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Blood, 1 February 2007, Vol. 109, No. 3, pp. 926-935.
Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2006-01-024729.
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Submitted January 24, 2006
Accepted September 10, 2006
Risk and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG)
Kirk R. Schultz*, D. Jeanette Pullen, Harland N. Sather, Jonathan J. Shuster, Meenakshi Devidas, Michael J. Borowitz, Andrew J. Carroll, Nyla A. Heerema, Jeffrey E. Rubnitz, Mignon L. Loh, Elizabeth A. Raetz, Naomi J. Winick, Stephen P. Hunger, William L. Carroll, Paul S. Gaynon, and Bruce M. Camitta
Children's Oncology Group Department of Pediatrics, University of British Columbia, Vancouver, BC
Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS
Department of Preventative Medicine, University of Southern California, Los Angeles, CA
Department of Epidemiology & Health Policy Research, University of Florida, Gainesville, FL
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL
Department of Pathology, Division of Clinical Pathology, The Ohio State University, Columbus, OH
Oncology, St. Jude Children's Research Hospital Memphis, Memphis, TN
Department of Pediatrics, UCSF School of Medicine, San Francisco, CA
Department of Pediatrics, NYU Medical Center, New York, NY
UT Southwestern Medical Center, Dallas, TX
Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL
Department of Hematology-Oncology, Children's Hospital, Los Angeles, CA
Department of Pediatrics, Medical College of Wisconsin and Children's Hospital of Wisconsin, WI
* Corresponding author; email: kschultz{at}interchange.ubc.ca.
The Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) joined to form the Children's Oncology Group (COG), in 2000. This merger allowed analysis of clinical, biological, and early response data predictive of event-free survival (EFS) in acute lymphoblastic leukemia (ALL) to develop a new classification system and treatment algorithm. From 11,779 children (1 to 21.99 years) with newly diagnosed B-precursor ALL consecutively enrolled by the CCG (December 1988 to August 1995, N = 4986) and POG (January 1986 to November 1999, N = 6793), we retrospectively analyzed 6238 patients (CCG 1182, POG 5056) with informative cytogenetic data. Four risk groups were defined as very high risk (VHR, 5-year EFS  45%), lower risk (5-year EFS  85%) and standard and high risk as those remaining in the respective NCI risk groups. VHR criteria included extreme hypodiploidy (<44 chromosomes), t(9;22) and/or BCR-ABL, and induction failure. Lower risk patients were NCI standard risk with either t(12;21) (TEL-AML1) or simultaneous trisomies of chromosomes 4, 10, and 17. Even with treatment differences, there was high concordance between the CCG and POG analyses. The COG risk classification scheme is being used for division of B-precursor ALL into lower (27%), standard (32%), high (37%), and VHR (4%) risk groups based on age, WBC, cytogenetics, day 14 marrow response and end induction MRD by flow cytometry in COG trials.
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