Autologous stem cell transplantation for high-risk pediatric solid tumors

Many solid tumors exhibit a steep dose-response to alkylating agents, and autologous stem cell transplantation (ASCT) allows escalation of the chemotherapy dose for treatment of high risk solid tumors. We have transplanted 24 children and young adults with relapsed or metastatic solid tumors on two consecutive ASCT protocols consisting primarily (protocol MT 8911) or exclusively (MT 9408) of alkylating agents. The median time to neutrophil engraftment was 21 days in protocol MT 8911 (no prophylactic use of growth factors) and 14 days in MT 9408 (G-CSF, 5 μg/kg, started on day 0). Disease-free survival estimated by the Kaplan-Meier method is 39% (95% CI: 19-59%) at 2 years after transplant and 34% (95% CI: 14-54%) at 4 years after transplant. Six of the nine patients with metastatic or relapsed disease that were transplanted while in complete remission (four patients with Ewing's sarcoma family of tumors and two patients with anaplastic Wilms tumor) are alive and disease-free with a median follow-up of 37 months (range 20-74 months). The estimated 4 year survival for patients receiving a transplant while in high risk remission was 78% (95% CI: 51-100%). In contrast, 13/15 patients that were transplanted while in partial remission died because of progressive disease or transplant-related complications. There were three transplant-related deaths (12.5%), including one patient with multiorgan failure, and two patients with complications of hepatic veno-occlusive disease. Our data indicate that autologous stem cell transplantation should be considered for consolidation therapy of high risk and relapsed pediatric patients with solid tumors who have achieved complete remission.