Decades after the Vietnam War, hematologist-oncologist Mikkael Sekeres began seeing veterans in his clinic with myelodysplastic syndromes, a group of blood cancers known as MDS. Many of the vets had been exposed to Agent Orange, a blend of herbicides that the military used to peel back dense foliage during the war.
This exposure has long been linked to many serious diseases, including several cancers, but not MDS — until now. In data published this month in Blood Advances, Sekeres and his colleagues were able to provide clear evidence that Agent Orange exposure is linked to MDS and can cause earlier, more aggressive disease.
“I’ve been describing this as my passion project. It’s because I treated these guys over years,” said Sekeres, who is the chief of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami. “These mostly young guys were exposed in the ’60s and ’70s, then developed MDS in the 2010s, 2020s. I had a number of vets who were exposed to Agent Orange.”
One of the herbicides in Agent Orange, produced by companies like Monsanto and Dow Chemical, became contaminated during the production process with an extremely toxic compound called dioxin. Dioxin has caused severe birth defects in children of people exposed to the toxin, and it can also significantly increase the risk of developing several different kinds of cancer.
American soldiers sprayed Agent Orange over the jungles of Vietnam and nearby countries from the air and from the ground, often mixing it with kerosene or fuel, another carcinogen, to help disperse it. That exposure has led the Department of Veterans Affairs to recognize several cancers as linked to Agent Orange, which qualifies veterans with those specific conditions to receive benefits from the VA.
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But not MDS, Sekeres said. He hopes this research will provide a path for affected veterans to receive benefits. STAT spoke with Sekeres about the work. This interview has been edited for length and clarity.
How did you first become interested in doing this study?
I had a number of veterans who were exposed to Agent Orange and developed MDS. Bad things happen to folks as they age, so it was hard to know if this was because of the Agent Orange or if it was unrelated. The biological plausibility of this being a risk factor for eventually developing MDS is absolutely there, and what remained was getting an adequate registry for demonstrating this.
It was used as a defoliant in Vietnam. Veterans were exposed. Folks in Vietnam were exposed to it. The dioxin and the fuel have been linked to myeloid malignancies. We’ve long suspected that it could lead to MDS, but the military and no formal study had ever made the connection before.
Why was this important for you to do?
The Department of Veterans Affairs already recognizes several cancers as being presumptively linked to Agent Orange. That qualifies veterans to get certain benefits. But the VA doesn’t yet recognize MDS as presumptively linked to Agent Orange. My hope and my goal with this study is to enable these aging veterans to finally receive the disability compensation they deserve.
Right now, without the Department of Veterans Affairs recognizing this connection, my patients must try to provide medical evidence showing a direct service connection between the exposure and their disease, which is almost impossible. It’s a terrible disease. As MDS gets worse, blood count abnormalities get worse. People get dependent on red blood cell transfusions and become prone to bleeding and infection, which can be deadly.
How did you do the study?
We did it through the MDS Natural History Study. It’s this really cool study we conducted over almost a decade. The goal was to study the natural history of MDS from the moment people are diagnosed with it from 160 sites all around the country, and we enroll them from the moment MDS is suspected. That means they have some sort of blood anomaly and were referred to a hematologist. About half had MDS or a precursor, and half did not.
We were very deliberate in making sure that folks answered a questionnaire about whether they were exposed to Agent Orange.
What were some of the key findings of the study?
Six percent of people enrolled in this study had exposure to Agent Orange. Among those exposed to Agent Orange, 54% were eventually found to have MDS or precursor versus 37% of them were not found to have MDS or a precursor condition. In our study, it’s significantly associated with a person having more molecular mutations as well. Not only did they have MDS, but more complex MDS in poor or very poor genetic risk groups. We actually showed that folks who had Agent Orange exposure were more likely to have progression of their MDS.
That makes sense. They were exposed in late teens or early 20s. I call it the grim rose path towards cancer. You get your first mutation at a young age; then you’re more likely to get it at a younger age. By the time we detect it, it’s more likely to have complications.
The interesting thing also, Black race kept coming up. They had three times the likelihood of exposure than whites. Blacks who served in Vietnam were in more vulnerable positions like the frontlines, where they were more likely exposed to Agent Orange.
Mikkael SekeresCourtesy Sylvester Comprehensive Cancer Center
Are the results generalizable beyond the study population? American soldiers weren’t the only ones exposed to these toxins. The civilian population of Vietnam and neighboring countries also were exposed to, and suffered from, Agent Orange.
Absolutely. Anyone who had contact with Agent Orange is potentially at risk of developing MDS. We were able to identify very distinct genetic mutations in the MDS samples in those exposed to Agent Orange and those who were not. You have this building of facts that makes it much more likely in establishing causality.
If I were Vietnamese and exposed and started to develop a blood count that’s abnormal, I would be quick to seek medical care and see if it can be diagnosed at an earlier stage. Treatment is more effective, and you can help people enjoy a better quality of life.
You’d been seeing these patients for years. What did it mean for you to be able to get this evidence and publish it?
It took eight years for us to do the study. For me, it’s an enormous sense of pride. I feel like I’m doing something for my country, particularly for the veterans when they were serving. We feel like we’re doing the right thing and giving back to these folks.
