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

• Published in: Journal of clinical oncology Vol. 27; no. 7; pp. 1007 - 1013
• Main Authors: MATTHAY, Katherine K, REYNOLDS, C. Patrick, SEEGER, Robert C, SHIMADA, Hiroyuki, ADKINS, E. Stanton, HAAS-KOGAN, Daphne, GERBING, Robert B, LONDON, Wendy B, VILLABLANCA, Judith G
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.03.2009
• Subjects: Adolescent; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Humans; Infant; Isotretinoin - therapeutic use; Medical sciences; Neuroblastoma - pathology; Neuroblastoma - therapy; Neurology; Original Reports; Survival Analysis; Tumors; Tumors of the nervous system. Phacomatoses; Whole-Body Irradiation; Human; High risk; Nervous system diseases; Retinoid; Neuroblastoma; Malignant tumor; Long term; Randomization; Cancerology; Treatment; Clinical trial; Myelosuppression; Isotretinoin; Autonomic neuropathy; Child; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2007.13.8925

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.