CHEMOTHERAPY INCREASES AML RISK 

Chemotherapy has increased survival rates and outcomes for a number of cancers, but the downside is that there can be a risk for treatment-related leukemia.

A study of acute myeloid leukemia (AML) from 1975 to 2008 indicates that the incidence is almost 5 times higher in patients treated with chemotherapy than in the general population (P < .001).

The analysis, published online February 14 in Blood, was led by Lindsay Morton, PhD, from the National Cancer Institute in Bethesda, Maryland.

The researchers warn that the overall incidence of treatment-related AML (tAML) is likely to increase in the future, because increasing numbers of patients have received cytotoxic agents during the past decade.

"Weighing the risks and benefits of treatment requires data from multiple sources, such as clinical trials demonstrating the benefits of treatment and studies that measure the risk of tAML and other short- and long-term side effects," Dr. Morton told Medscape Medical News.

"More research is needed to establish the risks of specific drugs at particular doses, and our study helps identify the most important groups of patients to include in such studies," she explained. More research is also needed "to clarify the role of a patient's genetic susceptibility to treatment-related leukemia."

Investigating the Risk

Dr. Morton and colleagues point out that the risk for tAML has long been recognized as a rare but highly lethal complication of treatment with cytotoxic chemotherapy. Although radiation therapy has also been implicated in tAML, the risk appears to be substantially higher with chemotherapy.

Even though cancer therapy has evolved dramatically over the past few decades, there has not been a large-scale study quantifying the risk for tAML after chemotherapy in adults with different types of cancers since 1984. In the current treatment era, data on tAML risk are scant, although case reports and small studies suggest that these risks have increased in conjunction with the expanded use of chemotherapy.

To investigate changes in tAML risk over time, the researchers used data from population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Program to identify patients at highest risk for tAML by time period, age at cancer diagnosis, latency, and the type of first primary tumor.

The patients were followed from the date of diagnosis until a second primary malignancy occurred, they reached the age of 85 years, they died, they were lost to follow-up, or the study period ended (December 31, 2008).

The researchers identified 426,068 adults who were diagnosed with a first primary malignancy from 1975 to 2008 and who received chemotherapy.

In this cohort, there were 801 cases of tAML; in the general population, the expected rate of AML would be 170.5 cases. This is a 4.7-fold increased risk, and an excess of 3.04 cases per 10,000 person-years.

In particular, the risk for tAML was especially pronounced in patients treated for Hodgkin's lymphoma, myeloma, and cancers of the bones/joints, soft tissue, ovary, and lung.

Almost half of all cases of tAML occurred after breast cancer or non-Hodgkin's lymphoma. The risk for tAML was also significantly higher after chemotherapy for cancers of the esophagus, anus, biliary tract, cervix, endometrium, testes, brain, and prostate, although this was based on fewer than 10 cases.

Even though more than 25% of patients with cancer of the stomach, colon, or rectum are treated with chemotherapy, tAML risks were not significantly elevated in this population.

Changes in Risk

For lung, breast, and endometrial cancer, the risk for tAML is very high in the first 5 years after initial diagnosis, but it drops substantially after that. For nonhematologic malignancies, there was no evidence of an elevated risk 10 years or more after diagnosis. For Hodgkin's lymphoma, non-Hodgkin's lymphoma, and myeloma, the 3- to 6-fold elevated risk for tAML persisted for 10 years or more.

There were striking changes in tAML risk by time period, with an increase in more recent years for non-Hodgkin's lymphoma and a decrease for ovarian cancer, myeloma, and possibly lung cancer.

For breast cancer, tAML risk was highest from 1975 to 1978, fell significantly in the 1980s, and then rose again, although nonsignificantly, during the 1990s.

For Hodgkin's lymphoma, the risk for tAML also varied substantially over time. Risk was high from 1975 to 1990, lower from 1991 to 1998, and increased (nonsignificantly) from 1999 to 2008.

The risk for tAML was higher with radiotherapy plus chemotherapy than with chemotherapy alone, although nonsignificantly, for cancers of the lung, breast, and ovary, but not for Hodgkin's lymphoma, non-Hodgkin's lymphoma, or myeloma. Changes in tAML risk by calendar period were unrelated to the therapy received.

This study was supported by the intramural program of the National Cancer Institute. The authors have disclosed no relevant financial relationships.

Blood. Published online February 14, 2013. Abstract