Oral chronic graft-versus-host disease symptom experience and cytokine correlates in survivors after transplantation for hematologic malignancies

Abstract

19510 Background: Oral chronic graft-versus-host-disease (cGVHD) is a frequent, clinically significant sequela of hematopoietic stem cell transplant (HSCT). No optimal treatment exists; molecular pathogenesis remains unclear. This descriptive study assessed stomatitis, oral pain, and dry mouth severity, and correlations with proinflammatory cytokine levels in stimulated submandibular saliva samples from cGVHD patients. Methods: Subjects were enrolled in the NCI sponsored cGVHD natural history protocol. Stomatitis severity was assessed with the Oral Mucositis Rating Scale (OMRS) (0–103); oral pain and dryness were self-reported via VAS (0–10). Saliva samples were collected on ice, stored at -80°C, centrifuged at 4000xg for 10 minutes at 4°C, and supernatant retained. Salivary TNFa, IL1a, and IL6 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) (R & D Systems, Minneapolis, MN). Results: Adult male and female subjects (N = 42) with cGVHD after HSCT primarily for hematologic malignancies were prescribed systemic (n = 34) and/or topical (n = 4) immunosuppressive agents, and opioids (n = 19). All subjects had mild to moderate stomatitis (OMRS mean = 18.38; range = 2.0 to 46) with erythema (n = 40), lichenoid (n = 32), and ulceration (n = 25). Mild to severe oral dryness (43%) (mean = 2.56; range 0 to 10) was more clinically significant than oral pain (8%) (mean = .13). Salivary cytokine concentrations were: TNFa (n = 32; mean = .31 pg/mL; range 0 to 2.8); IL1a (n = 29; mean = 85.23 pg/mL; range = 13 to 250), and IL6 (n = 29; mean = 2.48 pg/mL; range 0.100 to 10.00). Significant associations by Pearson Product Moment correlation were: TNFa and erythema (r = .34; p < .05); IL1a and oral dryness (r = .40; p < .05); IL6 and OMRS (r = .49; p < .01), erythema (r = .63; p < .001), and ulceration (r = .38; p < .05). Conclusions: Paucity of oral pain may be related to appropriate management. Moderate to strong correlations between salivary TNFa and IL6 and oral cGVHD severity, and IL1a and oral dryness suggest utility as correlates of disease severity and symptom, and monitors of therapeutic response to investigational agents. No significant financial relationships to disclose.