title: High-dose busulfan/melphalan as conditioning for autologous PBPC transplantation in pediatric patients with solid tumors.
abstract: 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.
authors.affiliation: Department of Pediatric Hematology and Oncology, Niño Jesús Children's Hospital, Autonomous University of Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Diaz
authors.forename: M G
authors.initials: MG
authors.lastname: Vicent
authors.forename: L
authors.initials: L
authors.lastname: Madero
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001772:Blood Cell Count; D001847:Bone Diseases / Q000139:chemically induced; D001859:Bone Neoplasms / Q000188:drug therapy; D002066:Busulfan / Q000008:administration & dosage* / Q000633:toxicity*; D002648:Child; D002675:Child, Preschool; D002998:Clonazepam / Q000008:administration & dosage* / Q000633:toxicity*; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy*; D009447:Neuroblastoma / Q000188:drug therapy; D010865:Pilot Projects; D012189:Retrospective Studies; D012208:Rhabdomyosarcoma / Q000188:drug therapy; D012512:Sarcoma, Ewing / Q000188:drug therapy; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D002998:Clonazepam; D002066:Busulfan; D008558:Melphalan