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Leukemia makes up about 33% of all childhood cancers. The conventional way to treat ALL is through chemotherapy, which is conducted in three phases: induction, consolidation and maintenance, and leads to a survival rate of 85%.

Leukemia is the most common cancer in children and teenagers and makes up about 33% of all childhood cancers. Most pediatric leukemia cases are a specific type called Acute Lymphocytic Leukemia (ALL). Typical symptoms of leukemia in children are swelling of organs, swollen lymph nodes, enlargement of thymus, infections, and fever, and other symptoms, particularly in children with leukemia have advanced enough to have cancer spread to the brain and spinal cord before diagnosis.  

The conventional way to treat ALL is through chemotherapy, which is conducted in three phases:

  • induction,
  • consolidation and
  • maintenance.

By the time a definite diagnosis of leukemia has been made, there are generally already 100 billion leukemia cells in the body. In order to achieve remission, the initial phase of the treatment is to destroy 99.9% of all leukemia cells [1].

The goal of the first phase of the chemotherapy regimen, induction, is to destroy 99.9% of all leukemia cells within 1 month, but that still leaves behind 100 million leukemia cells present in the body that also need to be killed. Therefore, the next phase, also called the consolidation phase, is instituted, which is a one to two-month consolidation program that destroys the remaining leukemia cells. Then, two years of subsequent maintenance chemotherapy helps kill any residual cancer cells.

The types of chemotherapies used in this procedure are dependent on whether leukemia has been categorized as standard-risk, high-risk or very high-risk, as determined by doctors [2].

Phase 1 in treatment of Acute Lymphocytic Leukemia in Children: Induction

As mentioned above, the goal of induction in treatment is to achieve remission by killing 99.9% of all leukemia cells. The end goal of this phase is to have no leukemia cells found in the bone marrow samples of patients. Ideally, the patient will have normal marrow samples and normal blood counts.[3]

Most children, approximately 95%, enter remission within 30 days of treatment. As this is the very intense cycle of chemotherapy, it requires long stays at the hospital and many visits with the doctor.

In fact, for one month, the child may spend most of their time in the hospital due to the fact that intense chemotherapy can severely affect the immune system and very serious infections can occur [4].

Therefore, it is very important for the children that are undergoing this stage of therapy to take all the medications correctly as complications related to this treatment can be fatal. Generally, children that are classified as being standard-risk will be administered three different drugs for the first month, which include the drugs:

  • L-asparaginase,
  • vincristine
  • and a steroid drug.

For children that have high-risk ALL, another drug in the anthracycline class is added. Some other drugs that may be administered include methotrexate and 6-mercaptopurine [5].

As part of the induction process, children are also given intrathecal chemotherapy, which means administering chemotherapy straight in the cerebrospinal fluid of patients through a small procedure called the spinal tap. This is conducted to kill any circulating leukemia cells that are present in the brain and the spinal cord. It is conducted two times in the first month and between four to six times in the next 1 or 2 months.

The drug that is usually given is called methotrexate but other drugs may be added for children at a higher risk of disease [6].

Phase 2 in treatment of Acute Lymphocytic Leukemia in Children: Consolidation

The next phase after induction is about one to two months and is called the consolidation phase. The goal of consolidation is to, once again, reduce the number of leukemia cells in the body. There are many chemotherapeutic drugs that are used to undergo this phase of treatment and the therapy itself uses a combination of these drugs as otherwise the leukemia cells tend to develop a resistance to therapies. During this time, intrathecal therapy continues.

For standard-risk leukemia, children are treated with the drugs methotrexate and 6-mercaptopurine. However, the combination of drugs differs based on the cancer center and the doctor. Other drugs such as vincristine, L-asparginase and prednisone may also be used.

Finally, for high-risk patients, even more drugs are added and used. For these patients, there may also be a second round of chemotherapy with the same drugs that work to completely eliminate all cancer cells [7]. In some cases, there are patients with a type of ALL called Philadelphia chromosome-positive ALL, which refers to a chromosome defect. These patients have a very good targeted treatment called imatinib [8].

Phase 3 in treatment of Acute Lymphocytic Leukemia in Children: Maintenance

Once remission has been achieved in the induction and it remains throughout consolidation, a therapy known as the maintenance therapy can start.

Treatment includes administering 6-mercaptopurine daily and methotrexate weekly. Vincristine and a steroid drug are also administered, however, these are only given for a small period of time every one to two months. Other drugs can also be added to the regimen depending on the risk level of the patient. 

Generally, for the first one to two months, most maintenance therapy plans are very intense, somewhat similar to induction, which is why they are often called re-induction. Children that are in the higher-risk category can have this period be even longer as doctors try to personalize treatment plans.

The total amount of therapy is generally between two to three years. Unfortunately, there is a high risk of recurrence, particularly in boys, which is why doctors often administer chemotherapy for longer in boys [9].

Conclusion

As the survival rate for ALL is almost 85%, this treatment regimen, which includes induction, consolidation and maintenance, works very well for children with Acute Lymphocytic Leukemia. This treatment works ideally if the leukemia is caught at a lower stage and therefore, it is important to stay diligent and monitor for signs of leukemia in children [10].

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