Long-Term Results for Children With High-Risk Neuroblastoma Treated on a Randomized Trial of Myeloablative Therapy Followed by 13-<i>cis</i>-Retinoic Acid: A Children's Oncology Group Study

TLDR

The study evaluated long‑term outcomes of high‑risk neuroblastoma patients randomized to autologous purged bone marrow transplantation versus chemotherapy, followed by 13‑cis‑retinoic acid. Patients received identical induction chemotherapy, then were randomized to either myeloablative consolidation with total‑body irradiation and ABMT or to intensive chemotherapy, and those who completed consolidation without progression were further randomized to receive 6 months of cis‑RA or no additional therapy. ABMT significantly increased 5‑year event‑free survival compared with intensive chemotherapy (30 % vs 19 %, P = 0.04), whereas 13‑cis‑retinoic acid did not significantly improve event‑free or overall survival; overall survival was higher for each random assignment, but neither ABMT nor cis‑RA alone conferred a significant OS benefit.

Abstract

PURPOSE We assessed the long-term outcome of patients enrolled on CCG-3891, a high-risk neuroblastoma study in which patients were randomly assigned to undergo autologous purged bone marrow transplantation (ABMT) or to receive chemotherapy, and subsequent treatment with 13-cis-retinoic acid (cis-RA). PATIENTS AND METHODS Patients received the same induction chemotherapy, with random assignment (N = 379) to consolidation with myeloablative chemotherapy, total-body irradiation, and ABMT versus three cycles of intensive chemotherapy. Patients who completed consolidation without disease progression were randomly assigned to receive no further therapy or cis-RA for 6 months. Results The event-free survival (EFS) for patients randomly assigned to ABMT was significantly higher than those randomly assigned to chemotherapy; the 5-year EFS (mean +/- SE) was 30% +/- 4% versus 19% +/- 3%, respectively (P = .04). The 5-year EFS (42% +/- 5% v 31% +/- 5%) from the time of second random assignment was higher for cis-RA than for no further therapy, though it was not significant. Overall survival (OS) was significantly higher for each random assignment by a test of the log(-log(.)) transformation of the survival estimates at 5 years (P < .01). The 5-year OS from the second random assignment of patients who underwent both random assignments and who were assigned to ABMT/cis-RA was 59% +/- 8%; for ABMT/no cis-RA, it was 41% +/- 8% [corrected]; for continuing chemotherapy/cis-RA, it was 38% +/- 7%; and for chemotherapy/no cis-RA, it was 36% +/- 7%.Myeloablative therapy and autologous hematopoietic cell rescue result in significantly better 5-year EFS than nonmyeloablative chemo therapy; neither myeloablative therapy with [corrected] autologous hematopoietic cell rescue nor cis-RA given after consolidation therapy significantly improved OS.