Persian Gulf War Service Linked to High Rates of Myeloproliferative Neoplasms

by Mary Anne Dunkin | Sep 15, 2024

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

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Risk of myeloproliferative neoplasms among U.S. Veterans from Korean, Vietnam, and Persian Gulf War eras

July 18, 2024

Andrew TiuZoe McKinnellShanshan LiuPuneet GillMartha AntonioZoe ShancerNandan SrinivasaGuoqing DiaoRamesh SubrahmanyamCraig M. KesslerManeesh Jain

Abstract

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). However, myeloproliferative neoplasms (MPN) are not recognized as presumptive conditions for Veterans exposed to these toxic substances. This study evaluated the development of MPN among U.S. Veterans from the Korean, Vietnam, and Persian Gulf War eras. This retrospective cohort study included 65 425 Korean War era Veterans; 211 927 Vietnam War era Veterans; and 214 007 Persian Gulf War era Veterans from January 1, 2006, to January 26, 2023. Veterans with MPN, thrombosis, bleeding, and cardiovascular risk factors were identified through ICD-9 and -10 codes. Veterans from the Persian Gulf War era had the highest risk of developing MPN compared with Veterans from the Korean and Vietnam War eras, hazard ratio (HR) 4.92, 95% confidence interval (CI) 4.20–5.75 and HR 2.49, 95% CI 2.20–2.82, both p < .0001, respectively. 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 < .0001. Persian Gulf War era Veterans were diagnosed with MPN at an earlier age, had higher risks of thrombosis and bleeding, and had lower survival rates compared with Korean War and Vietnam War era Veterans. This study reinforces evidence that environmental and occupational hazards increase the risk of clonal myeloid disorders and related complications, impacting overall survival with MPN. Limitations include the inability to confirm clonality and fully verify deployment and exposure status.

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