Oral Symptom Intensity, Health-Related Quality of Life, and Correlative Salivary Cytokines in Adult Survivors of Hematopoietic Stem Cell Transplantation with Oral Chronic Graft-versus-Host Disease

Abstract

Oral chronic graft-versus-host disease (cGVHD) is a frequent, clinically significant sequela of allogeneic hematopoietic stem cell transplant (HSCT). This study was designed to elucidate relationships among clinical characteristics of oral cGVHD and related oral pain and oral dryness, salivary proinflammatory cytokine IL6 and IL1α concentrations, and health-related quality of life (HRQL). An understanding of the characteristics and correlates of oral cGVHD manifestations and related symptoms such as dryness is fundamental to the development of therapeutic interventions. Methods: Oral cGVHD severity was assessed with the Oral Mucositis Rating Scale (OMRS). Oral pain and perceived oral dryness intensity were self-reported via a visual analogue scale and a numeric rating scale respectively. HRQL was assessed with the Functional Assessment of Cancer Therapy-General (FACT-G). Salivary IL1α and IL6 concentrations were measured by enzyme-linked immunosorbent assay (R & D Systems, Minneapolis, MN). Results: All 42 adult subjects (male 59%) had clinician-assessed oral cGVHD by OMRS scale (mean = 18.38 ± 12.99; range = 2 to 46). Oral dryness (43%) (mean = 2.56 ± 3.45; range = 0 to 10) was more prevalent than oral pain (8%) (mean = 0.13 ± 0.47). Salivary IL6 was associated with oral cGVHD severity (r = .49; p < .01), oral ulceration (r = .38; p = .04), and erythema (r = .63; p < .01). FACT-G total, and physical and emotional well-being subscale scores were meaningfully lower than US population normative values. Participants with more severe oral cGVHD manifestations had significantly inferior social/family well-being (r = −.49; p < .01). Oral dryness was associated with higher salivary IL1α (r = .41; p = .04), and controlling for cGVHD severity, with lower health-related quality of life (r = −.41; p = .03). Subjects with moderate to severe oral dryness tended to report the poorest overall HRQL. This study provides preliminary evidence of the relationship between oral dryness and HRQL, the contribution of oral cGVHD to inferior HRQL, and the association between IL6 and oral cGVHD overall severity, ulceration and erythema. The high prevalence of oral dryness and its relationship to HRQL in a sample of patients with oral cGVHD underscores the importance of improving our evaluation and management of this symptom in long-term survivors of allogeneic HSCT. The positive association seen between IL6 and oral sGVHD overall severity, and erythema, as well as the positive trend seen with oral ulceration, warrant further exploration of this cytokine as a potential biomarker of active oral cGVHD.

Long-term oral complications of allogeneic haematopoietic SCT

“…Only a minority, 15% (n ¼ 13), complained that xerostomia adversely impacted on their quality of life. This finding, in contrast to recent studies showing that moderate to severe xerostomia was associated with the poorest levels of overall health-related quality of life, 19 is difficult to explain but may relate to differences in measures used to assess xerostomia and quality of life.…”

Oral Chronic Graft-vs.-Host Disease Characterization Using the NIH Scale

“…Oral cGVHD has also been associated with altered taste and intolerance for spicy and acidic foods (Schubert and Correa, 2008). Oral dryness is consistently associated with poor quality of life (Fall-Dickson et al, 2010). In this study, patients with oral cGVHD reported having higher Lee Symptoms Scale bother scores from avoidance of foods as well as from ulcerations and also reported having greater mouth pain and sensitivity as compared with patients without oral cGVHD.…”

Oral cGVHD screening tests in the diagnosis of systemic chronic graft-versus-host disease

“…Studies have shown that immunological mechanisms of cGVHD include donor-derived alloreactive T lymphocytes, autoreactive T lymphocytes and regulatory T lymphocytes as well as the dysregulation of cytokine expression [13]. The first grading scheme for the severity of systemic cGVHD was proposed in 1980 based on data from 20 subjects classifying the disease as limited when it affects skin and/or liver or as extensive when present skin involvement or localized skin involvement or hepatic dysfunction caused by chronic GVDH in combination with histological changes of the liver that showed chronic aggressive hepatitis, bridging necrosis or cirrhosis, involvement of the eye, histologically proven involvement of minor salivary glands or oral mucosa on labial biopsy, or proven involvements of any other target organ [5].…”