Pediatric Oncology/Hematology, VU University Medical Center, De Boelelaan 1117, NL-1081HV Amsterdam, the Netherlands.
J Clin Oncol. 2013 Feb 10;31(5):599-607. doi: 10.1200/JCO.2012.43.7384. Epub 2013 Jan 14.
In pediatric relapsed acute myeloid leukemia (AML), optimal reinduction therapy is unknown. Studies suggest that liposomal daunorubicin (DNX; DaunoXome; Galen, Craigavon, United Kingdom) is effective and less cardiotoxic, which is important in this setting. These considerations led to a randomized phase III study by the International Berlin-Frankfurt-Münster Study Group.
Patients with relapsed or primary refractory non-French-American-British type M3 AML who were younger than 21 years of age were eligible. Patients were randomly assigned to fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) or to FLAG plus DNX in the first reinduction course. The primary end point was status of the bone marrow (BM) sampled shortly before the second course of chemotherapy (the day 28 BM). Data are presented according to intention-to-treat for all 394 randomly assigned patients (median follow-up, 4.0 years).
The complete remission (CR) rate was 64%, and the 4-year probability of survival (pOS) was 38% (SE, 3%). The day 28 BM status (available in 359 patients) was good (≤ 20% leukemic blasts) in 80% of patients randomly assigned to FLAG/DNX and 70% for patients randomly assigned to FLAG (P = .04). Concerning secondary end points, the CR rate was 69% with FLAG/DNX and 59% with FLAG (P = .07), but overall survival was similar. However, core-binding factor (CBF) AML treated with FLAG/DNX resulted in pOS of 82% versus 58% with FLAG (P = .04). Grade 3 to 4 toxicity was essentially similar in both groups.
DNX added to FLAG improves early treatment response in pediatric relapsed AML. Overall long-term survival was similar, but CBF-AML showed an improved survival with FLAG/DNX. International collaboration proved feasible and resulted in the best outcome for pediatric relapsed AML reported thus far.
在儿科复发性急性髓细胞白血病（AML）中，最佳的再诱导治疗方法尚不清楚。有研究表明，脂质体柔红霉素（DNX；DaunoXome；Galen，Craigavon，英国）具有疗效且心脏毒性较小，这在这种情况下非常重要。这些考虑因素促使国际柏林-法兰克福-明斯特研究小组进行了一项随机 III 期研究。
年龄小于 21 岁且患有复发或原发性难治性非法美英（French-American-British）M3 AML 的患者符合入组条件。患者被随机分配到氟达拉滨、阿糖胞苷和粒细胞集落刺激因子（FLAG）组或 FLAG 加 DNX 组，用于第一个再诱导疗程。主要终点是第二个化疗疗程前（第 28 天骨髓）采样的骨髓（BM）状态。根据所有 394 例随机分配患者的意向治疗原则（中位随访时间 4.0 年），报告数据。
完全缓解（CR）率为 64%，4 年生存率（pOS）为 38%（标准误差，3%）。第 28 天 BM 状态（359 例患者中有可评估数据）在随机分配到 FLAG/DNX 组的患者中为 80%（≤ 20%白血病细胞），而在随机分配到 FLAG 组的患者中为 70%（P =.04）。关于次要终点，FLAG/DNX 组的 CR 率为 69%，FLAG 组为 59%（P =.07），但总生存情况相似。然而，用 FLAG/DNX 治疗的核心结合因子（CBF）AML 患者的 pOS 为 82%，而用 FLAG 治疗的患者为 58%（P =.04）。两组的 3 级至 4 级毒性基本相似。
DNX 联合 FLAG 可改善儿科复发性 AML 的早期治疗反应。总体长期生存情况相似，但 CBF-AML 用 FLAG/DNX 治疗的生存情况得到改善。国际合作证明是可行的，为儿科复发性 AML 迄今为止取得了最佳的结果。
