Soldiers deploying to the Gulf War make their way to a plane in 1990 at Volk Field, WI in 1990. A new study found that those veterans were at an especially high risk of myeloproliferative neoplasms. (MPNs because of environmental exposures) U.S. Army file photo from Fort McCoy Public Affairs Office
WASHINGTON, DC — A study of almost a half-million veterans has found for the first time a link between environmental exposures during military service and the development of myeloproliferative neoplasms (MPNs).
MPNs—including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF)—are a group of rare, heterogeneous and acquired clonal stem-cell disorders, which lead to uncontrolled proliferation of myeloid cells and complications including arterial and venous thrombosis, bleeding, cardiovascular disease and potentially the development of leukemia. The study’s findings could open MPNs to be recognized as presumptive conditions under the Promise to Address Comprehensive Toxics (PACT) Act, suggested Maneesh R. Jain, MD, one of the study’s leaders.
Jain, a hematologist/oncologist at the Washington, DC VAMC, became intrigued with a possible connection between military exposures and MPN when three of his female patients who had served in the Korean War were diagnosed with MPNs. All three believed their disease was related to exposure to Agent Orange (a tactical herbicide used by the U.S. military for the control of vegetation), as were a number of other veterans they communicated with thought an MPN advocacy group.
To better understand a possible connection, Jain and colleagues at Georgetown University and George Washington University, including hematology/oncology fellow Andrew Tiu, MD, turned to the DoD and VA Infrastructure for Clinical Intelligence (DaVINCI). DaVINCI is an electronic network that provides a consolidated view of electronic medical record data for both service members and veterans.
Their retrospective cohort study, published in the American Journal of Hematology, included 65,425 Korean War era veterans, 211,927 Vietnam War era veterans, and 214,007 Persian Gulf War era veterans from Jan. 1, 2006, to Jan. 26, 2023. Veterans with MPN, thrombosis, bleeding, and cardiovascular risk factors were identified through ICD-9 and -10 codes. Illinois was selected as the state of residence, as it best mirrored the demographics of the entire U.S. cohort in terms of age, race, ethnicity and educational attainment according to the American Community Survey from the U.S. Census Bureau.1
“The Promise to Address Comprehensive Toxics (PACT) Act expanded U.S. Veterans’ health care and benefits for conditions linked to service-connected exposures (e.g., Burn Pits, Agent Orange),” the researchers explained. “However, myeloproliferative neoplasms (MPN) are not recognized as presumptive conditions for veterans exposed to these toxic substances.”
Among all 491,359 service- and nonservice-connected veterans from Illinois, 1,279 cases of ET, 1138 cases of PV, and 103 cases of PMF were identified. Among the different service-connected exposures, veterans from the Persian Gulf War era had the highest risk of developing MPN compared with veterans from Korean and Vietnam War eras, the researchers found. The study found that Vietnam War-era veterans also had a higher risk of MPN development compared with Korean War-era veterans, HR 1.97, 95% CI 1.77-2.21, p < 0.0001.
Persian Gulf War-era veterans had a younger age of MPN diagnosis and lower frequency of CVD risk factors compared with Vietnam and Korean War era veterans and had a higher risk of arterial thrombosis, venous thrombosis and bleeding compared to the other two groups of veterans. Further, for Persian Gulf War era veterans, the yearly age-adjusted MPN incidence per 100,000 population was 10.5—approximately triple the age-adjusted rate of 3.5 in the general population. Persian Gulf era veterans with MPN also had a 5.55 times lower chance of survival compared with Korean War era veterans with MPN and 2.39 times lower chance of survival compared with Vietnam War era veterans with MPN, the researchers reported.
Surprising Findings
The study’s findings were surprising, particularly considering the relatively young age of the Persian Gulf War era veterans and the fact that most patients with MPN are diagnosed in their 60s or 70s, Jain said. Further, the researchers were initially interested in an association between Agent Orange and MPN, but their findings suggested that burn pits—which were commonly used in Iraq, Afghanistan and other overseas locations to dispose of waste collected on military bases—presented a greater risk. Like Agent Orange, burn pit exposure has been associated with several health problems.
“We were all going down this lane that really Agent Orange was going to be the one that the highest association with MPN,” said Jain. “Persian Gulf was kind of thrown into the data set, but there was not a lot of discussion about burn pits, the Persian Gulf and MPN. But it is definitely worth exploring because this is a very young group and this is something they need to be aware of—that exposure can lead to this disorder. I think that is a finding worth getting out there, but it was not really our main intention when we started.”
Jain added that the researchers’ goal is to get MPNs classified as presumptive disorders under the PACT Act, meaning they will automatically presumed to be caused by one’s military service. Veterans who have a presumptive condition don’t need to prove that their service caused the condition, only that they meet the service requirement for the presumption.
In the meantime, Jain encourages veterans who are diagnosed with MPN to bring the study to their doctor’s attention and for physicians to consider wartime exposures in veterans diagnosed with MPNs.
Tiu concurs. “If veterans from the Persian Gulf War develop blood clots or arterial or venous thrombosis, their physicians should have some sort of suspicion and examine them more closely to see if they have any myeloid lineage disorder, which is an MPN,” he explained. “If they have elevated blood counts, [their physicians] should look at them closely. Is this a reactive process, or is this something more of a bone marrow pathology that needs further evaluation?”
Because their study was a retrospective cohort study, not an epidemiological study, it has limitations—including the fact that only Illinois veterans were studied—Tiu said, adding that future studies should validate their findings.
- Tiu A., McKinnell Z, Liu S, Gill P., et al. (2024). Risk of myeloproliferative neoplasms among U.S. Veterans from Korean, Vietnam, and Persian Gulf War eras. American Journal of Hematology, 10.1002/ajh.27438. Advance online publication. https://doi.org/10.1002/ajh.27438
