Persons who have undergone cytotoxic chemotherapy for certain cancers, notably non-Hodgkin lymphoma, may be at risk for developing acute myeloid leukemia (AML). Although therapy-related AML (tAML) was known to be rare, a new study indicates that the risk of this highly fatal complication has risen over the past three decades for some types of cancer while declining for others.

As explained in the journal Blood by Lindsay M. Morton, PhD, of the National Cancer Institute (NCI) in Bethesda, Maryland, and colleagues, data describing tAML risks over time are sparse despite major changes in cancer treatment over the years.

“It has long been known that some types of chemotherapy are associated with a high risk of developing subsequent leukemia, particularly when treatments include certain alkylating agents,” clarified Morton in an NCI statement. “The goal of this study was to better understand how cancer patients’ risk of developing leukemia has changed over time.”

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Morton’s group evaluated information from 426,068 U.S. adults who were initially administered chemotherapy for first primary malignancy between 1975 and 2008. The investigators identified a total of 801 cases of tAML—4.7 times more than expected in the general population.

The data revealed that over the time period studied, tAML risks increased following therapy for non-Hodgkin lymphoma. The evidence also pointed to an increase in risk since 2000 among patients receiving treatment for esophageal, prostate, or cervical cancer, and since the 1990s among those receiving treatment for bone and joint cancers or endometrial cancer.

Alternatively, tAML risk declined in relation to treatment for ovarian cancer and myeloma, and possibly for lung cancer. Although information on the specific chemotherapy drugs used was not available, the reduced risk for tAML following ovarian cancer therapy was consistent with a shift from the use of the alkylating agent melphalan to platinum-based chemotherapy for that disease in the early 1980s.

Risk of tAML varied significantly by patient age at first cancer and latency. Radiotherapy for lung, breast, and ovarian cancers nonsignificantly increased tAML risk.

The authors noted that the risk of developing tAML is generally low for an individual patient, and the increased risk among survivors of non-Hodgkin lymphoma could be due to prolonged survival in recent years for some lymphoma subtypes that are associated with multiple courses of chemotherapy.

Future studies are needed to ascertain tAML risk associated with specific chemotherapy agents, and to identify patient groups at greatest risk of tAML so that efforts can be made to prevent the disease, particularly in persons undergoing treatment for cancers with favorable survival potential.