Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid

Background Children with high-risk neuroblastoma have a poor outcome. In th is study, we assessed whether myeloablative therapy in conjunction with tra nsplantation of autologous bone marrow improved event-free survival as comp ared with chemotherapy alone, and whether subsequent treatment with 13-cis- retinoic acid (isotretinoin) further improves event-free survival. Methods All patients were treated with the same initial regimen of chemothe rapy, and those without disease progression were then randomly assigned to receive continued treatment with myeloablative chemotherapy, total-body irr adiation, and transplantation of autologous bone marrow purged of neuroblas toma cells or to receive three cycles of intensive chemotherapy alone. All patients who completed cytotoxic therapy without disease progression were t hen randomly assigned to receive no further therapy or treatment with 13-ci s-retinoic acid for six months. Results The mean (+/-SE) event-free survival rate three years after the fir st randomization was significantly better among the 189 patients who were a ssigned to undergo transplantation than among the 190 patients assigned to receive continuation chemotherapy (34+/-4 percent vs. 22+/-4 percent, P = 0 .034). The event-free survival rate three years after the second randomizat ion was significantly better among the 130 patients who were assigned to re ceive 13-cis-retinoic acid than among the 128 patients assigned to receive no further therapy (46+/-6 percent vs. 29+/-5 percent, P = 0.027). Conclusions Treatment with myeloablative therapy and autologous bone marrow transplantation improved event-free survival among children with highrisk neuroblastoma. In addition, treatment with 13-cis-retinoic acid was benefic ial for patients without progressive disease when it was administered after chemotherapy or transplantation. (N Engl J Med 1999; 341:1165-73.) (C)1999 , Massachusetts Medical Society.