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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1112-1115.
Prepublished online as a Blood First Edition Paper on May 1, 2007; DOI 10.1182/blood-2006-07-038299.


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CLINICAL TRIALS AND OBSERVATIONS

Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia

James B. Nachman1, Nyla A. Heerema2, Harland Sather3, Bruce Camitta4, Erik Forestier5, Christine J. Harrison6, Nicole Dastugue7, Martin Schrappe8, Ching-Hon Pui9, Giuseppe Basso10, Lewis B. Silverman11, and Gritta E. Janka-Schaub12

1 The University of Chicago Comer Children's Hospital, IL; 2 Columbus Children's Hospital and The Ohio State University, Columbus, OH; 3 Children's Oncology Group–Operations Center, Arcadia, CA; 4 Midwest Children's Cancer Center, Department of Pediatrics of the Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee; 5 Department of Clinical Sciences and Paediatrics, University of Umeå, Umeå, Sweden; 6 Leukaemia Research Cytogenetics Group, Cancer Sciences Divison, University of Southampton, Southampton, United Kingdom; 7 Génétique des Hémopathies, Laboratoire d'Hématologie, Hôpital Purpan, Toulouse, France; 8 University Hospital Schwanenweg, Department of Pediatrics, Kiel, Germany; 9 St Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis; 10 Pediatrics Department, University of Padova, Padova, Italy; 11 Department of Pediatric Oncology, Dana-Farber Cancer Institute and Division of Hematology Oncology, Children's Hospital, Boston, MA; 12 Children's University Hospital, Department of Pediatric Hematology and Oncology, University of Hamburg, Hamburg, Germany

One-hundred thirty-nine patients with acute lymphoblastic leukemia (ALL) and hypodiploidy (fewer than 45 chromosomes) were collected from 10 different national ALL study groups and single institutions. Patients were stratified by modal chromosome number into 4 groups: 24 to 29 (N = 46); 33 to 39 (N = 26); 40 to 43 (N = 13); and 44 (N = 54) chromosomes. Nine patients were Philadelphia chromosome (Ph) positive (4 cases: 44 chromosomes; 5 cases: 40-43 chromosomes) and were not considered further. Event-free survival (EFS) and overall survival (OS) of the remaining 130 patients were 38.5% ± 4.4% and 49.8% ± 4.2% at 8 years, respectively. There were no significant differences in outcome between patients with 24 to 29, 33 to 39, or 40 to 43 chromosomes. Compared with patients with fewer than 44 chromosomes, patients with 44 chromosomes had a significantly better EFS (P = .01; 8-year estimate, 52.2% vs 30.1%) and OS (P = .017; 69% vs 37.5%). For patients with 44 chromosomes, monosomy 7, the presence of a dicentric chromosome, or both predicted a worse EFS but similar OS. Doubling of the hypodiploid clone occurred in 32 patients (24-29 chromosomes [n = 25] and 33-39 chromosomes [n = 7]) and had no prognostic implication. Children and adolescents with ALL and hypodiploidy with fewer than 44 chromosomes have a poor outcome despite contemporary therapy.


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M. Arico, M. G. Valsecchi, C. Rizzari, E. Barisone, A. Biondi, F. Casale, F. Locatelli, L. Lo Nigro, M. Luciani, C. Messina, et al.
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