Background
Agent Orange (AO) exposure may be linked to 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. Although recent studies have not revealed AO associated specific mutations in MDS, other clinical and pathological potential differences have not been well described. In addition, determination of AO exposure is often not reported. Purpose: To assess for differences between AO versus non-AO exposed veterans with MDS.
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 (CPRS) 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). 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, SF3B1, SRSF2, DNMT, ASXL1, and U2AF1, 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. The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.
Conclusions
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.
