some degree of pulmonary oedema, ranging from interstitial oedema to frank pulmonary oedema. A significant dose-dependent correlation was found between the cumulative rIL-2 dose and the decline in TLCO in the first course of therapy. Moreover, patients who developed symptomatic respiratory insufficiency (World Health Organisation grade III or IV) during the second course of therapy received a higher number of LAK cells than those who did not. The data support the hypothesis that LAK cells have an additional toxic effect on the lung.
本研究的目的是评估15例不同部位转移性黑色素瘤患者接受重组白细胞介素-2（rIL-2）加淋巴因子激活的杀伤细胞（LAK）治疗后的肺毒性。治疗方案包括两个疗程的rIL-2，中间间隔连续4天的白细胞分离术。在第二个疗程中回输自体LAK细胞。在每次给予rIL-2之前和之后监测肺功能。在12例能够随访至治疗结束的患者中，在第一个rIL-2疗程期间，肺量计参数和肺一氧化碳转运因子（TLCO）显著下降，在白细胞分离术期间保持稳定，在第二个rIL-2疗程期间进一步显著下降。在第二阶段，胸部X线检查显示有一定程度的肺水肿，从间质性肺水肿到明显的肺水肿。在第一个治疗疗程中，发现累积rIL-2剂量与TLCO下降之间存在显著的剂量依赖性相关性。此外，在第二个治疗疗程中出现症状性呼吸功能不全（世界卫生组织III级或IV级）的患者比未出现的患者接受了更多的LAK细胞。这些数据支持LAK细胞对肺有额外毒性作用的假说。
