Rising Risk of Secondary Blood Cancers After Chemo and Radiation

A population-based study in Japan has indicated a gradual increase in the rates of secondary blood-related cancers that develop following chemotherapy or radiation treatments. These secondary malignancies, which occur after a patient has been treated for an initial primary cancer, represent a significant challenge in long-term survivorship care.

Secondary malignancies are entirely new cancers that emerge following the treatment of a primary cancer. In the United States, these account for 19% of all cancer diagnoses, and cancer survivors have a 14% higher rate of new cancer diagnoses compared to the general population.

Risk Factors in Radiation and Chemotherapy

Radiation therapy has been linked to an increased risk of both liquid and solid secondary cancers. For secondary leukemias and myelodysplastic syndromes, the level of risk is influenced by the radiation dose, the amount of bone marrow exposed, and the radiation dose rate, which includes the frequency of treatment and the amount administered per treatment over a specific time frame.

Secondary solid malignancies typically develop several years after radiation therapy is completed. The risk for these cancers is affected by the area radiated, the dose, and the age of the patient during the time they received the treatment.

Chemotherapy is also linked to the development of myelodysplastic syndromes and leukemias. Specific classes of chemotherapy reported to increase the risk for secondary malignancies include:

• Alkylating agents
• Platinum-based chemotherapy
• Anthracycline topoisomerase II inhibitors

targeted therapies such as BRAF inhibitors, including dabrafenib and vemurafenib, may increase the risk of developing squamous cell cancers of the skin.

The Role of Clonal Hematopoiesis

Research from Memorial Sloan Kettering Cancer Center has explored why some patients develop secondary blood cancers, such as therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), while others do not. These specific therapy-related blood cancers are described as aggressive and often do not respond well to treatment.

The research focuses on clonal hematopoiesis (CH), a process where a hematopoietic stem cell develops a spontaneous mutation and begins producing more cells with that same genetic mutation. It’s estimated that 10 to 20 percent of people over age 70 have these spontaneous mutations in their blood.

A study involving 24,000 people at Memorial Sloan Kettering found CH in approximately one-third of the participants. The investigators observed that rates of CH were increased in individuals who had already received treatment, specifically certain chemotherapies—such as topoisomerase II inhibitors or platinum drugs—and radiation therapy.

Broader Risk Factors and Incidence

Beyond medical treatments, other factors may contribute to the risk of secondary cancers. A 2024 Danish study by Kjaer et al. Found significant retrospective connections between the development of secondary cancers and viruses, red meat, tobacco, and alcohol.

The Danish study also noted that the highest cumulative incidence of secondary cancer occurred during the 10 years following the initial cancer, particularly in patients who had primary cancers of the bladder/genitourinary system, the oropharyngeal area, or the larynx.

While some evidence suggests radiation therapy is linked to subsequent cancers, other sources note that radiation therapy alone does not appear to increase the risk of secondary leukemia.