Trial Information

Evaluation of Efficacy and Mechanisms of Topical Thalidomide for Chronic Graft-Versus-Host-Disease Related Stomatitis

Oncology patients undergoing allogeneic bone marrow/peripheral blood stem cell transplant
(HSCT) frequently experience an allo-immune condition termed graft-versus-host-disease
(GVHD). The pathogenesis of GVHD derives from an immune attack mediated by donor T-cells
recognizing antigens expressed on normal tissues of the patient. This condition occurs in
HSCT rather than autologous BMT because of disparities in minor histocompatibility antigens
between donor and recipient, inherited independently of HLA genes (Lazarus, Vogelsang, and
Rowe, 1997). GVHD may be conceptualized as a cytokine storm stemming from an outpouring
of endogenous cytokines resulting in many tissue effects (Lazrarus et al, 1997). Oral
chronic GVHD (cGVHD), which is classically diagnosed as a late complication of HSCT
occurring more than 100 days post transplant, presents with tissue atrophy and erythema,
lichenoid changes (hyperkeratotic striae, patches, plaques, and papules) and
pseudomembranous ulcerations typically occurring on the buccal and labial mucosa and the
lateral tongue, mucoceles due to inflammation of minor salivary glands, and xerostomia
(Lloid, 1995). The ulcerative phase often leads to a cascade of negative sequelae including
oropharyngeal pain, critical treatment alterations or cessation, diminished capacity for
food intake, and decreased quality of life. We hypothesize that the mechanisms of tissue
injury occurring at the mucosal level leading to cGVHD-related stomatitis are similar to
other types of stomatitis, such as chemotherapy-related and aphthous stomatitis, and are
therefore amenable to treatment with anti-inflammatory strategies.

Optimal treatment strategies for cGVHD-related ulcerative stomatitis and related
oropharyngeal pain have not been established. Therefore, there is a critical need to examine
the pathogenesis of and to evaluate interventions for cGVHD-related ulcerative stomatitis
and related acute oropharyngeal pain in the randomized controlled clinical trial setting to
both advance the science of cancer treatment-related oral complications and to improve
patient care. Therefore, the purpose of this study is to elucidate the role of inflammation
in GVHD-related ulcerative stomatitis by testing the efficacy of topical thalidomide on the
resolution of cGVHD-related stomatitis and related oropharyngeal pain. The actions of
thalidomide, which include inhibition of the release of tumor necrosis factor-alpha (TNFa)
and resultant alteration of the inflammatory cascade, may provide insight into the role of
local mucosal inflammation in cGVHD-related stomatitis.