Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: A Pediatric Oncology Group study

Abstract

Purpose: To determine predictive strength of tumor cell ploidy and MYCN gene amplification on survival of children older than 12 months with disseminated neuroblastoma (NB). Patients and Methods: Of 648 children with stage D NB enrolled onto the Pediatric Oncology Group NB Biology Study 9047 (1990-2000), 560 children were assessable for ploidy and MYCN amplification. Treatment of patients older than 12 months varied; most receiving high-dose chemotherapy with stem-cell rescue. Infants received standard chemotherapy, depending on MYCN status and ploidy. Results: Among stage D MYCN-amplified patients, 4-year event-free survival (EFS) ± SE had no prognostic significance for tumor cell ploidy for patients either younger than 12 months or ≥ 12 months old. However, among stage D nonamplified-MYCN patients, 4-year EFS for those with tumor hyperdiploidy (DNA index [DI] > 1) was clearly superior to those with diploidy (DI < 1): younger than 12 months, 83.7% ± 4.4% (n = 87) versus 46.2% ± 13.8% (n = 13; P= .0003); and for 12- to 24-month-old children, 72.7% ± 10.2% (n = 22) versus 26.7% ± 13.2% (n = 16; P = .0092). Further analysis suggested better prognoses in the 12- to 18-month-old subgroup with hyperdiploid tumors (4-year EFS, 92.9% ± 7.2%) compared with the 19-to 24-month-old subgroup (4-year EFS, 37.5% ± 21.0%; P = .0037). In children older than 24 months, outcome was dire (< 20% long-term survival), regardless of ploidy or MYCN status. Conclusion: Children 12 to 18 months old with metastatic NB had favorable outcomes with high-dose therapy if their tumors were hyperdiploid and lacked MYCN amplification. This subgroup may respond well to contemporary chemotherapy, and could be spared intensive myeloablative therapy with stem-cell rescue. © 2005 by American Society of Clinical Oncology.