Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII / Eastern Cooperative Oncology Group (ECOG) 2993 Trial

Abstract

Pre-treatment cytogenetics is a known predictor of outcome in haematological malignancies. However, its usefulness in adult acute lymphoblastic leukaemia is generally limited to the presence of the Philadelphia chromosome (Ph); because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1,522 adult patients enrolled on the MRC UKALLXII / ECOG 2993 trial. The incidence and clinical associations for over 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21;q23), t(8;14)(q24.1;q32), complex karyotype (five or more chromosomal abnormalities) or low hypodiploidy / near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared to other patients. In contrast, patients with high hyperdiploidy or a del(9p) had a significantly improved outcome. Multivariate analysis demonstrated that the prognostic relevance of t(8;14), complex karyotype and Ho-Tr was independent of gender, age, white cell count and T-cell status among Ph negative patients. The observation that Ho-Tr and, for the first time, karyotype complexity confer an increased risk of treatment failure demonstrates that cytogenetic subgroups other than the Ph can and should be used to risk stratify adults with ALL in future trials