Causes, Risk Factors, and Prevention of Childhood Leukemia

Children with Down syndrome have an extra (third) copy of chromosome 21. They are more likely to develop either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) than other children, with an overall risk of about 2% to 3%. Down syndrome has also been linked with transient leukemia (also known as transient myeloproliferative disorder [TMD or TAM]), a leukemia-like condition within the first month of life, which may resolve on its own with no or very little treatment.

Li-Fraumeni syndrome is a rare condition caused by a change in the TP53 gene. People with this change have a higher risk of developing several kinds of cancer, including leukemia, bone or soft tissue sarcomas, breast cancer, adrenal gland cancer, and brain tumors.

NF1 is a cancer syndrome caused by a change in the NF1 gene that causes tumors to grow on the skin, nerves, and bones. It increases the risk of developing several types of cancer, including leukemias.

When the bone marrow fails, the bone marrow is unable to make enough healthy blood cells and blood counts are low. The failing bone marrow can create cells with DNA that is fragile, has mutations, or is unprotected, leading to damage. This increases the risk of many types of cancer. Some examples of these bone marrow failure syndromes are Fanconi Anemia (FA), Dyskeratosis congenita (DKC), and Shwachman-Diamond Syndrome (SDS).

In these conditions, the immune system does not work properly. This can lead to infections and the growth and division of damaged cells, causing cancers like leukemia. These conditions include Ataxia-telangiectasia (AT) and Bloom syndrome.

Noonan syndrome is a genetic condition that has been associated with JMML.

Exposure to high levels of radiation is a risk factor for childhood acute leukemias. It is also the only known environmental risk factor for CML. Japanese atomic bomb survivors had a high risk of developing leukemias. If a baby is exposed to radiation before birth, there may also be an increased risk of childhood leukemia, but the extent of the risk is not clear.

The possible risks from fetal or childhood exposure to lower levels of radiation, like radiation from x-rays or CT scans, are not known. Some studies have found a slight increase in risk, while others have found no increased risk. Any risk increase is likely to be small. However, to be safe, most doctors recommend that pregnant women and children do not get these tests unless they are needed.

Children and adults treated for other cancers with certain chemotherapy drugs have a higher risk of getting a second cancer, such as AML, later in life. Drugs like cyclophosphamide, doxorubicin, etoposide, and teniposide have been linked to a higher risk of leukemia. These leukemias usually develop within 10 years of treatment, and they tend to be harder to treat.

Exposure to chemicals such as benzene (a solvent used in the cleaning industry and to manufacture some drugs, plastics, and dyes) may cause acute leukemia in adults and, rarely, in children. Exposure to perfluoroalkyl substances (PFAS) found in common household items like non-stick cookware and exposure to higher amounts of air pollution in early life have also been associated with childhood leukemias.

Several studies have found a possible link between childhood leukemia, specifically AML, and household exposure to pesticides either before birth or in early childhood. Some studies have also found parental exposure to paint and solvents to be associated with a higher risk of pediatric AML.

Studies of environmental exposures can be difficult to do. More research is needed to confirm these findings and provide more specific information about the possible risks.

Viral infections have been linked to some types of childhood cancers.

The immune system plays a crucial role in fighting infections and removing injured or damaged cells. In some cases, researchers think that some childhood leukemias may result from an abnormal immune system response to an infection.

One theory suggests that childhood leukemia may develop more commonly in children exposed to certain germs (particularly viruses) later than normal. This “delayed infection” (after the first year of life) might affect the immune system in a way that allows abnormal cells to escape the system. 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.

Other researchers suggest that the movement of people around the world is resulting in exposure to new germs. Research suggests this may trigger an abnormal immune response which leads to leukemia development.

Children who are getting intensive treatment to suppress their immune system (mainly children who have had organ transplants) have an increased risk of certain cancers, such as lymphoma and ALL.

Doctors are looking for ways to treat people without raising the risk of leukemia. For now, the benefits of treating life-threatening diseases with organ transplants must be balanced against the small chance of developing leukemia several years later.