Welte K, Reiter A, Mempel K, Pfetsch M, Schwab G, Schrappe M, Riehm H
Department of Pediatric Hematology and Oncology, Medical School Hannover, Germany.
Blood. 1996 Apr 15;87(8):3143-50.
Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia (ALL) are good, with event-free survival (EFS) rates over 70%. However, for a subset of patients characterized by high-risk (HR) features the outcome is less favorable, with EFS rates below 50%. Intensification of chemotherapy may improve the outcome for those patients, but increased toxicity, particularly myelosuppression, limits the escalation of dose intensity. Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) is known to reduce myelosuppression after cancer chemotherapy in adults. The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy. Patients with HR pediatric ALL were randomized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Münster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously. In both groups, the planned interval between chemotherapy courses was a minimum of 21 days. We report here interim results of 34 patients. The incidence of febrile neutropenia (absolute neutrophil count <0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C) was 17% in children receiving r-metHuG-CSF, as compared with 40% in the control group (P = .007). In addition, the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient (P = .02). Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group (8% v 15%; P = .04), and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient (P = .02). A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF (P = .007). With a median follow-up of 3.3 years, the estimated EFS of 4 years is 41% +/- 12%. In conclusion, r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia, culture-confirmed infections, and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule.
小儿急性淋巴细胞白血病（ALL）的整体化疗效果良好，无事件生存率（EFS）超过70%。然而，对于一部分具有高危（HR）特征的患者，预后较差，EFS低于50%。强化化疗可能改善这些患者的预后，但毒性增加，尤其是骨髓抑制，限制了剂量强度的提升。已知重组甲硫氨酰人粒细胞集落刺激因子（r-metHuG-CSF）可减轻成人癌症化疗后的骨髓抑制。本研究的目的是检验r-metHuG-CSF对HR小儿ALL患者骨髓抑制及化疗总体缓解率的影响。HR小儿ALL患者根据德国ALL-柏林-法兰克福-明斯特90方案被随机分为两组，一组单独接受9个交替周期的化疗，另一组在化疗后预防性皮下注射剂量为5μg/kg/d的r-metHuG-CSF。两组中，化疗疗程之间的计划间隔至少为21天。我们在此报告34例患者的中期结果。接受r-metHuG-CSF治疗的儿童中，发热性中性粒细胞减少症（绝对中性粒细胞计数<0.5×10⁹/L且口腔温度≥38.5℃）的发生率为17%，而对照组为40%（P = 0.007）。此外，每位患者发热性中性粒细胞减少症的中位总持续时间从20.3天降至6.2天（P = 0.02）。r-metHuG-CSF组中培养确诊感染的发生频率较低（8%对15%；P = 0.04），每位患者静脉使用抗生素的总持续时间从32.2天显著降至18.2天（P = 0.02）。r-metHuG-CSF也有助于更严格地遵守计划治疗方案（P = 0.007）。中位随访3.3年，4年的估计EFS为41%±12%。总之，在化疗疗程间隔期预防性使用r-metHuG-CSF可显著降低发热性中性粒细胞减少症、培养确诊感染及静脉使用抗生素的持续时间，并有助于更严格地遵守治疗方案。
