High-dose busulfan/melphalan as conditioning for autologous PBPC transplantation in pediatric patients with solid tumors

We conducted a prospective pilot study to assess the feasibility and safety of high-dose busulfan/melphalan as conditioning therapy prior to autologou s PBPC transplantation in pediatric patients with high-risk solid tumors. F rom January 1995 to January 1999, 30 patients aged 2-21 years (median 8) we re entered into the study. There were 14 females and 16 males. Diagnoses in cluded neuroblastoma in 10 patients; Ewing's sarcoma and peripheral neuroec todermal 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/m(2) g iven by intravenous infusion over 5 min on day -1, G-CSF mobilized PBPC wer e used as autologous stem-cell rescue. One patient developed a single gener alized convulsion during busulfan therapy, The most relevant non-hematologi c toxicity was gastrointestinal, manifesting as grade 2-3 mucositis and dia rrhea in 12 patients. Two patients died of procedure-related complications, one from veno-occlusive disease of liver and multiorgan failure and the ot her from adult respiratory distress syndrome. Probability of treatment-rela ted 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 yea rs being 55 +/- 12% for the whole group. We conclude that high-dose busulfa n/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.