Treatment of Pediatric Acute Lymphoblastic Leukemia

Key points

Risk stratification of newly diagnosed acute lymphoblastic leukemia

One of the hallmarks of the treatment of childhood ALL is the reliance on risk-based stratification. By identifying the features that have been shown to affect prognosis, patients can be classified into groups based on risk of treatment failure. Those with favorable features can be treated with less toxic regimens, whereas more aggressive regimens are reserved for those with more high-risk disease.

It is therefore paramount to identify those features shown to consistently affect prognosis and,

Treatment of newly diagnosed acute lymphoblastic leukemia

There are 4 major components of treatment of newly diagnosed ALL, reflecting a reliance on multidrug regimens to avoid development of resistance. Different blocks of chemotherapy have varying intensity depending on the group of patients at risk, with increasingly intensive regimens corresponding to more aggressive disease categories.

Remission induction is the first block of chemotherapy, lasting 4 to 6 weeks. Patients are usually admitted to the hospital for their initial treatment and workup,

Considerations for particular subgroups of acute lymphoblastic leukemia

Infants with ALL represent a particularly high-risk subclass, with higher risks of both treatment failure and treatment complications. The highest rates of treatment failure are seen in infants diagnosed before 6 months of age, those with high initial WBC count, or those with MLL gene rearrangements (which occur in 70%–80% of infants diagnosed with ALL). Infant regimens often contain intensive chemotherapy not typically administered on other ALL protocols. In cases with MLL rearrangement, the

Treatment of relapsed acute lymphoblastic leukemia

Despite significant advances in treatment, approximately 15% to 20% of patients with ALL will suffer relapsed disease, the most common cause of treatment failure. With intensive therapy that may include HSCT, overall survival from relapsed ALL is approximately 40%.³⁷ Similar to those patients with newly diagnosed ALL, those with relapsed disease can be risk stratified. Length of first complete remission (CR1) and site of relapse have consistently been demonstrated to be the 2 most important

Novel agents in the treatment of acute lymphoblastic leukemia

Current efforts in advancing the treatment of ALL focus on unique mechanisms that contrast with the nonspecific targeting of conventional chemotherapy. Immunotherapy is a broad and promising field that seeks to harness the power of the immune system to allow for a more targeted approach. Chimeric antigen receptors are one example of modified adoptive cell transfer whereby the patient’s own cytotoxic T cells are genetically engineered to express an antibody to target leukemic antigens (often

Toxicities in the treatment of acute lymphoblastic leukemia

Almost all chemotherapy agents cause myelosuppression, mucositis, and nausea/vomiting. Unique effects of common chemotherapeutic agents used in the treatment of ALL are listed in Box 2.

Summary

Acute lymphoblastic leukemia is treated with a combination of chemotherapy drugs over the course of several years, with an overall survival of approximately 80% for all newly diagnosed patients. Those patients with higher risk of relapse receive more aggressive treatment, whereas those with more favorable features can be spared the more toxic effects. Treatment is progressively less intensive as the duration of therapy progresses, and must include central nervous system (CNS) directed therapy