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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2756-2762.
Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2003-04-1128.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia
Anthony V. Moorman,
Sue M. Richards,
Mary Martineau,
Kan Luk Cheung,
Hazel M. Robinson,
G. Reza Jalali,
Zoë J. Broadfield,
Rachel L. Harris,
Kerry E. Taylor,
Brenda E. S. Gibson,
Ian M. Hann,
Frank G. H. Hill,
Sally E. Kinsey,
Tim O. B. Eden,
Christopher D. Mitchell, and
Christine J. Harrison, for the United Kingdom Medical Research Council's Childhood Leukaemia Working Party
From the Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, United Kingdom; Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom; Yorkhill National Health Service (NHS) Trust, Glasgow, United Kingdom; Great Ormond Street Hospital, London, United Kingdom; Birmingham Children's Hospital NHS Trust, Birmingham, United Kingdom; St James Hospital, Leeds, United Kingdom; Central Manchester and Manchester Children's University Hospitals Trust, Manchester, United Kingdom; and John Radcliffe Hospital, Oxford, United Kingdom.
High hyperdiploidy (HeH) (51 to 65 chromosomes) is found in one third of children with acute lymphoblastic leukemia and is associated with a good prognosis. Cytogenetic features may further refine this prognosis and identify patients with a poor outcome. We examined the effect of sex, age, individual trisomies, modal number, and structural abnormalities on survival among 700 children with HeH. Univariate analysis showed that age. sex, +4, +10, +18, and a high modal number were associated with survival. Multivariate analysis however, revealed that only age, sex, +4, and +18 were independent indicators. Hazard scores for predicting relapse and mortality were constructed. Three risk groups with 5-year event-free survival (EFS) rates of 86%, 75%, and 50% (P < .0001) were identified. The high-risk group comprised boys older than 9 years, boys aged 1 through 9 years without +18, and girls older than 9 years without +18, while girls aged 1 through 9 years with +18 had the best EFS. In terms of mortality, those younger than age 10 years with both +4 and +18 had an improved survival (96% vs 84% at 5 years, P < .0001). These findings confirm that the outcome of children with HeH is heterogeneous and that specific trisomies can identify patients with the greatest and least risk of treatment failure.
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