Years after the Vietnam War, hematologist-oncologist Mikkael Sekeres began treating veterans diagnosed with myelodysplastic syndromes (MDS), a type of blood cancer. Many of these veterans had been exposed to Agent Orange, a combination of herbicides used by the military to clear dense vegetation during the conflict.
While this exposure has been associated with numerous serious illnesses, including various cancers, MDS had not been linked to it until recently. New research published in Blood Advances by Sekeres and his team provides strong evidence connecting Agent Orange exposure to MDS and suggests it can lead to more aggressive forms of the disease.
“I’ve been describing this as my passion project. It’s because I treated these guys over years,” stated Sekeres, who serves as the chief of hematology at the Sylvester Comprehensive Cancer Center at the University of Miami. He noted that many young men exposed to Agent Orange in the 1960s and 1970s later developed MDS in the 2010s and 2020s.
Agent Orange contained herbicides produced by companies such as Monsanto and Dow Chemical, which became tainted with dioxin, a highly toxic compound. Dioxin exposure has led to severe birth defects and an increased risk of various cancers among those affected.
American forces applied Agent Orange across the jungles of Vietnam and neighboring regions, dispersing it from both air and ground, often mixed with kerosene or other fuels to enhance its spread. This exposure prompted the Department of Veterans Affairs to classify several cancers as Agent Orange-related, allowing veterans with these conditions to receive benefits.
MDS, however, was not officially recognized as linked to Agent Orange. Sekeres hopes his research will pave the way for veterans with MDS to receive similar benefits. STAT interviewed Sekeres about this work. The conversation has been edited for brevity and clarity.
How did you first become interested in doing this study?
Sekeres explained that he encountered multiple veterans who, after exposure to Agent Orange, developed MDS. While it was difficult to determine if the disease was directly caused by the exposure or other aging factors, there was a strong biological possibility that Agent Orange was a risk factor. The study aimed to confirm this through a comprehensive registry.
Agent Orange was used as a defoliant in Vietnam, leading to exposure among veterans and locals. While dioxin and fuel in the herbicide were known to cause myeloid malignancies, no formal study had confirmed its connection to MDS until now.
Why was this important for you to do?
The Department of Veterans Affairs acknowledges several cancers as being linked to Agent Orange, qualifying veterans for certain benefits. However, MDS is not yet recognized. Sekeres aims for this study to enable affected veterans to receive deserved disability compensation.
Without this recognition, veterans must present medical proof directly connecting their exposure to their disease, a challenging task. MDS is a severe illness that worsens over time, leading to blood count issues, dependence on transfusions, and increased susceptibility to deadly infections.
How did you do the study?
The research was conducted through the MDS Natural History Study, a detailed investigation spanning nearly a decade. The goal was to examine the progression of MDS from diagnosis across 160 sites nationwide, enrolling patients from the point MDS was suspected. Participants were required to complete a questionnaire about Agent Orange exposure.
What were some of the key findings of the study?
The study found that six percent of participants had been exposed to Agent Orange. Among these, 54% were diagnosed with MDS or its precursor, compared to 37% without exposure. The study also discovered a significant correlation between exposure and the presence of more molecular mutations. Those exposed had more complex forms of MDS, often in high-risk genetic groups, and were more likely to experience disease progression.
Exposure typically occurred in late adolescence or early adulthood, setting individuals on a path to cancer. Early mutations increased the likelihood of further complications as they aged. Additionally, the study highlighted racial disparities, noting that Black veterans were three times more likely than their white counterparts to have been exposed, often serving in frontline positions during the Vietnam War.
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.
Indeed, anyone who came into contact with Agent Orange could be at risk for developing MDS. The study identified distinct genetic mutations in MDS samples from those exposed compared to those not exposed, supporting the likelihood of causality. For individuals in Vietnam, early medical intervention upon noticing abnormal blood counts could lead to earlier diagnosis and more effective treatment, enhancing 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?
The study took eight years to complete, and for Sekeres, it represents a significant achievement. He feels a deep sense of pride in contributing to the welfare of veterans, viewing this work as a way to honor their service and give back to those who served.
