Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: Results of AML-BFM 98
Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: Results of AML-BFM 98
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DOI：
10.1200/jco.2006.06.5037
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发表时间：
2006-09-20
影响因子：
45.3
通讯作者：
Reinhardt, Dirk
中科院分区：
文献类型：
--
作者：
Creutzig, Ursula;Zimmermann, Martin;Reinhardt, Dirk
目的通过随机比较两个短期巩固治疗周期与柏林-法兰克福-明斯特（BFM）型双相6周巩固治疗和预防性应用粒细胞集落刺激因子（G-CSF）与不应用G-CSF的疗效，以改善儿童急性髓系白血病（AML）的预后。此外，标准风险患者的治疗加强了第二次诱导，HAM（高剂量阿糖胞苷和米托蒽醌）。患者和MethodsFourhund-Seventy-Three患者年龄小于18岁，新发AML参加了试验AML-BFM 98。患者接受了5个疗程的强化化疗，颅脑照射，和1年的维持therapy. ResultsFour-hundred例（88%）达到缓解。与试验AML-BFM 93相比，早期死亡率从7.4%降至3.2%（P =.005），5年总生存率从58%增至62%（对数秩P =.03）。两种类型的巩固治疗导致相似的结局（无事件生存率，51%对50%），但在两个周期组中，治疗持续时间较短（中位持续时间，15天），治疗相关死亡率较低（5对9例患者）。G-CSF缩短了中性粒细胞减少，但没有降低严重感染的发生率。强化诱导治疗并没有改善预后的标准风险患者（无事件生存，62%对67%）。ConclusionOverall results都没有改善的管理G-CSF，也不是周期治疗，但是，后者更容易执行。与AML-BFM 93研究相比，标准风险患者中HAM强化治疗并未改善预后。未来的治疗设计必须平衡强化治疗与更高的毒性，改善支持性护理，并考虑替代治疗策略。
PurposeTo improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone).Patients and MethodsFour hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy.ResultsFour hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P =.005), and 5-year overall survival increased from 58% to 62% (log-rank P =.03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%).ConclusionOverall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.