Trisomy of Leukemic Cell Chromosomes 4 and 10 Identifies Children With B-Progenitor Cell Acute Lymphoblastic Leukemia With a Very Low Risk of Treatment Failure: A Pediatric Oncology Group Study

• Published in: Blood 1992-06, Vol.79 (12), p.3316-3324
• Main Authors: Harris, Michael B., Shuster, Jonathan J., Carroll, Andrew, Look, A. Thomas, Borowitz, Michael J., Crist, William M., Nitschke, Ruprecht, Pullen, Jeanette, Steuber, C. Philip, Land, Vita J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Burkitt Lymphoma - genetics; Child; Child, Preschool; Chromosomes, Human, Pair 10; Chromosomes, Human, Pair 4; Humans; Infant; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Prognosis; Remission Induction; Trisomy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V79.12.3316.3316

To account for the superior prognosis of hyperdiploid, B-progenitor acute lymphoblastic leukemia (ALL), we investigated the influence of trisomy in 1021 children greater than or equal to 1 year old by recursive partitioning analysis. The patients were treated according to a stratified, randomized study testing antimetabolite-based therapies. Trisomies of several individual chromosomes were associated with a better prognosis in a univariate statistical analysis. Of greater importance, trisomy of both chromosomes 4 and 10 identified a subgroup of patients (n = 180) with an extremely favorable 4-year event-free survival (EFS). Combined trisomy of chromosomes 4 and 10 retained its prognostic significance after stratification of patients by DNA index, age, and leukocyte count. Among patients with a DNA index greater than 1.16, patients with trisomies of both chromosomes 4 and 10 had a 4-year EFS of 96.6% (n = 161, SE = 3.8%), whereas patients with neither or only one of these trisomies had a 4-year EFS of 70.4% (n = 73, SE = 11.5%). All 19 patients with a DNA index less than or equal to 1.16 but with trisomies of chromosomes 4 and 10 remain in remission, suggesting that favorable chromosome trisomy dominates in a situation in which the cellular DNA content of less than or equal to 1.16 predicts a less favorable outcome. We conclude that combined trisomy of chromosomes 4 and 10 independently predicts EFS among children with B-progenitor ALL. Patients within the B-progenitor group who have this feature (about 20% of those with clonal abnormalities) are likely to be cured with antimetabolite-based chemotherapy--an approach that should produce few significant late effects.