This subsection does not discuss infants as a prognostic group. For information about infants with acute lymphoblastic leukemia, refer to the Postinduction Treatment for Specific ALL Subgroups section of this summary.
Former CCG studies made an initial risk assignment of patients older than 1 year as standard risk or high risk based on the NCI consensus age and WBC criteria, regardless of phenotype. The standard-risk category included patients aged 1 to 9 years who had a WBC count at diagnosis less than 50,000/�L. The remaining patients were classified as high risk. Final treatment assignment for CCG protocols was based on early response to therapy with slow early responders being treated as high-risk patients.
Former POG studies defined the low-risk group based on the NCI consensus age and WBC criteria and required the absence of adverse translocations, absence of CNS disease and testicular disease, and the presence of either the ETV6-RUNX1 translocation or trisomy of chromosomes 4 and 10. The high-risk group required the absence of favorable translocations and the presence of CNS or testicular leukemia, or the presence of MLL gene rearrangement, or unfavorable age and WBC count. The standard-risk category included patients not meeting the criteria for inclusion in any of the other risk group categories. In POG studies, patients with T-cell ALL were treated on different protocols than patients with precursor B-cell ALL.
The very high-risk category for CCG and POG was defined by one of the following factors taking precedence over all other considerations: presence of the t(9;22), M3 marrow on day 29 or M2 or M3 marrow on day 43, or hypodiploidy (DNA index <0.95).
Since 2000, risk stratification on BFM protocols has been based almost solely on treatment response criteria. In addition to prednisone prophase response, treatment response is assessed via MRD measurements at two time points, end induction (week 5) and end consolidation (week 12). Patients who are MRD negative at both time points are classified as standard risk, those who have positive MRD at week 5 and low MRD (<10-3) at week 12 are considered intermediate risk, and those with high MRD (?10-3) at week 12 are high risk. Patients with a poor response to the prednisone prophase are also considered high risk, regardless of subsequent MRD. Phenotype, leukemic cell mass estimate, also known as BFM risk factor, and CNS status at diagnosis do not factor into the current risk classification schema. However, patients with either the t(9;22) or the t(4;11) are considered high risk, regardless of early response measures.
Prognostic groups under clinical evaluation
A large, retrospective analysis of CCG and POG data led to the development of a new classification system for the COG. Based on this analysis, patients with precursor B-cell ALL are initially assigned to a standard-risk or high-risk group based on age and initial WBC count. Patients aged 1 to 9.99 years with less than 50,000 WBC/�L are considered standard risk. All children with T-cell phenotype are considered high risk regardless of age and initial WBC count and are treated on a T-cell specific clinical trial. The COG has recently developed a new classification system for precursor-B ALL.