Philadelphia chromosome-negative very high-risk acute lymphoblastic leukemia in children and adolescents: results from Children’s Oncology Group Study AALL0031

Purpose To examine population-based improvements in survival and the impact of clinical covariates on outcome among children and adolescents with acute lymphoblastic leukemia (ALL) enrolled onto Children's Oncology Group (COG) clinical trials between 1990 and 2005. Patients and Methods In total, 21,626 persons age 0 to 22 years were enrolled onto COG ALL clinical trials from 1990 to 2005, representing 55.8% of ALL cases estimated to occur among US persons younger than age 20 years during this period. This period was divided into three eras (1990-1994, 1995-1999, and 2000-2005) that included similar patient numbers to examine changes in 5- and 10-year survival over time and the relationship of those changes in survival to clinical covariates, with additional analyses of cause of death. Results Five-year survival rates increased from 83.7% in 1990-1994 to 90.4% in 2000-2005 (P < .001). Survival improved significantly in all subgroups (except for infants age ≤ 1 year), including males and females; those age 1 to 9 years, 10+ years, or 15+ years; in whites, blacks, and other races; in Hispanics, non-Hispanics, and patients of unknown ethnicity; in those with B-cell or T-cell immunophenotype; and in those with National Cancer Institute (NCI) standard- or high-risk clinical features. Survival rates for infants changed little, but death following relapse/disease progression decreased and death related to toxicity increased. Conclusion This study documents ongoing survival improvements for children and adolescents with ALL. Thirty-six percent of deaths occurred among children with NCI standard-risk features emphasizing that efforts to further improve survival must be directed at both high-risk subsets and at those children predicted to have an excellent chance for cure.

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Gene Expression Signatures Predictive of Early Response and Outcome in High-Risk Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

Yearbook of Oncology ◽

10.1016/s1040-1741(09)79350-9 ◽

2009 ◽

Vol 2009 ◽

pp. 198-199

Author(s):

R.J. Arceci

Keyword(s):

Gene Expression ◽

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Lymphoblastic Leukemia ◽

Early Response ◽

Childhood Acute Lymphoblastic Leukemia ◽

Oncology Group ◽

Oncology Group Study ◽

Gene Expression Signatures

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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)

Blood ◽

10.1182/blood-2006-01-024729 ◽

2006 ◽

Vol 109 (3) ◽

pp. 926-935 ◽

Cited By ~ 283

Author(s):

Kirk R. Schultz ◽

D. Jeanette Pullen ◽

Harland N. Sather ◽

Jonathan J. Shuster ◽

Meenakshi Devidas ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Pediatric Oncology ◽

Lower Risk ◽

Lymphoblastic Leukemia ◽

Risk Groups ◽

Oncology Group ◽

Cancer Group ◽

Pediatric Oncology Group ◽

Very High

Abstract 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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Development and Refinement of Augmented Treatment Regimens for Pediatric High-Risk Acute Lymphoblastic Leukemia

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2012.32.180 ◽

2012 ◽

pp. 611-615

Author(s):

Stephen P. Hunger

Keyword(s):

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Children And Adolescents ◽

Western Europe ◽

Randomized Clinical Trials ◽

Kinase Inhibitor ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Cooperative Groups ◽

Treatment Regimens

Overview: The 5-year survival rate for children and adolescents with acute lymphoblastic leukemia (ALL) is now at least 90%. However, clinical features (age and initial white blood cell count [WBC]), early treatment response, and the presence/absence of specific sentinel genomic lesions can identify subsets of high-risk (HR) ALL patients with a much higher risk of treatment failure. Chemotherapy regimens used to treat HR ALL have been refined over the past 3 decades through randomized clinical trials conducted by the Children's Oncology Group (COG) in North America and the Berlin-Frankfurt-Muenster (BFM) group in Western Europe. Contemporary COG HR ALL treatment regimens were developed from the BFM-76 regimen, with subsequent changes that led to development and refinement of a so-called augmented BFM (ABFM) regimen used today. Although contemporary COG and BFM treatment regimens are not identical, there are many more similarities than differences. With improvements in survival, it has become clear that although the outcome of some patients with HR ALL can be improved by optimizing use of standard cytotoxic chemotherapy agents, this approach has had only limited success for other patient subsets. In contrast, introduction of the tyrosine kinase inhibitor imatinib has led to dramatic outcome improvements for children and adolescents with Philadelphia chromosome–positive ALL. Genomic studies are identifying new sentinel genomic lesions that can serve as potential therapeutic targets, which will likely lead to the testing of novel and/or targeted therapies in more children with HR ALL. Such studies will require increased collaboration between Western European and North American cooperative groups.

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