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George, R.E. et al.

George, London, Cohn, Maris, Kretschmar, Diller, Brodeur, Castleberry, Look,

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

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 > 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 < or = 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.[1]

References

Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study. George, R.E., London, W.B., Cohn, S.L., Maris, J.M., Kretschmar, C., Diller, L., Brodeur, G.M., Castleberry, R.P., Look, A.T. J. Clin. Oncol. (2005) [Pubmed]

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