Acute Lymphoblastic Leukemia, or ALL, is a cancer of the blood and bone marrow characterized by the overproduction of immature lymphocytes. Treatment is an intensive and prolonged process involving a combination of medications. While protocols provide a standardized framework, each plan is adapted to the individual patient, balancing aggressive therapy with safety. This multi-faceted approach is administered over several years.
The Phases of Treatment
Treatment for ALL is structured into distinct phases spanning two to three years, each with a specific goal. The initial and most intense phase is induction, which lasts about one month. The primary objective is to achieve a complete remission, where leukemia cells are no longer detectable in the bone marrow and blood counts are restored. This is accomplished with a combination of chemotherapy drugs, including vincristine, a corticosteroid like dexamethasone, and an asparaginase product.
Following successful induction, the consolidation phase begins. This stage is designed to eliminate any residual leukemia cells that survived the initial treatment to prevent relapse. Lasting for several months, this phase involves cycles of intensive chemotherapy. The drugs used can include some agents from induction as well as others like cyclophosphamide and cytarabine.
The final and longest phase is maintenance therapy, which lasts for approximately two years. This phase is the least intensive and aims to keep the leukemia in remission by using less aggressive treatments. Treatment involves daily oral chemotherapy, such as mercaptopurine and weekly methotrexate, supplemented with periodic intravenous drugs and steroids.
Central Nervous System Directed Therapy
A challenge in treating ALL is that many intravenous chemotherapy drugs do not pass the blood-brain barrier. This protective network of blood vessels can allow the central nervous system (CNS) to become a sanctuary for leukemia cells, leading to relapse. To prevent this, specific therapies are directed at the CNS throughout treatment.
The most common method is intrathecal chemotherapy. This procedure uses a lumbar puncture to inject drugs directly into the cerebrospinal fluid surrounding the brain and spinal cord. Methotrexate is a primary drug administered this way, sometimes with cytarabine and a steroid. These injections are performed at regular intervals during all treatment phases.
For patients at higher risk for CNS relapse, other strategies are used. High-dose systemic chemotherapy with drugs that better penetrate the blood-brain barrier, like intravenous methotrexate, is one approach. In some high-risk situations, cranial radiation may be used to treat the brain, though this is less frequent due to long-term side effects.
Medications and Administration
The treatment of ALL uses a variety of medications delivered through several routes. The specific combination and scheduling of these drugs are determined by the treatment protocol and phase.
Intravenous (IV) Chemotherapy
A significant portion of chemotherapy for ALL is administered intravenously, allowing drugs to circulate quickly through the bloodstream. This is done through a central venous catheter or port, which is surgically placed for long-term access. IV medications include vincristine, an anthracycline like daunorubicin, and cyclophosphamide. These drugs are given in a hospital or outpatient clinic during the more intensive phases of treatment.
Oral Medications
Oral medications are common in ALL treatment, particularly during the maintenance phase, as they can be taken at home. The most prominent oral chemotherapies are 6-mercaptopurine (6-MP), taken daily, and methotrexate, taken weekly. Corticosteroids, such as prednisone or dexamethasone, are also given as pills and are important in all treatment phases to destroy leukemia cells.
Intramuscular (IM) Injections
Some medications are injected directly into a large muscle, a method known as intramuscular injection. The primary drug administered this way is asparaginase or its longer-acting form, pegaspargase. This enzyme breaks down asparagine, an amino acid that leukemia cells need to survive. These injections are a component of the induction and consolidation phases.
Determining Individual Doses
The amount of each chemotherapy drug is calculated for each patient to maximize effectiveness while minimizing toxic side effects. This personalization is based on several factors that influence how the body processes the medications.
A primary method for calculating doses is based on Body Surface Area (BSA), a measurement derived from a person’s height and weight. BSA is a more accurate predictor of metabolic rate than body weight alone, allowing clinicians to scale a dose to the patient’s size. For certain drugs like vincristine, the total dose is capped to prevent nerve damage, regardless of BSA.
Personalization also comes from risk stratification. Patients are categorized into risk groups based on factors like age, initial white blood cell count, and specific genetic changes in the leukemia cells. Patients in higher-risk groups receive more intensive protocols, which may involve higher doses or additional drugs.
Pharmacogenomics allows for dosing adjustments based on a patient’s genetics. For instance, testing for the thiopurine S-methyltransferase (TPMT) enzyme is done before starting mercaptopurine (6-MP). Individuals with low TPMT activity break down the drug more slowly, so doctors adjust the dose to a safer level to prevent side effects.
Doses of various drugs may also be temporarily reduced or delayed if a patient experiences significant side effects, such as very low blood counts or issues with kidney or liver function.
Advanced and Salvage Therapies
For patients with refractory or relapsed ALL, or those with very high-risk disease, advanced treatments beyond standard chemotherapy are available. These therapies offer alternative ways to target and destroy leukemia cells.
Targeted therapy uses drugs that attack specific vulnerabilities in cancer cells. For example, Tyrosine Kinase Inhibitors (TKIs) are used for patients with Philadelphia chromosome-positive (Ph+) ALL. This genetic abnormality creates a protein that drives cancer growth, and TKIs like imatinib block this protein’s action.
Immunotherapy uses the body’s immune system to fight cancer. One approach is blinatumomab, an antibody that connects a patient’s T-cells to leukemia cells, enabling the T-cells to attack the cancer. Another immunotherapy is CAR-T cell therapy, where a patient’s T-cells are genetically engineered to recognize and destroy leukemia cells.
For some patients with relapsed or very high-risk ALL, an allogeneic stem cell transplant is an option. This procedure involves high-dose chemotherapy to eliminate the leukemia and bone marrow. The patient then receives an infusion of healthy blood-forming stem cells from a donor to rebuild a new blood and immune system. This is reserved for specific situations due to potential complications.