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Leukemia. 2014 Jul;28(7):1511-8. doi: 10.1038/leu.2013.379. Epub 2013 Dec 19.

High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): cytogenetic features, clinical characteristics and outcome.

Author information

1
Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
2
Clinical Trial Service Unit, University of Oxford, Oxford, UK.
3
Department of Cytogenetics, Mayo Clinic, Rochester, MN, USA.
4
Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel.
5
Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
6
Department of Haematology, University College Hospital London, London, UK.
7
Department of Haematology, Royal Free and University College of London Medical School, London, UK.

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.

PMID:
24352198
DOI:
10.1038/leu.2013.379
[Indexed for MEDLINE]

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