Valteau-Couanet D, Rubie H, Meresse V, Farace F, Brandely M, Hartmann O
Pediatrics Department, Institut Gustave Roussy, Villejuif, France.
Bone Marrow Transplant. 1995 Oct;16(4):515-20.
Despite intensification of treatment with high-dose chemotherapy (HDC) and autologous bone marrow transplantation (AMBT), the prognosis of poorly responding metastatic neuroblastoma remains bad. Recombinant IL-2 (rIL-2) was used after ABMT to enhance the immune response against the tumor and thereby to improve survival of these patients. In this study, five courses of rIL-2 were administered as a continuous intravenous infusion every 2 weeks, the first course lasting 5 days, and the other four 2 days. rIL-2 treatment was to begin within 120 days of BMT. This study demonstrates the feasibility of rIL-2 soon after HDC and ABMT. The maximum tolerated dose (MTD) was 12 x 10(6) U/m2/day. Clinical toxicity was similar to that observed in adults, moderately increased by the proximity of ABMT; in a previous study we demonstrated that the MTD in non-grafted children was 18 x 10(6) U/M2/day. Nevertheless, half of the patients were not able to receive rIL-2 therapy after ABMT, and only 6/12 received 100% of the planned dose, mainly because of thrombocytopenia. If peripheral stem cell transplantation is demonstrated to enhance platelet recovery, more patients could be treated with rIL-2 with the present schedule. Earlier administration of low-dose rIL-2 after BMT associated with ex vivo rIL-2 treatment of the graft could be a more valid way of using rIL-2 to improve survival.
尽管采用大剂量化疗（HDC）和自体骨髓移植（AMBT）强化治疗，但转移性神经母细胞瘤反应欠佳者的预后仍然很差。自体骨髓移植后使用重组白细胞介素-2（rIL-2）来增强针对肿瘤的免疫反应，从而提高这些患者的生存率。在本研究中，每2周连续静脉输注rIL-2共五个疗程，第一个疗程持续5天，其余四个疗程持续2天。rIL-2治疗在骨髓移植后120天内开始。本研究证明了大剂量化疗和自体骨髓移植后不久使用rIL-2的可行性。最大耐受剂量（MTD）为12×10⁶U/m²/天。临床毒性与在成人中观察到的相似，因自体骨髓移植的临近而适度增加；在先前的一项研究中，我们证明未进行移植的儿童的最大耐受剂量为18×10⁶U/m²/天。然而，一半的患者在自体骨髓移植后无法接受rIL-2治疗，只有6/12的患者接受了计划剂量的100%，主要原因是血小板减少症。如果证明外周干细胞移植可促进血小板恢复，那么按照目前的方案，更多患者可以接受rIL-2治疗。骨髓移植后早期给予低剂量rIL-2并结合移植物的体外rIL-2处理可能是使用rIL-2提高生存率的更有效方法。
