Diaz M A, Vicent M G, Madero L
Department of Pediatric Hematology and Oncology, Niño Jesús Children's Hospital, Autonomous University of Madrid, Spain.
Bone Marrow Transplant. 1999 Dec;24(11):1157-9. doi: 10.1038/sj.bmt.1702042.
We conducted a prospective pilot study to assess the feasibility and safety of high-dose busulfan/melphalan as conditioning therapy prior to autologous PBPC transplantation in pediatric patients with high-risk solid tumors. From January 1995 to January 1999, 30 patients aged 2-21 years (median 8) were entered into the study. There were 14 females and 16 males. Diagnoses included neuroblastoma in 10 patients; Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) in 15 patients and rhabdomyosarcoma in five patients. Treatment consisted of busulfan 16 mg/kg, orally over 4 days (from days -5 to -2) in 6 hourly divided doses, and melphalan at a dose of 140 mg/m2 given by intravenous infusion over 5 min on day -1. G-CSF mobilized PBPC were used as autologous stem-cell rescue. One patient developed a single generalized convulsion during busulfan therapy. The most relevant non-hematologic toxicity was gastrointestinal, manifesting as grade 2-3 mucositis and diarrhea in 12 patients. Two patients died of procedure-related complications, one from veno-occlusive disease of liver and multiorgan failure and the other from adult respiratory distress syndrome. Probability of treatment-related mortality was 6.6 +/- 4.5%. With a median follow-up of 18 months (range, 1-48), 19 patients are alive and disease-free, the actuarial EFS at 4 years being 55 +/- 12% for the whole group. We conclude that high-dose busulfan/melphalan for autologous transplantation in children with solid tumors is feasible even in small patients. It is well-tolerated, with an acceptable transplant-related mortality and has proven antitumor activity.
我们开展了一项前瞻性试验研究，以评估高剂量白消安/美法仑作为预处理疗法在高危实体瘤儿科患者自体外周血祖细胞移植前的可行性和安全性。1995年1月至1999年1月，30名年龄在2至21岁（中位年龄8岁）的患者进入该研究。其中女性14名，男性16名。诊断包括10例神经母细胞瘤；15例尤因肉瘤和外周神经外胚层肿瘤（PNET）以及5例横纹肌肉瘤。治疗方案为白消安16mg/kg，于-5至-2天口服共4天，每6小时分剂量服用，美法仑剂量为140mg/m²，于-1天静脉输注5分钟。粒细胞集落刺激因子动员的外周血祖细胞用作自体干细胞救援。1例患者在白消安治疗期间出现单次全身性惊厥。最相关的非血液学毒性为胃肠道毒性，12例患者表现为2 - 3级粘膜炎和腹泻。2例患者死于与治疗相关的并发症，1例死于肝静脉闭塞病和多器官功能衰竭，另1例死于成人呼吸窘迫综合征。治疗相关死亡率为6.6±4.5%。中位随访18个月（范围1 - 48个月），19例患者存活且无疾病，全组4年无事件生存率精算值为55±12%。我们得出结论，高剂量白消安/美法仑用于实体瘤儿童的自体移植即使在小患者中也是可行的。其耐受性良好，移植相关死亡率可接受，且已证明具有抗肿瘤活性。
