López-Jiménez J, Pérez-Oteyza J, Munoz A, Parra C, Villalón L, Ramos P, Maldonado M, García-Laraña J, Otheo E, Roldán E, García-Avello A, Odriozola J
Department of Haematology, Universidad de Alcala de Henares, Madrid, Spain.
Bone Marrow Transplant. 1997 Mar;19(5):429-34. doi: 10.1038/sj.bmt.1700693.
Use of IL-2 therapy after autologous transplantation is currently being explored to reduce relapse rate. Low doses of the cytokine induce significant immunomodulation avoiding the severe side-effects associated with high-dose IL-2 therapy. However, low-dose IL-2 is usually given by continuous infusion through central venous lines with the consequent risks of thrombosis and infections. Twenty-six consecutive patients who received autologous transplants received low-dose IL-2 after stable engraftment had been achieved. The first 13 patients (group A) were scheduled to receive 400,000/IU/m2/day for 3 months by continuous intravenous infusion. Ten of these patients suffered infectious episodes, mainly bacteriemias that often necessitated delaying IL-2 therapy (median delivered dose: 32% of planned). The next 13 patients were then assigned to receive IL-2 (800,000-1,000,000 IU/m2/day for 3 months) subcutaneously (group B). For group B patients, median dose intensity was 84% (P = 0.01 when compared with group A patients). Only one severe infectious episode was observed in these patients. Clinical toxicity in group B patients consisted mainly of s.c. nodules. Immunomodulation, measured as an increase in the absolute number of CD56+ cells and CD56+(bright) cells, was higher in patients who received the cytokine by the subcutaneous route (median peak increase of CD56+ cells: 160 and 220% for group A and B patients respectively; median peak increase of CD56+(bright) cells: 210% and 310% for group A and B respectively, P < 0.05 between groups A and B). No statistically significant increment of T lymphocytes was observed in any group. No hematologic toxicity was observed apart from eosinophilia, which was very marked in group B (P < 0.01). Our results show that low-dose s.c. IL-2 therapy is associated with low clinical and hematologic toxicity after autologous transplantation. The immunomodulation achieved is no less than that achieved with the i.v. approach.
目前正在探索自体移植后使用白细胞介素-2（IL-2）疗法以降低复发率。低剂量的细胞因子可诱导显著的免疫调节作用，同时避免了与高剂量IL-2疗法相关的严重副作用。然而，低剂量IL-2通常通过中心静脉导管持续输注给药，从而带来血栓形成和感染的风险。26例接受自体移植的连续患者在实现稳定植入后接受了低剂量IL-2治疗。前13例患者（A组）计划通过持续静脉输注接受400,000国际单位/平方米/天的治疗，持续3个月。这些患者中有10例发生感染性事件，主要是菌血症，这常常需要推迟IL-2治疗（中位给药剂量：计划剂量的32%）。接下来的13例患者随后被分配接受皮下注射IL-2（800,000-1,000,000国际单位/平方米/天，持续3个月）（B组）。对于B组患者，中位剂量强度为84%（与A组患者相比，P = 0.01）。在这些患者中仅观察到1例严重感染性事件。B组患者的临床毒性主要表现为皮下结节。以CD56+细胞和CD56+(明亮)细胞绝对数量增加来衡量的免疫调节作用，在通过皮下途径接受细胞因子治疗的患者中更高（A组和B组患者CD56+细胞的中位峰值增加分别为160%和220%；A组和B组患者CD56+(明亮)细胞的中位峰值增加分别为210%和310%，A组和B组之间P < 0.05）。在任何一组中均未观察到T淋巴细胞有统计学意义的增加。除了嗜酸性粒细胞增多症外未观察到血液学毒性，嗜酸性粒细胞增多症在B组中非常明显（P < 0.01）。我们的结果表明，自体移植后低剂量皮下注射IL-2疗法与低临床和血液学毒性相关。所实现的免疫调节作用不亚于静脉注射途径所实现的免疫调节作用。
