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.
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: L
authors.identifier: 0000000235595644
authors.initials: L
authors.lastname: Chilton
authors.affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, UK.
authors.forename: G
authors.initials: G
authors.lastname: Buck
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Harrison
authors.affiliation: Department of Cytogenetics, Mayo Clinic, Rochester, MN, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Ketterling
authors.affiliation: Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: J M
authors.initials: JM
authors.lastname: Rowe
authors.affiliation: Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Tallman
authors.affiliation: Department of Haematology, University College Hospital London, London, UK.
authors.forename: A H
authors.initials: AH
authors.lastname: Goldstone
authors.affiliation: Department of Haematology, Royal Free and University College of London Medical School, London, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Fielding
authors.affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A V
authors.initials: AV
authors.lastname: Moorman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000782:Aneuploidy; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D012008:Recurrence; D055815:Young Adult