High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL)

Cytogenetic features, clinical characteristics and outcome

L. Chilton, G. Buck, C. J. Harrison, R. P. Ketterling, J. M. Rowe, M. S. Tallman, A. H. Goldstone, A. K. Fielding, A. V. Moorman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

High hyperdiploidy (HeH, 51-65 chromosomes) is an established genetic subtype of acute lymphoblastic leukaemia (ALL). The clinical and cytogenetic features as well as outcome of HeH among adolescents and adults have not been thoroughly investigated. Among 1232 B-cell precursor ALL patients (15-65 years) treated in the UKALLXII/ECOG2993 trial, 160 (13%) had a HeH karyotype, including 80 patients aged >24 years. The frequency of HeH was the same in Philadelphia chromosome (Ph)-positive and-negative cases, but Ph-positive patients were older. The cytogenetic profiles of Ph-positive and Ph-negative HeH cases were similar, although trisomy 2 was strongly associated with Ph-positive HeH. Overall, Ph-positive HeH patients did not have an inferior overall survival compared with Ph-negative patients (P=0.2: 50 vs 57% at 5 years). Trisomy of chromosome 4 was associated with a superior outcome in Ph-negative patients, whereas +5 and +20 were associated with an inferior outcome in Ph-positive and Ph-negative patients, respectively. All three markers retained significance in multivariate analysis adjusting for age and white cell count: hazard ratio for risk of death 0.47 (95% CI: 0.27-0.84) (P=0.01), 3.73 (1.51-9.21) (P=0.004) and 2.63 (1.25-5.54) (P=0.01), respectively. In conclusion, HeH is an important subtype of ALL at all ages and displays outcome heterogeneity according to chromosomal gain.

Original languageEnglish (US)
Pages (from-to)1511-1518
Number of pages8
JournalLeukemia
Volume28
Issue number7
DOIs
StatePublished - 2014

Fingerprint

Polyploidy
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cytogenetics
Trisomy
Philadelphia Chromosome
Chromosomes, Human, Pair 4
B-Lymphoid Precursor Cells
Karyotype
Multivariate Analysis
Cell Count
Chromosomes
Odds Ratio

Keywords

  • acute lymphoblastic leukaemia
  • adolescents
  • adults
  • chromosomal abnormalities
  • high hyperdiploidy
  • prognosis

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Chilton, L., Buck, G., Harrison, C. J., Ketterling, R. P., Rowe, J. M., Tallman, M. S., ... Moorman, A. V. (2014). High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): Cytogenetic features, clinical characteristics and outcome. Leukemia, 28(7), 1511-1518. https://doi.org/10.1038/leu.2013.379

High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL) : Cytogenetic features, clinical characteristics and outcome. / Chilton, L.; Buck, G.; Harrison, C. J.; Ketterling, R. P.; Rowe, J. M.; Tallman, M. S.; Goldstone, A. H.; Fielding, A. K.; Moorman, A. V.

In: Leukemia, Vol. 28, No. 7, 2014, p. 1511-1518.

Research output: Contribution to journalArticle

Chilton, L, Buck, G, Harrison, CJ, Ketterling, RP, Rowe, JM, Tallman, MS, Goldstone, AH, Fielding, AK & Moorman, AV 2014, 'High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): Cytogenetic features, clinical characteristics and outcome', Leukemia, vol. 28, no. 7, pp. 1511-1518. https://doi.org/10.1038/leu.2013.379
Chilton, L. ; Buck, G. ; Harrison, C. J. ; Ketterling, R. P. ; Rowe, J. M. ; Tallman, M. S. ; Goldstone, A. H. ; Fielding, A. K. ; Moorman, A. V. / High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL) : Cytogenetic features, clinical characteristics and outcome. In: Leukemia. 2014 ; Vol. 28, No. 7. pp. 1511-1518.
@article{90193987e433417f8331de9b137b233e,
title = "High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): Cytogenetic features, clinical characteristics and outcome",
abstract = "High hyperdiploidy (HeH, 51-65 chromosomes) is an established genetic subtype of acute lymphoblastic leukaemia (ALL). The clinical and cytogenetic features as well as outcome of HeH among adolescents and adults have not been thoroughly investigated. Among 1232 B-cell precursor ALL patients (15-65 years) treated in the UKALLXII/ECOG2993 trial, 160 (13{\%}) had a HeH karyotype, including 80 patients aged >24 years. The frequency of HeH was the same in Philadelphia chromosome (Ph)-positive and-negative cases, but Ph-positive patients were older. The cytogenetic profiles of Ph-positive and Ph-negative HeH cases were similar, although trisomy 2 was strongly associated with Ph-positive HeH. Overall, Ph-positive HeH patients did not have an inferior overall survival compared with Ph-negative patients (P=0.2: 50 vs 57{\%} at 5 years). Trisomy of chromosome 4 was associated with a superior outcome in Ph-negative patients, whereas +5 and +20 were associated with an inferior outcome in Ph-positive and Ph-negative patients, respectively. All three markers retained significance in multivariate analysis adjusting for age and white cell count: hazard ratio for risk of death 0.47 (95{\%} CI: 0.27-0.84) (P=0.01), 3.73 (1.51-9.21) (P=0.004) and 2.63 (1.25-5.54) (P=0.01), respectively. In conclusion, HeH is an important subtype of ALL at all ages and displays outcome heterogeneity according to chromosomal gain.",
keywords = "acute lymphoblastic leukaemia, adolescents, adults, chromosomal abnormalities, high hyperdiploidy, prognosis",
author = "L. Chilton and G. Buck and Harrison, {C. J.} and Ketterling, {R. P.} and Rowe, {J. M.} and Tallman, {M. S.} and Goldstone, {A. H.} and Fielding, {A. K.} and Moorman, {A. V.}",
year = "2014",
doi = "10.1038/leu.2013.379",
language = "English (US)",
volume = "28",
pages = "1511--1518",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL)

T2 - Cytogenetic features, clinical characteristics and outcome

AU - Chilton, L.

AU - Buck, G.

AU - Harrison, C. J.

AU - Ketterling, R. P.

AU - Rowe, J. M.

AU - Tallman, M. S.

AU - Goldstone, A. H.

AU - Fielding, A. K.

AU - Moorman, A. V.

PY - 2014

Y1 - 2014

N2 - High hyperdiploidy (HeH, 51-65 chromosomes) is an established genetic subtype of acute lymphoblastic leukaemia (ALL). The clinical and cytogenetic features as well as outcome of HeH among adolescents and adults have not been thoroughly investigated. Among 1232 B-cell precursor ALL patients (15-65 years) treated in the UKALLXII/ECOG2993 trial, 160 (13%) had a HeH karyotype, including 80 patients aged >24 years. The frequency of HeH was the same in Philadelphia chromosome (Ph)-positive and-negative cases, but Ph-positive patients were older. The cytogenetic profiles of Ph-positive and Ph-negative HeH cases were similar, although trisomy 2 was strongly associated with Ph-positive HeH. Overall, Ph-positive HeH patients did not have an inferior overall survival compared with Ph-negative patients (P=0.2: 50 vs 57% at 5 years). Trisomy of chromosome 4 was associated with a superior outcome in Ph-negative patients, whereas +5 and +20 were associated with an inferior outcome in Ph-positive and Ph-negative patients, respectively. All three markers retained significance in multivariate analysis adjusting for age and white cell count: hazard ratio for risk of death 0.47 (95% CI: 0.27-0.84) (P=0.01), 3.73 (1.51-9.21) (P=0.004) and 2.63 (1.25-5.54) (P=0.01), respectively. In conclusion, HeH is an important subtype of ALL at all ages and displays outcome heterogeneity according to chromosomal gain.

AB - High hyperdiploidy (HeH, 51-65 chromosomes) is an established genetic subtype of acute lymphoblastic leukaemia (ALL). The clinical and cytogenetic features as well as outcome of HeH among adolescents and adults have not been thoroughly investigated. Among 1232 B-cell precursor ALL patients (15-65 years) treated in the UKALLXII/ECOG2993 trial, 160 (13%) had a HeH karyotype, including 80 patients aged >24 years. The frequency of HeH was the same in Philadelphia chromosome (Ph)-positive and-negative cases, but Ph-positive patients were older. The cytogenetic profiles of Ph-positive and Ph-negative HeH cases were similar, although trisomy 2 was strongly associated with Ph-positive HeH. Overall, Ph-positive HeH patients did not have an inferior overall survival compared with Ph-negative patients (P=0.2: 50 vs 57% at 5 years). Trisomy of chromosome 4 was associated with a superior outcome in Ph-negative patients, whereas +5 and +20 were associated with an inferior outcome in Ph-positive and Ph-negative patients, respectively. All three markers retained significance in multivariate analysis adjusting for age and white cell count: hazard ratio for risk of death 0.47 (95% CI: 0.27-0.84) (P=0.01), 3.73 (1.51-9.21) (P=0.004) and 2.63 (1.25-5.54) (P=0.01), respectively. In conclusion, HeH is an important subtype of ALL at all ages and displays outcome heterogeneity according to chromosomal gain.

KW - acute lymphoblastic leukaemia

KW - adolescents

KW - adults

KW - chromosomal abnormalities

KW - high hyperdiploidy

KW - prognosis

UR - http://www.scopus.com/inward/record.url?scp=84904054301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904054301&partnerID=8YFLogxK

U2 - 10.1038/leu.2013.379

DO - 10.1038/leu.2013.379

M3 - Article

VL - 28

SP - 1511

EP - 1518

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 7

ER -