Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, affecting blood and bone marrow. Historically challenging, treatment advancements have led to survival rates exceeding 90%, offering substantial hope. This article clarifies the comprehensive treatment strategy for pediatric ALL, from diagnosis through long-term survivorship.
Treatment Phases and Goals
Pediatric ALL treatment involves several distinct phases, often lasting two to three years, with initial months being most intensive. This multi-stage approach aims to eliminate leukemia cells and prevent recurrence. The specific duration and intensity of each phase can vary based on the child’s risk group and the treatment protocol used.
The first phase, Induction, typically lasts four to six weeks, aiming to achieve remission. Leukemia cells are targeted to clear them from bone marrow, allowing normal blood cell production to resume. Over 95% of children with ALL achieve remission following this initial month of treatment.
After successful induction, the Consolidation (or Intensification) phase begins, usually lasting several months. This phase eradicates any remaining leukemia cells, preventing resistance. Different chemotherapy drugs are often combined during this period to maximize their effectiveness.
Some protocols include an Interim Maintenance phase, lasting around eight weeks, to further reduce residual leukemia cells. This is sometimes followed by a Delayed Intensification phase, a re-induction using more intensive chemotherapy before the final maintenance stage. The final and longest phase is Maintenance therapy, lasting approximately one and a half to two and a half years. This phase uses lower doses of chemotherapy to sustain remission, kill any undetectable leukemia cells, and prevent the disease from returning.
Specific Treatment Approaches
Chemotherapy is the primary treatment for pediatric ALL, using various drugs to destroy leukemia cells. Medications are administered through various routes, including intravenously, orally, and intrathecally into the cerebrospinal fluid to address leukemia cells in the brain and spinal cord. Common drugs include L-asparaginase, vincristine, methotrexate, 6-mercaptopurine, and corticosteroids like dexamethasone.
Targeted therapy represents a significant advancement, addressing specific genetic mutations in leukemia cells. For instance, children with Philadelphia chromosome-positive ALL often receive tyrosine kinase inhibitors (TKIs) like imatinib. These drugs work by blocking the activity of a protein called BCR-ABL1, which drives the growth of leukemia cells. Second-generation TKIs such as dasatinib and nilotinib are also used, particularly in cases of imatinib resistance, with dasatinib notably able to cross the blood-brain barrier.
Immunotherapy, specifically CAR T-cell therapy, offers a novel approach for relapsed or refractory B-cell ALL. In this therapy, a patient’s own T-cells are collected and genetically modified to express chimeric antigen receptors (CARs) that recognize CD19 on leukemia cells. These re-engineered T-cells are then infused back into the patient, where they destroy CD19-expressing cancerous B-cells.
Central Nervous System (CNS) prophylaxis prevents leukemia cells from spreading or relapsing in the brain and spinal cord. This is typically achieved through intrathecal chemotherapy, injecting drugs like methotrexate directly into the cerebrospinal fluid via a lumbar puncture. In some higher-risk cases, cranial radiation therapy may also be used with intrathecal chemotherapy, though its use is limited due to potential long-term side effects.
For high-risk or relapsed patients, hematopoietic stem cell transplantation (HSCT) can be a curative option. This procedure replaces diseased bone marrow with healthy stem cells, often from a donor. While HSCT carries risks, advancements in donor matching and supportive care have improved outcomes for challenging cases.
Managing Treatment’s Impact
Pediatric ALL treatment, though effective, can cause short-term impacts due to its effect on rapidly dividing cells. Nausea and vomiting are common; antiemetic medications help manage these symptoms. Hair loss is another frequent side effect, often temporary with regrowth occurring within months after treatment.
Fatigue
Fatigue is common, with children often feeling tired during and after treatment due to anemia and the body’s response to therapy. Blood transfusions can help address anemia; rest and light physical activity aid in managing energy levels.
Myelosuppression and Infection Risk
Myelosuppression, a reduction in bone marrow activity, leads to low blood cell counts and increased infection risk due to decreased white blood cells (neutropenia). Antibiotics prevent or treat infections, and meticulous hygiene minimizes pathogen exposure.
Other common effects include:
- Mucositis, which causes painful sores in the mouth and throat, managed with pain medication and good oral hygiene.
- Peripheral neuropathy, characterized by numbness, tingling, or weakness, can result from nerve damage caused by some chemotherapy drugs.
- Nutritional support, as appetite changes can occur.
- Pain management for various discomforts.
Life After Active Treatment
After active pediatric ALL treatment, long-term follow-up care is an ongoing part of a survivor’s health journey. This involves regular check-ups, blood tests, and screenings to monitor for disease recurrence. The frequency and type of monitoring are tailored based on the specific treatments received and the child’s individual risk factors.
Survivors face an increased risk of developing late effects years after treatment. These can affect various organ systems. Examples include mild cognitive changes, cardiac effects from certain chemotherapy drugs, or an increased risk of secondary cancers in adulthood.
Healthcare providers use comprehensive guidelines, such as those by the Children’s Oncology Group (COG), to standardize screening and management of potential long-term issues. Beyond medical monitoring, a healthy lifestyle, including balanced nutrition and regular physical activity, promotes overall well-being. Psychosocial support for survivors and their families is also important, addressing emotional and social adjustments after treatment.