Examining Potential Biomarkers for Early Detection of Chronic Graft-Versus-Host Disease

Seeking to improve early detection of chronic graft-versus-host disease (cGVHD), Ankit Shah and colleagues tested if early detection of metalloproteinase-9 (MMP-9) or dry eye (DE)—assessed via the Dry Eye Questionnaire 5 (DEQ-5; range: 0–22)—could be viable for predicting development of cGVHD or severe DE symptoms In their poster, presented at the Transplantation & Cellular Therapy 2022 Tandem Meetings, the researchers reported that “DEQ-5 and MMP-9 assessment at [day] 100 did not predict the development of cGVHD or severe DE symptoms” in their small cohort.

The study included 25 participants with underlying malignancies including acute and chronic lymphocytic leukemia, acute myeloid leukemia, follicular lymphoma, myelodysplastic syndrome, and aplastic anemia. Patients were screened with the DEQ-5 and bilateral InflammaDry (a point-of-care test that detects MMP-9) at approximately 100 days after they underwent hematopoietic cell transplantation (HCT). Further DEQ-5 surveys were performed at three, six, and nine months from the initial testing. Researchers used Cox regression models to determine if the presence of MMP-9 or a DEQ-5 score of six or greater had prognostic value for cGVHD or severe DE symptoms.

Reportedly, 28% of patients (n = 7) developed cGVHD throughout the mean follow-up period of 128 ± 63 days (range: 45–216). At the initial testing, MMP-9 was detected in at least one eye in 32% of patients (n = 8), while 20% (n = 5) had a DEQ-5 score ≥6. The authors noted that the presence of a positive MMP-9 or a DEQ-5 score ≥6 at [day] 100 were not predictive of developing cGVHD (MMP-9: hazard ratio (HR) = 1.53; p = 0.58; DEQ-5: HR = 1.00; p = 1.00) Furthermore, neither variable was shown to predict severe DE symptoms over time. The authors did find that DEQ-5 scores tended to increase over time regardless of cGVHD development.

The findings from the study ultimately showed that MMP-9 and DEQ-5 scores were not feasible as predictive markers for the onset of chronic graft-versus-host disease after allogeneic HCT, and they reemphasized the need for predictive biomarkers for earlier detection of cGVHD.