Petit Arnaud, Ducassou Stéphane, Leblanc Thierry, Pasquet Marlène, Rousseau Alexandra, Ragu Christine, Cachanado Marine, Nelken Brigitte, Bertrand Yves, Michel Gérard, Gandemer Virginie, Cuccuini Wendy, Fenneteau Odile, Lapillonne Hélène, Auvrignon Anne, Baruchel André, Leverger Guy
Department of Pediatric Hematology and Oncology, Assistance Publique-Hôpitaux de Paris, GH HUEP, Armand Trousseau Hospital, Paris, France; Sorbonne Université, UMRS_938, Paris, France.
Department of Pediatric Hematology and Oncology, Children's Hospital, Bordeaux University, Bordeaux, France.
Hemasphere. 2018 Nov 29;2(6):e159. doi: 10.1097/HS9.0000000000000159. eCollection 2018 Dec.
Despite significant progress in the treatment of pediatric acute myeloblastic leukemia (AML), relapse remains the commonest cause of death. Randomized ELAM02 trial questioned if maintenance therapy with interleukin-2 (IL2), for 1 year, improves disease-free survival (DFS). Patients aged 0 to 18 years, with newly diagnosed AML (excluding patients with acute promyelocytic leukemia or down syndrome AML) were enrolled. They received 1 course of induction treatment (cytarabine and mitoxantrone) and 3 courses of consolidation treatment (high-dose cytarabine in courses 1 and 3). According to the cytogenetics risk, patients not undergoing hematopoietic stem cell transplantation, still in complete remission (CR) after the third course of consolidation treatment, were eligible for randomization to 1 year of maintenance therapy with monthly courses of IL2 or no maintenance treatment. There were 438 evaluable patients, 154 of whom were randomized to the IL2/no maintenance groups. Relapse occurred in 28 patients from the IL2+ group and 29 patients in the IL2- group. Survival was similar in the 2 groups, with a 4-year DFS of 62% without IL2 and 66% with IL2 ( = 0.75). In the CBF population, 4-year DFS was 55% without IL2 and 78% with IL2 ( = 0.07). No deaths from toxicity or excess of serious adverse events related to IL2 treatment were recorded. Prolonged IL2 for maintenance therapy after intensive chemotherapy is feasible and safe in pediatric AML patients in their first CR. Such treatment did not improve DFS in this study, but a positive trend was observed in favor of IL2 maintenance therapy among core binding factor acute myeloblastic leukemia.
尽管小儿急性髓细胞白血病（AML）的治疗取得了显著进展，但复发仍是最常见的死亡原因。随机ELAM02试验探讨了使用白细胞介素-2（IL2）进行1年维持治疗是否能改善无病生存期（DFS）。纳入了年龄在0至18岁、新诊断为AML（不包括急性早幼粒细胞白血病或唐氏综合征AML患者）的患者。他们接受了1个疗程的诱导治疗（阿糖胞苷和米托蒽醌）和3个疗程的巩固治疗（第1和第3疗程使用大剂量阿糖胞苷）。根据细胞遗传学风险，未接受造血干细胞移植且在第三个巩固治疗疗程后仍处于完全缓解（CR）的患者，有资格随机分为接受每月一次IL2的1年维持治疗组或不进行维持治疗组。共有438例可评估患者，其中154例被随机分为IL2/无维持治疗组。IL2+组有28例患者复发，IL2-组有29例患者复发。两组的生存率相似，无IL2时4年DFS为62%，使用IL2时为66%（ = 0.75）。在核心结合因子（CBF）人群中，无IL2时4年DFS为55%，使用IL2时为78%（ = 0.07）。未记录到与IL2治疗相关的毒性死亡或严重不良事件过量。在首次CR的小儿AML患者中，强化化疗后延长IL2进行维持治疗是可行且安全的。在本研究中，这种治疗并未改善DFS，但在核心结合因子急性髓细胞白血病患者中观察到了有利于IL2维持治疗的积极趋势。
