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Researchers are now studying the causes, diagnosis, and treatment of childhood leukemia at many medical centers, university hospitals, and other institutions.

Genetics

Scientists are making progress in understanding the changes in the DNA inside bone marrow stem cells that can cause them to develop into leukemia cells. Understanding these gene and chromosome changes can help explain why these cells may grow out of control, and why they don’t develop into normal, mature blood cells. Doctors are now looking to use these changes to help them determine a child’s outlook and to determine what treatment is likely to be best.

This progress has already led to vastly improved and very sensitive tests for detecting leukemia cells in blood or bone marrow samples. The polymerase chain reaction (PCR) test, for example, can identify very small numbers of leukemia cells based on their chromosome changes. This test is useful in determining how completely the leukemia has been destroyed by treatment, and whether a relapse is likely if further treatment isn't given. Newer tests known as next generation sequencing (NGS) tests, which are just now coming into use, might be able to help with this even more.

Causes, and possibly prevention

Researchers continue to look for possible causes of leukemia in children, which might include a combination of both genetics and environmental exposures. 

For example, one theory that has gained some ground in recent years is that some childhood leukemias might be caused by a combination of certain gene changes that happen very early in life (even before birth), along with being exposed to certain germs (particularly viruses) later than normal. This “delayed infection” (after the first year or so of life) might affect the immune system in a way that leads to a second gene change, which in turn might lead to leukemia.

This might help explain why some studies have found that the risk of childhood leukemia seems to be lower in children who were in daycare during their first year of life (which would have exposed them to common infections earlier).

More research is needed to confirm this theory. But if it is confirmed, it might be possible to lower childhood leukemia risk by ensuring children are exposed to certain germs very early in life.  

Clinical trials

Most children with leukemia are treated at major medical centers, where treatment is often given in clinical trials to help ensure children get the most up-to-date care. Several important questions are now being studied in clinical trials. Among them are:

• Why do some children with acute lymphocytic leukemia (ALL) relapse after treatment, and how can this be prevented?
• Are there other prognostic factors that will help identify which children need more or less intensive treatment?
• Can chemotherapy drug resistance in acute myelogenous leukemia (AML) be reversed?
• Are there better drugs or combinations of drugs for treating the different types of childhood leukemia?
• When should a stem cell transplant be used to treat leukemia?
• How effective are stem cell transplants in children who don’t have a brother or sister who is a good tissue type match?
• Can a second stem cell transplant help children who relapse after a first stem cell transplant?
• What are the best treatment approaches for children with less common forms of leukemia, such as juvenile myelomonocytic leukemia (JMML) and chronic myeloid leukemia (CML)?

Immunotherapy to treat childhood leukemia

Immunotherapies are treatments that boost a child’s own immune system to help fight leukemia. Some types of immunotherapy have shown a lot of promise in treating childhood leukemia, even when other treatments are no longer working.

Chimeric antigen receptor (CAR) T-cell therapy

In this treatment, immune cells called T cells are removed from the child’s blood and genetically altered in the lab to help them attack leukemia cells. The T cells are then given back into the child’s blood, where they can seek out the leukemia cells throughout the body.

This technique has shown very encouraging results in clinical trials against some advanced, hard-to-treat cases of ALL. In many children the leukemia could no longer be detected after treatment, although it’s not yet clear if these children have been cured.

Doctors are still improving how they make the T cells and are learning the best ways to use them. CAR T-cell therapy is only available at certain major medical centers at this time.

Monoclonal antibody therapy

Antibodies are proteins made by the body’s immune system to help fight infections. Man-made versions, called monoclonal antibodies, can be designed to attack a specific target, such as a protein on the surface of leukemia cells.

An example is blinatumomab (Blincyto), a special kind of monoclonal antibody that can attach to 2 different proteins at the same time. This drug brings the leukemia cells and immune cells together, which is thought to cause the immune system to attack the leukemia cells. This drug can be used to treat some types of B-cell ALL.

For more on these treatments, see Immunotherapy for Childhood Leukemia.

Other types of immunotherapy are now being studied as well.

New targeted drugs to treat AML

As researchers have learned more about the gene changes that drive the growth of leukemia cells, they’ve begun to develop drugs that can target these gene changes. For example, several newer types of targeted drugs are now being used to treat adults with AML, and many of these are now being tested for use in children as well.

FLT3 inhibitors: These drugs attack cells with a mutated FLT3 gene. Examples include midostaurin (Rydapt) and gilteritinib (Xospata).

IDH inhibitors: These drugs target leukemia cells that have mutations in the IDH1 or IDH2 gene. Examples include ivosidenib (Tibsovo) and enasidenib (Idhifa).

BCL-2 inhibitors: These drugs attack BCL-2, a protein that can help leukemia cells live longer. An example is venetoclax (Venclexta).