Treatment of high-risk relapsed Wilms tumor with dose-intensive chemotherapy, marrow-ablative chemotherapy, and autologous hematopoietic stem cell support: Experience by the Italian association of pediatric hematology and oncology

Abstract Background. We evaluated an intensified chemotherapy strategy in children with Wilms tumor who relapsed with high-risk features. Procedures. From January 2001 to June 2006, we treated 20 consecutive children with reinduction chemotherapy (using ifosfamide/carboplatin/etoposide in 15/20 cases), with m = 15) or without (n=5) subsequent high-dose chemotherapy and hematopoietic stern cell support, surgery where feasible, and radiation therapy. The median time to relapse was 10 months after nephrectomy. All but two children initially received doxorubicin as first-line therapy. Results. All patients were assessed for outcome: 13 are currently alive, 12 of them in remission a median 25 months since their relapse, one with progressing tumor. The treatment was unsuccessful in eight children: the disease progressed during reinduction in three, and relapsed in five. There was one toxic death. All transplanted patients engrafted to a neutrophil count >0.5 X 10(3)/mu l after a rnedian 11 days, and to an unsustained platelet count >25,000/mu l after a median of 13 days. Three-year disease-free and overall survival rates were 56 +/- 12% and 55 +/- 13%, respectively. Neither recurrence within 12 months of nephrectomy nor extra-lung recurrence negatively affected outcome. A survival advantage was demonstrated in patients without disease evidence prior to transplant. Conclusion. A disease-free survival rate nearing 50% is a realistic target in children with high-risk recurrent Wilms tumor. The benefit of autologous hematopoietic stein cell transplantation for consolidation deserves to be investigated in a randomized, controlled study