Originally published as JCO Early Release 10.1200/JCO.2005.05.582 on August 22 2005

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Hyperdiploidy Plus Nonamplified MYCN Confers a Favorable Prognosis in Children 12 to 18 Months Old With Disseminated Neuroblastoma: A Pediatric Oncology Group Study

From the Dana-Farber Cancer Institute, Harvard Medical School; Pediatric Hematology/Oncology, Boston Floating Hospital for Infants & Children, Boston, MA; Children's Oncology Group, University of Florida, Gainesville, FL; Northwestern University, Feinberg School of Medicine, Chicago, IL; Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA; University of Alabama at Birmingham, Birmingham, AL

Address reprint requests to Rani E. George, MD, PhD, MRCP, Department of Pediatric Hematology and Oncology, Dana 322, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: rani_george{at}dfci.harvard.edu

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.

Supported in part by National Institutes of Health grant No. CA-39771 (GMB) and by the POG Statistics and Data Center grants No. U10 CA29139, CA25408, and the POG Chair's grant No. U10 CA30969. R.E.G. is supported by the National Institute for Neurological Diseases and Stroke grant No. K08NS047983, Young Investigator Awards from the American Society of Clinical Oncology, the Children's Oncology Group, and the Fred Lovejoy Resident Research Award.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2003, Chicago, IL.

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

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