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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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CLINICAL TRIALS AND OBSERVATIONS
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. Schultz1,
D. Jeanette Pullen2,
Harland N. Sather3,
Jonathan J. Shuster4,
Meenakshi Devidas4,
Michael J. Borowitz5,
Andrew J. Carroll6,
Nyla A. Heerema7,
Jeffrey E. Rubnitz8,
Mignon L. Loh9,
Elizabeth A. Raetz10,
Naomi J. Winick11,
Stephen P. Hunger12,
William L. Carroll10,
Paul S. Gaynon13, and
Bruce M. Camitta14
1 Children's Oncology Group, Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplantation, BC Children's Hospital, University of British Columbia, Vancouver, Canada;
2 Department of Pediatrics, University of Mississippi Medical Center, Jackson;
3 Department of Preventative Medicine, University of Southern California, Los Angeles;
4 Children's Oncology Group Statistics and Data Center and the University of Florida, Department of Epidemiology and Health Policy Research, Gainesville;
5 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD;
6 Department of Genetics, University of Alabama at Birmingham;
7 Division of Clinical Pathology, Department of Pathology, The Ohio State University, Columbus;
8 Oncology, St Jude Children's Research Hospital, Memphis, TN;
9 Department of Pediatrics, University of California San Francisco School of Medicine;
10 Department of Pediatrics, New York University Medical Center, New York;
11 University of Texas Southwestern Medical Center, Dallas;
12 Department of Pediatrics and University of Florida Shands Cancer Center, University of Florida College of Medicine, Gainesville;
13 Department of Hematology-Oncology, Children's Hospital, Los Angeles, CA;
14 Midwest Children's Cancer Center, Department of Pediatrics, Medical College of Wisconsin and Children's Hospital of Wisconsin
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, biologic, 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 (age, 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% or below), lower risk (5-year EFS, at least 85%), and standard and high risk (those remaining in the respective National Cancer Institute [NCI] risk groups). VHR criteria included extreme hypodiploidy (fewer than 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 very-high- (4%) risk groups based on age, white blood cell (WBC) count, cytogenetics, day-14 marrow response, and end induction minimal residual disease (MRD) by flow cytometry in COG trials.
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