Sievers E L, Lange B J, Sondel P M, Krailo M D, Gan J, Tjoa T, Liu-Mares W, Feig S A
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Cancer J Sci Am. 2000 Feb;6 Suppl 1:S39-44.
Up to 80% of children with acute myelogenous leukemia treated with intensive chemotherapy achieve remission; however, a large proportion of patients develops recurrent disease. Because interleukin (IL)-2 can induce remission in patients with overt evidence of acute myelogenous leukemia, we hypothesized that it might prevent relapse when administered to patients in first remission after intensive consolidation chemotherapy. A pilot Children's Cancer Group (CCG) trial (CCG-0941) demonstrated the feasibility of this approach, and we initiated a prospective randomized trial (CCG-2961) to further evaluate the safety and potential efficacy of IL-2 therapy in preventing relapse of acute myelogenous leukemia.
In trial CCG-0941, 21 pediatric patients in complete remission following induction and consolidation chemotherapy on protocol CCG-2941 received IL-2 therapy. In CCG-2961, 79 patients in complete remission were randomized as of February 1999 to receive either IL-2 (n = 39) or no further therapy. In both trials, recombinant IL-2 was given at a dose of 9 million IU/m2/d by continuous intravenous infusion for 4 days. After 4 days of rest, IL-2 was resumed at a dose of 1.6 million IU/m2/d for 10 days by continuous infusion. We monitored patients for toxicity and relapse.
The majority of patients treated with IL-2 in these two trials experienced some degree of fever. Seven of 60 patients (12%) had clinically significant rashes, and grade 3 vascular leak syndrome and hypotension have each been observed in five patients (8%). Hypotension resolved promptly after treatment with intravenous fluids. No patients have experienced renal toxicity or required cardiac vasopressors or transfer to an intensive care unit; there have been no treatment-related deaths. Overall, the incidence and severity of adverse events remain similar in the two trials. Total projected accrual to the IL-2 randomization is anticipated to be 326 patients, and relapse and survival data remain blinded.
The dose and schedule of IL-2 used in these two trials continue to be reasonably well tolerated by children with acute myelogenous leukemia in first remission. Any conclusions with regard to efficacy must await completion of the randomized trial.
接受强化化疗的急性髓性白血病患儿中，高达80%可实现缓解；然而，很大一部分患者会出现疾病复发。由于白细胞介素（IL）-2可使有明显急性髓性白血病证据的患者缓解，我们推测在强化巩固化疗后处于首次缓解期的患者中给予IL-2可能会预防复发。儿童癌症组（CCG）的一项试点试验（CCG-0941）证明了这种方法的可行性，我们启动了一项前瞻性随机试验（CCG-2961），以进一步评估IL-2疗法预防急性髓性白血病复发的安全性和潜在疗效。
在CCG-0941试验中，21例按照CCG-2941方案诱导和巩固化疗后完全缓解的儿科患者接受了IL-2治疗。在CCG-2961试验中，截至1999年2月，79例完全缓解的患者被随机分为两组，一组接受IL-2治疗（n = 39），另一组不再接受进一步治疗。在两项试验中，重组IL-2均以900万IU/m²/天的剂量持续静脉输注4天。休息4天后，以160万IU/m²/天的剂量通过持续输注恢复IL-2治疗10天。我们对患者的毒性和复发情况进行监测。
在这两项试验中，接受IL-2治疗的大多数患者都出现了一定程度的发热。60例患者中有7例（12%）出现了具有临床意义的皮疹，5例患者（8%）分别出现了3级血管渗漏综合征和低血压。低血压经静脉补液治疗后迅速缓解。没有患者出现肾毒性，也无需使用心脏血管加压药或转入重症监护病房；没有与治疗相关的死亡病例。总体而言，两项试验中不良事件的发生率和严重程度相似。预计IL-2随机分组的总入组人数为326例患者，复发和生存数据仍处于盲态。
这两项试验中使用的IL-2剂量和给药方案对于首次缓解期的急性髓性白血病患儿仍具有较好的耐受性。关于疗效的任何结论都必须等待随机试验完成。
