Decades after the Vietnam War, hematology-oncologist Michael Sekeres began seeing veterans in his clinic with myelodysplastic syndromes, a group of blood cancers known as MDS. Many of the veterans had been exposed to Agent Orange, a blend of herbicides used by the military to strip dense foliage during the war.
This exposure has long been associated with many serious diseases, including some cancers, but not with MDS. In data published this month in the journal Blood Advances, Sekeres and his colleagues were able to provide clear evidence that exposure to Agent Orange is associated with MDS and may cause an earlier, more aggressive form of the disease.
“I’ve described this as my passion project because I’ve been treating these people for years,” said Sekeres, chief of hematology at the University of Miami Sylvester Comprehensive Cancer Center. “Most of these young people were exposed in the ’60s and ’70s and then developed MDS in the 2010s and 2020s. I had several veterans who were exposed to Agent Orange.”
One of the herbicides in Agent Orange, made by companies such as Monsanto and Dow Chemical, became contaminated with extremely toxic compounds called dioxins during the manufacturing process. Dioxins have caused severe birth defects in the children of people exposed to the toxin, and can also significantly increase the risk of developing several different types of cancer.
American soldiers sprayed Agent Orange from the air and the ground into the jungles of Vietnam and neighboring countries, often mixing it with kerosene or fuel, another carcinogen, to aid in the dispersal. This revelation led the Department of Veterans Affairs to identify several cancers as being linked to Agent Orange, and veterans with these specific conditions were able to receive benefits from the agency.
The invisible battle: The harsh reality of veterans’ health care access
But it’s not MDS, Sekeres said. He hopes the study will provide affected veterans with a path to receiving benefits. STAT spoke to Sekeres about the effort. This interview has been edited for length and clarity.
What made you interested in this research?
I had several veterans who developed MDS from exposure to Agent Orange. Bad things happen to people as they age, so it was difficult to know if this was due to Agent Orange or unrelated. There is absolutely biological plausibility that this is a risk factor for ultimately developing MDS, and all that remained was to obtain a suitable registry to prove this.
In Vietnam, it was used as a defoliant. Veterans exposed. The Vietnamese people were exposed to it. Dioxins and fuels are thought to be associated with myeloid malignancies. We have long suspected that this could lead to MDS, but until now neither the military nor formal research had revealed the link.
Why was this important to you?
The Department of Veterans Affairs already recognizes that some cancers are putatively linked to Agent Orange. This allows veterans to receive certain benefits. However, the Veterans Administration has not yet confirmed that MDS is presumed to be related to Agent Orange. My hope and goal with this study is to help these older veterans finally receive the disability compensation they deserve.
At this time, unless the Department of Veterans Affairs recognizes this link, my patients must try to provide medical evidence of a direct link between their exposure and their illness, which is nearly impossible. It’s a terrible disease. As MDS worsens, blood cell count abnormalities also worsen. People become dependent on red blood cell transfusions, making them more susceptible to bleeding and infections that can lead to death.
How did you study?
We did that through MDS natural history research. This is a really cool study that we conducted over almost a decade. The goal is to study the natural history of MDS from the moment people are diagnosed with MDS at 160 facilities across the country, enrolling people from the moment MDS is suspected. This means they have some kind of blood abnormality and have been referred to a hematologist. About half had MDS or its precursor, while half did not have MDS.
We tried very carefully to make sure that people answered the questionnaire about whether they had been exposed to defoliants.
What were some of the study’s key findings?
Six percent of the people in the study had been exposed to defoliants. Of those exposed to Agent Orange, 54% were ultimately found to have MDS or prodromal symptoms, while 37% of those were not found to have MDS or prodromal symptoms. In our study, we found that it was also significantly associated with people who had more molecular mutations. Not only did they have MDS, but poor or very poor genetic risk groups had more complex MDS. We actually showed that people exposed to defoliants were more likely to develop MDS.
That makes sense. They were exposed in their late teens or early 20s. I call this the tough rose road to cancer. The first mutations occur at a young age. That way, you are more likely to get it at a younger age. By the time it is discovered, it is more likely to cause complications.
What is interesting is that the black race has appeared one after another. They were three times more likely to be infected than white people. Blacks who served in Vietnam were in more vulnerable positions, such as on the front lines, and were more likely to be exposed to defoliants.
Michael SekeresProvided by: Sylvester Comprehensive Cancer Center
Are the results generalizable beyond the study population? American soldiers weren’t the only ones exposed to these toxins. Civilians in Vietnam and neighboring countries were also affected by exposure to defoliants.
absolutely. Anyone who comes into contact with Agent Orange is potentially at risk for developing MDS. We were able to identify very different genetic mutations in MDS samples from people exposed to defoliants and those who were not. Building facts greatly increases the likelihood of establishing a causal relationship.
If I were a Vietnamese citizen exposed to the atomic bomb and my blood cell count started to rise abnormally, I would seek medical attention immediately to see if I could diagnose it early. Treatments are more effective and can help people enjoy a better quality of life.
You have been seeing these patients for years. What did it mean to you to be able to obtain and publish this evidence?
It took us eight years to do that research. For me, that’s a huge source of pride. I feel like I’m doing something for my country during my time on active duty, especially for our veterans. We feel like we’re doing the right thing and giving back to these people.
