Introduction to Risk-Based Treatment

Children with acute lymphoblastic leukemia (ALL) are usually treated according to risk groups defined by both clinical and laboratory features. The intensity of treatment required for cure varies substantially among subsets of children with ALL. Risk-based treatment assignment is used in children with ALL so that patients with favorable clinical and biological features who are likely to have a very good outcome with modest therapy can be spared more intensive and toxic treatment, while a more aggressive, potentially more toxic therapeutic approach is reserved for patients with a lower probability of long-term survival.[1,2]

Certain ALL study groups, such as the Children’s Oncology Group (COG), use a more- or less-intensive induction regimen based on a subset of pretreatment factors, while other groups give a similar induction regimen to all patients.

Factors used by the COG to determine the intensity of induction include the following:

The NCI risk group classification for B-ALL stratifies risk according to age and white blood cell (WBC) count, as follows:[3]

All study groups modify the intensity of postinduction therapy on the basis of a variety of prognostic factors, including NCI risk group, immunophenotype, early response determinations, and cytogenetics and genomic alterations.[4] Detection of the BCR::ABL1 fusion (i.e., BCR::ABL1-positive ALL) leads to immediate changes in induction therapy, including the addition of a tyrosine kinase inhibitor, such as imatinib or dasatinib.[5]

Risk-based treatment assignment requires the availability of prognostic factors that reliably predict outcome. For children with ALL, a number of factors have demonstrated prognostic value, some of which are described below.[6] Factors affecting prognosis are grouped into the following three categories:

As in any discussion of prognostic factors, the relative order of significance and the interrelationship of the variables are often treatment dependent and require multivariate analysis to determine which factors operate independently as prognostic variables. Because prognostic factors are treatment dependent, improvements in therapy may diminish or abrogate the significance of any of these prognostic factors.

A subset of the prognostic and clinical factors discussed below is used for the initial stratification of children with ALL for treatment assignment. For brief descriptions of the prognostic groupings currently applied in ongoing clinical trials in the United States, see the Prognostic (risk) groups under clinical evaluation section.

For information about important prognostic factors at relapse, see the Prognostic Factors After First Relapse of Childhood ALL section.