Originally published as JCO Early Release 10.1200/JCO.2007.13.8925 on January 26 2009

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

From the University of California at San Francisco School of Medicine, San Francisco, CA; the Childrens Hospital Los Angeles and the University of Southern California Keck School of Medicine; and the Children's Oncology Group Statistics and Data Center, Los Angeles, CA; the South Carolina Cancer Center, Columbia, SC; and the University of Florida and Children's Oncology Group Statistics and Data Center, Gainesville, FL.

Corresponding author: Katherine K. Matthay, MD, University of California School of Medicine, 505 Parnassus Ave, Room M647, San Francisco, CA, 94143-0106; e-mail: matthayk{at}peds.ucsf.edu.

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% ± 7%; for continuing chemotherapy/cis-RA, it was 38% ± 7%; and for chemotherapy/no cis-RA, it was 36% ± 7%.

Conclusion 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.

Supported by Grants No. CA98413 from the Children's Oncology Group and CA13539 from the Children's Cancer Group, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by the Kasle and Tcalcevik Neuroblastoma Research fund (K.K.M.), the Campini Foundation (K.K.M.), and the Conner fund (K.K.M.), and by Grants No. CA82830 and CA81403 from the National Cancer Institute (C.P.R.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

The initial results of this trial were previously published in the New England Journal of Medicine 341:1165-1173, 1999.

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