Genetic and Response-Based Risk Classification Identifies a Subgroup of NCI High Risk Childhood B-Lymphoblastic Leukemia (HR B-ALL) with Outstanding Outcomes: A Report from the Children's Oncology Group (COG)

[Graphic][1] Overall improvements in ALL outcomes have been attributed in part to refinements in risk classification that affect treatment intensity. The COGdeveloped a real-time disease classification protocol utilizing clinical, biologic and early disease response measures from local and central reference laboratories. Patients between 1-30 years were enrolled on the COG AALL03B1 classification study at the time of B-ALL diagnosis and subsequently initiated a 3-drug (standard risk; SR) or 4-drug induction (HR) based on NCI risk group. All patients underwent standardized testing at approved or central laboratories to detect favorable (triple trisomies of chromosomes 4, 10 and 17 [TT] or ETV6-RUNX1 fusion) and unfavorable (hypodiploidy [DNA index 1 year of age with B-ALL were classified into low, standard, high or very high risk groups for treatment allocation. Variables used for risk classification included age, initial WBC, extramedullary disease status, blast cytogenetics and early treatment response based on bone marrow morphology and day 29 marrow minimal residual disease (MRD). Rapid early response (RER) was defined as M1 (