MacFarlane M P, Yang J C, Guleria A S, White R L, Seipp C A, Einhorn J H, White D E, Rosenberg S A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Cancer. 1995 Feb 15;75(4):1030-7. doi: 10.1002/1097-0142(19950215)75:4<1030::aid-cncr2820750420>3.0.co;2-5.
High dose interleukin-2 (IL-2) has been found to produce durable antitumor responses in some patients, benefiting most greatly those patients with melanoma and renal cell carcinoma. In this paper, the hematologic toxicity and changes resulting from high dose IL-2 alone administered by intravenous bolus are discussed.
One hundred ninety-nine consecutive patients treated with high dose IL-2 alone from January 1, 1988 to December 31, 1992 were included in this study. All patients had a diagnosis of metastatic melanoma or metastatic renal cell carcinoma and were treated at the National Cancer Institute (Bethesda, MD).
Anemia, requiring erythrocyte transfusions, occurred in 14% of all treatment courses, with a median of two units of erythrocytes transfused. Severe leukopenia ( < 1,000 leukocytes/mm3) was rare (1.5% of all patients) and was not associated with any infectious complications. Severe thrombocytopenia ( < 30,000 platelets/mm3) occurred in 2.2% of all treatment cycles, with two patients experiencing a grade 3 hemorrhage, defined as gross blood loss, and one patient experiencing a grade 4 hemorrhage, defined as a debilitating blood loss. Defects in the coagulation pathway were common: abnormal partial thromboplastin time and prothrombin time values occurred in 64% and 25% of the treatment cycles, respectively. In addition, a mean clearance of 93% of lymphocytes from the peripheral blood was observed within 24 hours after initiating IL-2 therapy. This was followed by rebound lymphocytosis to a mean of 198% of baseline on posttreatment Day 4. There were no treatment-related deaths.
During IL-2 therapy, adverse sequelae of anemia, thrombocytopenia, coagulopathy, and leukopenia were usually mild, transient and rarely limited therapy. A profound decrease in lymphocytes in the peripheral circulation occurred within 24 hours after initiating therapy, with a rebound occurring after stopping IL-2. No specific hematologic parameter was associated significantly with a patient's increased probability of responding to therapy.
已发现高剂量白细胞介素-2（IL-2）可使部分患者产生持久的抗肿瘤反应，对黑素瘤和肾细胞癌患者益处最大。本文讨论了静脉推注单独使用高剂量IL-2所导致的血液学毒性及变化。
本研究纳入了1988年1月1日至1992年12月31日期间连续接受单独高剂量IL-2治疗的199例患者。所有患者均被诊断为转移性黑素瘤或转移性肾细胞癌，并在美国国立癌症研究所（马里兰州贝塞斯达）接受治疗。
在所有治疗疗程中，14%出现需要输注红细胞的贫血，输注红细胞的中位数为2个单位。严重白细胞减少（白细胞计数<1000/mm³）罕见（占所有患者的1.5%），且与任何感染并发症均无关联。严重血小板减少（血小板计数<30000/mm³）出现在所有治疗周期的2.2%，2例患者发生3级出血（定义为大量失血），1例患者发生4级出血（定义为导致身体衰弱的失血）。凝血途径缺陷很常见：活化部分凝血活酶时间和凝血酶原时间异常分别出现在64%和25%的治疗周期中。此外，在开始IL-2治疗后24小时内，观察到外周血淋巴细胞平均清除率达93%。随后在治疗后第4天出现淋巴细胞增多反弹，平均升至基线的198%。无治疗相关死亡病例。
在IL-2治疗期间，贫血、血小板减少、凝血病和白细胞减少的不良后果通常较轻、短暂，很少限制治疗。治疗开始后24小时内，外周循环中的淋巴细胞显著减少，停止IL-2治疗后出现反弹。没有特定的血液学参数与患者对治疗反应增加的可能性显著相关。
