Researchers affiliated with the Children’s Oncology Group have reported that high-dose chemoradiotherapy and autologous stem cell rescue is more effective than conventional-dose chemotherapy for children with high-risk neuroblastoma. The details of this study appeared in the March 1, 2009 issue of the Journal of Clinical Oncology.[1]

High-dose therapy is frequently used to treat patients with recurrent neuroblastoma, but the role of high-dose therapy in up-front treatment of poor-risk patients is less well defined. A randomized trial published in 1999 found that event-free survival (EFS) was 34% in patients with high-risk neuroblastoma receiving high-dose therapy compared with 22% for those receiving three cycles of intensive chemotherapy.[2] Retinoic acid maintenance was beneficial in both arms of the study.

Researchers from Europe have reported that children with poor-risk neuroblastoma who receive high-dose chemotherapy and autologous stem cell support have a superior survival compared with patients receiving maintenance chemotherapy.[3] In another study, researchers in England performed a randomized trial evaluating high-dose Alkeran® (melphalan) in children with advanced neuroblastoma who responded to induction therapy.[4] They reported that the five-year EFS was 38% in the high-dose group and 27% in the control group. For patients with Stage IV disease, the differences were more marked with a five-year EFS of 33% for the high-dose group and 17% for the control group.

The current study involved 379 patients with high-risk neuroblastoma who were randomly allocated to receive consolidation therapy with myeloablative chemoradiotherapy and autologous purged marrow transplant or consolidation with conventional doses of chemotherapy. Patients in both groups were randomized to receive or not receive retinoic acid after completion of consolidation.

The following table summarizes the main findings of this trial based on original assignment:

Table 1: Conventional Chemotherapy Versus Autologous Transplant in Neuroblastoma

Retinoic acid maintenance significantly improved the overall survival of patients receiving conventional chemotherapy or autologous transplantation. For example, patients assigned to receive an autologous transplant and retinoic acid had a 59% five-year survival from the time of second randomization compared with 41% for patients not receiving retinoic acid.

These authors concluded: “Myeloablative therapy and autologous hematopoietic cell rescue result in significantly better 5-year EFS and OS than nonmyeloablative chemotherapy; cis=RA given after consolidation independently results in significantly improved OS.”

Comments: These data are consistent with other randomized trials showing the superiority of high-dose over conventional-dose consolidation therapy for patients with poor risk neuroblastoma.

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