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

Michael B. Harris, Jonathan J. Shuster, Andrew Carroll, A. Thomas Look, Michael J Borowitz, William M. Crist, Ruprecht Nitschke, Jeanette Pullen, C. Philip Steuber, Vita J. Land

Research output: Contribution to journalArticle

Abstract

To account for the superior prognosis of hyperdiploid, B-progenitor acute lymphoblastic leukemia (ALL), we investigated the influence of trisomy in 1021 children ≥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 ≤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 ≤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.

Original languageEnglish (US)
Pages (from-to)3316-3324
Number of pages9
JournalBlood
Volume79
Issue number12
StatePublished - Jun 15 1992
Externally publishedYes

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Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 4
Pediatrics
B-Lymphoid Precursor Cells
Oncology
Trisomy
Chromosomes
Treatment Failure
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Disease-Free Survival
Antimetabolites
DNA
Chemotherapy
Polyploidy
Statistical methods
Leukocyte Count
Testing
Drug Therapy

ASJC Scopus subject areas

  • Hematology

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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. / 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.

In: Blood, Vol. 79, No. 12, 15.06.1992, p. 3316-3324.

Research output: Contribution to journalArticle

Harris, MB, Shuster, JJ, Carroll, A, Look, AT, Borowitz, MJ, Crist, WM, Nitschke, R, Pullen, J, Steuber, CP & Land, VJ 1992, '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', Blood, vol. 79, no. 12, pp. 3316-3324.
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. / 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. In: Blood. 1992 ; Vol. 79, No. 12. pp. 3316-3324.
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abstract = "To account for the superior prognosis of hyperdiploid, B-progenitor acute lymphoblastic leukemia (ALL), we investigated the influence of trisomy in 1021 children ≥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 ≤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 ≤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.",
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T1 - 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

T2 - A pediatric oncology group study

AU - Harris, Michael B.

AU - Shuster, Jonathan J.

AU - Carroll, Andrew

AU - Look, A. Thomas

AU - Borowitz, Michael J

AU - Crist, William M.

AU - Nitschke, Ruprecht

AU - Pullen, Jeanette

AU - Steuber, C. Philip

AU - Land, Vita J.

PY - 1992/6/15

Y1 - 1992/6/15

N2 - To account for the superior prognosis of hyperdiploid, B-progenitor acute lymphoblastic leukemia (ALL), we investigated the influence of trisomy in 1021 children ≥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 ≤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 ≤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.

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