Agent Orange Exposure and Myelodysplastic Syndrome: A Single VA Medical Center Experience

Background:

Agent Orange (AO) exposure may be linked to the development of myeloid malignancies, including myelodysplastic syndrome (MDS). This is not yet definitive, though, and, unlike several other malignancies, MDS is not yet a service-connected diagnosis for AO exposed veterans. Although recent studies have not revealed AO associated specific mutations in MDS, clinical and pathological potential differences have not been well studied. In addition, determination of AO exposure is often not reported.

Methods:

All veterans diagnosed with MDS at the Cleveland VAMC from 2012-2023 were identified. Prior AO exposure was determined by Military Exposure tab in the EMR and confirmed with direct patient contact. Data collected included age and IPSS-R score at diagnosis; ring sideroblast percentage; mutations (on NGS); progression to AML and overall survival (OS).

Results:

129 veterans were identified, 48 of whom had AO exposure. The mean age was 70.7 years in the AO group and 73.3 in the non-AO group (p=0.098); average IPSS-R score was 3.14 in AO and 2.75 in non-AO group (p= 0.32). 8 (6%) of pts had high risk IPSS-R (4 in each group); 29 (22%) pts had intermed risk (13 AO and 10 non-AO exposed) and 92 pts (71%) were low risk (31 AO and 61 non-AO). In the AO group 4/48 (8.3%) progressed to AML vs 10/81 (12.3%) in the non-AO group; median OS was 39 months in AO vs 33 months in non-AO group (p=0.93). The most common mutations seen were TP53 (17%), SF3B1 (21%), SRSF2 (23%), DNMT (10%), ASXL1 (11%), and U2AF1 (11%), with no differences between the 2 groups. 50% of those in the AO group had 2 or more genetic mutations vs. 61% for the non-AO group. Average variant allele frequency (VAF) was 40.2% in the AO group vs. 44% in the non-AO group. 9/48 (19%) of pts in the AO group met criteria for MDS-RS vs 12/81 (15%) in the non-AO group (p= 0.74). The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.

Conclusion:

This small retrospective study did not reveal statistically significant differences between AO vs non-AO exposed veterans with MDS, in terms of age at diagnosis, IPSS-R score, RS %, mutations (type, number or VAF load), progression to AML or OS. There were trends for AO exposed veterans presenting at a younger age and having a lower rate of progression to AML. Although we did not find any phenotypic or genotypic differences this was not a study of causality and does not exclude AO being associated with increased risk for MDS.

No relevant conflicts of interest to declare.