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.

Frequency of Chromosomal Abnormalities in Pakistani Adults with Acute Lymphoblastic Leukemia

“…Hyperdiploidy (47-57 chromosomes) which carry good prognosis was observed in 9 patients with B-cell phenotype. Its occurrence in younger age group (15-29 years) in this study is in accordance with the literature (Faderl et al, 2010;Chilton et al, 2013). The difference between 15-19 year and 20-29 year age group was not significant (p=1.0).…”

Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia

“…9,12,13,15 The SNP array analysis identified three additional high hyperdiploid and five additional low hypodiploid cases, showing that this method is frequently more sensitive for detection of aneuploidy than conventional cytogenetic analysis. In line with high hyperdiploid childhood ALL and a recent cytogenetic study on high hyperdiploid adult cases, 16,17 the cases in this study showed frequent gains of chromosomes X, 4, 10, 17, 18 and 21, although the pattern of chromosomal gains was less specific than in pediatric ALL. All low hypodiploid cases had retained heterodisomy for chromosomes X and 21 and lost chromosomes 7 and 17, in line with previous reports.…”

Poor outcomes associated with +der(22)t(9;22) and −9/9p in patients with Philadelphia chromosome‐positive acute lymphoblastic leukemia receiving chemotherapy plus a tyrosine kinase inhibitor

“…We found that HeH was associated with favorable outcomes, even when +der(22)t(9;22) or −9/9p was also present. HeH has been well‐established to be associated with superior survival in adults with ALL, although most studies have primarily evaluated patients with Philadelphia chromosome‐negative disease . Our finding that the negative prognostic influence of +der(22)t(9;22) and −9/9p is restricted to patients without HeH highlights that HeH ALL is a unique clinical entity, including among patients with Ph+ ALL.…”