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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3189-3197.
Prepublished online as a Blood First Edition Paper on December 14, 2006; DOI 10.1182/blood-2006-10-051912.
 Previous Article | Next Article 
Submitted October 13, 2006
Accepted December 5, 2006
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
Anthony V Moorman*, Christine J Harrison, Georgina AN Buck, Sue M Richards, Lorna M Secker-Walker, Mary Martineau, Gail H Vance, Athena M Cherry, Rodney R Higgins, Adele K Fielding, Letizia Foroni, Elisabeth Paietta, Martin S Tallman, Mark R Litzow, Peter H Wiernik, Jacob M Rowe, Anthony H Goldstone, and Gordon W Dewald
Leukaemia Research Cytogenics Group, Cancer Sciences Div., University of Southampton, Southampton, United Kingdom
Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom
Emeritus, c/o Leukaemia Research Cytogenics Group, c/o University of Southampton, Southampton, United Kingdom
Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
Pathology, Stanford University School of Medicine, Stanford, CA, United States
Allina Medical Laboratories, Abbott Northwestern Hospital, Minneapolis, MN, United States
Department of Haematology, Royal Free and UCMS, London, United Kingdom
Comprehensive Cancer Center, Our Lady of Mercy Medical Center, New York, NY, United States
Division of Hematology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
Division of Hematology, Mayo Clinic, Rochester, MN, United States
Department of Hematology, Rambam Medical Center, Haifa, Israel
Department of Haematology, UCLH, London, United Kingdom
Division of Laboratory Genetics, Mayo Clinic, Rochester, MN, United States
* Corresponding author; email: avm{at}soton.ac.uk.
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.
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