While the absolute risk of therapy-related blood cancers is low, the treatment is often intensive and linked to substantial morbidity.
After chemotherapy for most solid tumors, the risk for certain rare blood cancers, such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (tMDS/AML), may be elevated, according to recent findings. However, since most data about these rare blood cancers come from case studies or small case-controlled studies, the association is not well understood.
Investigators from the National Cancer Institute speculated whether there was an association of tMDS/AML with specific types of chemotherapy, including those currently used for solid cancer treatment. As a result, they conducted a population based study based on registrants in the Surveillannce, Epidemiology, End Results (SEER) study, and Medicare claims to quantify the tMDS/AML risk after chemotherapy in the years 2000 and onward in adults in the United States. Additionally, they wanted to corelate the tMDS/AML risks with chemotherapy treatment practices.
The analysis included 1,619 tMDS/AML cases from more than 700,000 adults aged 20 to 84 years diagnosed with first primary solid cancer between 2000 and 2013. Investigators then examined the data from 165,820 older adults (aged 66 to 84 years).
“In the modern treatment era, the population of patients treated with chemotherapy who are at risk for developing tMDS/AML is substantially expanded compared with patients treated in the past,” study author Lindsay Morton, PhD told MD Magazine. “This expansion coincides with an increase in the use of platinum-based chemotherapy, which can be highly effective for treating many types of cancer, but it has also been associated with increased tMDS/AML risk.”
The overall survival following a diagnosis with tMDS/AML was poor. A majority of the patients (80%) died in the median survival of 7 months.
The investigators also learned that among patients currently being treated with chemotherapy, about three-quarters of the tMDS/AML cases diagnosed in the next 5 years are likely to be linked to chemotherapy.
From the data, Morton and her team found that the use of known leukemogenic agents in initial chemotherapy, such as platinum compounds, increased substantially since 2000. The team noted these most often occurred as gastrointestinal tract cancers, including esophagus, stomach, colon, and rectum cancers with the risk present in 22 of 23 solid cancer types. They tallied just 10% between 2000 and 2001 but spiked to 81% in 2012 and 2013.
“These findings suggest a substantial expansion in the patients at risk for tMDS/AML because in the past, excess risks were established only after chemotherapy for cancers of the lung, ovary, breast, soft tissue, testis, and brain or central nervous system,” the study authors wrote.
Compared with a study conducted in a similar manner, with patients first diagnosed with cancer between 1975 and 2008, these results appeared to show double the number of solid cancer patients treated with chemotherapy and more than triple the amount of tAML cases and tMDS.
“Physicians and patients should be aware of the risk of therapy-related leukemia,” Morton added. “This research emphasizes the importance of continued efforts to minimize exposure to cytotoxic chemotherapy without sacrificing efficacy. The development of new effective agents and cancer treatment approaches with fewer late sequelae (aftereffects) is also critical.”
The team estimated that about 360,000 adults who have survived a year or more after a solid cancer diagnosis in 2018 will have received initial chemotherapy. By 2023, they estimate 714 tMDS/AML cases could be attributed to chemotherapy.
Consequently, the team noted that treatment risks and benefits should be carefully assessed, and that the development of less toxic chemotherapeutic approaches are needed.
The paper, titled “Association of Chemotherapy for Solid Tumors With Development of Therapy-Related Myelodysplastic Syndrome or Acute Myeloid Leukemia in the Modern Era,” was published in the Journal of the American Medical Association (JAMA) Oncology.