Cancer Health Center

Treatment of childhood acute lymphoblastic leukemia (ALL) typically involves chemotherapy given for 2 to 3 years. Since myelosuppression and generalized immunosuppression are anticipated consequences of both leukemia and chemotherapy treatment, patients must be closely monitored at diagnosis and during treatment. Adequate facilities must be immediately available both for hematologic support and for the treatment of infections and other complications throughout all phases of therapy. Approximately 1% to 3% of patients die during induction therapy and another 1% to 3% die during the initial remission from treatment-related complications.[1,2] Children with ALL should be cared for at a center with specialized expertise in pediatric cancer.[3]

Nationwide clinical trials are generally available for children with ALL, with specific protocols designed for children at standard (low) risk of treatment failure and for children at higher risk of treatment failure. Clinical trials for children with ALL are generally designed to compare therapy that is currently accepted as standard for a particular risk group with a potentially better treatment approach that may improve survival outcome and/or diminish toxicities associated with the standard treatment regimen. Many of the therapeutic innovations that produced increased survival rates in children with ALL have been established through nationwide clinical trials, and it is appropriate for children and adolescents with ALL to be offered participation in a clinical trial. Treatment planning by a multidisciplinary team of pediatric cancer specialists with experience and expertise in treating leukemias of childhood is required to determine and implement optimum treatment.

Treatment for children with ALL is typically divided as follows:

• Remission induction (at the time of diagnosis).
• Postinduction therapy (after achieving complete remission).
  • Consolidation/intensification therapy.
  • Maintenance or continuation therapy.

Risk-Based Treatment Assignment

Risk-based treatment assignment is an important therapeutic strategy utilized for children with ALL. This approach allows children who historically have a very good outcome to be treated with modest therapy and to be spared more intensive and toxic treatment, while allowing children with a historically lower probability of long-term survival to receive more intensive therapy that may increase their chance of cure. As discussed in the Cellular Classification and Prognostic Variables section of this summary, a number of clinical and laboratory features have demonstrated prognostic value. The intensity of induction (some, but not all groups) is determined by National Cancer Institute (NCI) risk group and immunophenotype and postinduction therapy (all groups) is determined by prognostic factors such as early response determinations and cytogenetics.[4] With this treatment approach, approximately 80% of patients aged 1 to 18 years with newly diagnosed ALL treated on current regimens are expected to be long-term event-free survivors.[5,6,7,8,9,10]

In COG protocols, a subset of the known prognostic factors (e.g., age, white blood cell [WBC] count at diagnosis, immunophenotype, and presence of extramedullary disease) are used for the initial stratification of children with ALL into treatment groups with varying degrees of risk of treatment failure. Event-free survival (EFS) rates exceed 85% in children meeting good-risk criteria (aged 1-9 years, WBC count <50,000/?L, and precursor B-cell immunophenotype); in children meeting high-risk criteria, EFS rates are approximately 70%.[5,6,7,8,11] Additional factors, including cytogenetic abnormalities and measures of early response to therapy (e.g., day 7 and/or day 14 marrow blast percentage and minimal residual disease [MRD] levels at the end of induction), considered in conjunction with presenting age, WBC count, and immunophenotype, can identify patient groups with expected EFS rates ranging from less than 40% to greater than 95%.[11,12]