Varan A, Büyükpamukçu M, Kutluk T, Akyüz C
Department of Pediatric Oncology, Hacettepe University, Institute of Oncology, Ankara, Turkey.
Pediatrics. 1999 Feb;103(2):E16. doi: 10.1542/peds.103.2.e16.
The efficacy and safety of recombinant human erythropoietin (rHuEPO) treatment in chemotherapy-induced anemia in children were investigated. rHuEPO is used to treat chemotherapy-induced anemia. Several studies recommend 150 to 300 IU/kg rHuEPO for 2 to 8 months. There are only a few controlled trials in children and no precise data about the optimal dose and duration of rHuEPO treatment is available.
Thirty-four patients receiving chemotherapy for treatment of their solid tumors between October 1996 and June 1997 were included in this study. Patients were randomly selected for each group. The male/female ratio was 20/14, and the median age was 5 years (range, 1-16 years). They had normal hemoglobin levels at the time of diagnosis. When hemoglobin levels decreased to levels lower than 10 g/dL, rHuEPO (150 IU/kg/d, 3 times a week, subcutaneously) was given to 17 patients for 2 months. Their renal, liver, and pulmonary functions were normal. None of the patients had hematologic disease. We did not use any other drugs such as iron or granulocyte colony-stimulating factor. There were 17 patients in the control group. Fifteen patients got chemotherapy regimens including cisplatin (CDDP), but 19 were treated with regimens without CDDP. At the end of rHuEPO treatment, all patients were examined in terms of transfusion requirements and rate of change in hemoglobin levels.
One patient in the study group needed a blood transfusion, whereas 8 patients needed a transfusion in the control group. Patients in the study group had less transfusion requirements compared with the control group. The mean hemoglobin levels before and after the study were 8.48 +/- 0.98 g/dL and 8.41 +/- 1.65 g/dL in the control group and 8.50 +/- 0.85 g/dL and 10.21 +/- 2.14 g/dL in the rHuEPO group, respectively. Optimal hemoglobin increments began in 4 weeks and continued during treatment. CDDP-receiving and CDDP-nonreceiving groups did not have any difference in pretreatment serum erythropoietin levels. rHuEPO treatment was more effective in patients treated with non-CDDP regimens. Mean hemoglobin level increased from 8.68 +/- 0.73 g/dL to 10.26 +/- 1.84 g/dL in 9 patients treated with non-CDDP chemotherapy regimens in the erythropoietin group, although it increased from 8.28 +/- 0.97 g/dL to 10.15 +/- 2.5 g/dL in 8 patients treated with CDDP-containing regimens in the erythropoietin group. rHuEPO caused high blood pressure in only 1 patient that resolved spontaneously after cessation of erythropoietin treatment for a week.
rHuEPO treatment (150 IU/kg/d 3 times a week) is effective and safe in children with chemotherapy-induced anemia. It decreases blood transfusion requirements in solid tumor patients. Our results show that the response to rHuEPO in CDDP-induced anemia is less than the response in non-CDDP receiving patients. Higher doses may be necessary in patients using CDDP.
研究重组人促红细胞生成素（rHuEPO）治疗儿童化疗所致贫血的疗效和安全性。rHuEPO用于治疗化疗所致贫血。多项研究推荐使用150至300国际单位/千克的rHuEPO，治疗2至8个月。儿童中仅有少数对照试验，尚无关于rHuEPO治疗的最佳剂量和疗程的确切数据。
本研究纳入了1996年10月至1997年6月间因实体瘤接受化疗的34例患者。每组患者均为随机选取。男女比例为20/14，中位年龄为5岁（范围1至16岁）。诊断时他们的血红蛋白水平正常。当血红蛋白水平降至低于10克/分升时，17例患者接受rHuEPO（150国际单位/千克/天，每周3次，皮下注射）治疗2个月。他们的肾、肝和肺功能正常。所有患者均无血液系统疾病。我们未使用任何其他药物，如铁剂或粒细胞集落刺激因子。对照组有17例患者。15例患者接受了包括顺铂（CDDP）的化疗方案，但19例接受了不含CDDP的方案治疗。在rHuEPO治疗结束时，对所有患者进行了输血需求和血红蛋白水平变化率方面的检查。
研究组有1例患者需要输血，而对照组有8例患者需要输血。与对照组相比，研究组患者的输血需求更少。研究前后对照组的平均血红蛋白水平分别为8.48±0.98克/分升和8.41±1.65克/分升，rHuEPO组分别为8.50±0.85克/分升和10.21±2.14克/分升。最佳血红蛋白增量在4周时开始，并在治疗期间持续。接受CDDP和未接受CDDP的组在治疗前血清促红细胞生成素水平上无差异。rHuEPO治疗在接受非CDDP方案治疗的患者中更有效。促红细胞生成素组中，9例接受非CDDP化疗方案治疗的患者平均血红蛋白水平从8.68±0.73克/分升升至10.26±1.84克/分升，而促红细胞生成素组中8例接受含CDDP方案治疗的患者平均血红蛋白水平从8.28±0.97克/分升升至10.15±2.5克/分升。rHuEPO仅使1例患者出现高血压，在促红细胞生成素治疗停止1周后自行缓解。
rHuEPO治疗（150国际单位/千克/天，每周3次）对儿童化疗所致贫血有效且安全。它可降低实体瘤患者的输血需求。我们的结果表明，CDDP所致贫血对rHuEPO的反应小于未接受CDDP患者的反应。使用CDDP的患者可能需要更高剂量。
