Patients treated with chemotherapy for a solid tumor are at much higher risk than was previously thought of developing a highly lethal blood cancer as a result of that treatment.

A research team from the National Cancer Institute (NCI) says that the relative risk of this late effect therapy-related myelodysplastic syndrome or acute myeloid leukemia (tMDS/AML) is exponentially higher than was supposed.

The new findings come from an analysis of longitudinal US cancer registry and treatment data for 700,612 patients who received chemotherapy between 2000 and 2013.

In that timeframe, the use of known leukemogenic agents, particularly platinum compounds, in initial chemotherapy has increased exponentially, from 10% in 2000-2001 to 81% in 2012-2013, they note.

"We have known for a long time that the development of myeloid leukemia is a very rare adverse effect of some types of cancer treatments that damage cells," Lindsay Morton, PhD, lead author of the study and a senior investigator in the NCI's Division of Cancer Epidemiology and Genetics, commented in a statement.

"There have been many changes in cancer treatment over time, including the introduction of new chemotherapy drugs and drug combinations, but we did not know what the risk of therapy-related leukemia looked like for patients since these changes were made," said Morton.

The study found that, by 2014, tMDS/AML had developed in 1619 patients (0.23% of 700,612 patients) who had been treated with chemotherapy for a first primary solid tumor.

Although the cumulative incidence of tMDS/AML was less than 1% for most solid tumor types, the prognosis was poor, the authors note: median overall survival was only 7 months and 78% (1270/1619) of the patients died. The report was published online December 20 in JAMA Oncology.

Risk Elevated in Many Tumor Types

The analysis showed that the relative risk of tMDS/AML was increased from 1.5-fold to more than 10-fold depending on the type of cancer treated and chemotherapy or chemoradiotherapy used. The risk was observed in 22 of 23 solid cancer types, with the exception of colon cancer.

The relative risks for tMDS/AML were highest (>10) in patients receiving chemotherapy for cancers of the bone, soft tissue, and testes (standardized incidence ratio [SIR], 39.0, 10.4, and 12.3, respectively). These cancers were typically diagnosed in younger patients, the analysis showed.

For patients who received chemotherapy for cancers of the peritoneum, small cell lung, ovary, fallopian tube, and brain or central nervous system, the SIRs were elevated 5- to 9-fold. For all remaining cancers, with the exception of colon cancer, the SIRs were elevated 1.5- to 4-fold.