Photobiomodulation (PBM) Provides a Prompt and Near-Resolution Response to Advanced Oral Chronic Graft-Versus-Host Disease (cGVHD) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

Abstract

Background cGVHD is a major complication after allo-HSCT. The oral cavity is frequently affected and may present with painful ulcerations, intraoral discomfort, and limitation to oral intake. While systemic corticosteroids remain first line therapy for moderate/ severe cGVHD, topical and intralesional immunosuppressant (IS)-based therapies have been used with modest effect. PBM, a non-invasive light therapy, appears to promote tissue recovery via direct absorption of cytochrome C oxidase and activation of TGF-β1, and has been used for the prevention and treatment of radiation-induced mucositis in head & neck cancer. However, the effect of PBM therapy in oral cGVHD is currently unknown. Methods We evaluated 7 patients (median age 47) who underwent allo-HSCT (7 PBSC grafts) after myeloablative (n = 3) and reduced (n = 4) conditioning between 09/2015-05/2017. Patients developed moderate (n = 2) or severe (n = 5) oral cGVHD and received PBM (2x/week for 3 weeks) after failure to improve with topical corticosteroid and/or topical tacrolimus therapy +/- intralesional triamcinolone injections and systemic IS. Thor® laser LX2 with wavelengths of 660 nm (visible-red) and 810 nm (near-infrared) was applied extra-orally. The psychometric questionnaire for pain rating (Visual Analogue Scale [VAS], scale 0-10), and oral GVHD (OGVHD) score (severity of erythema, lichenoid changes, ulcers and mucoceles, scale 0-15) were used weekly for the assessment of therapeutic response. Results The baseline oral cGVHD evaluation revealed high VAS (median 7, range 3-8) and OGVHD (median 9, range 6-9) scores. Patients had affected oral cavity that included lichen planus-like changes, ulcers, mucositis, gingivitis, and/or erythema (Fig. 1A-B). The first therapeutic response assessment was obtained 1 week after initiation of therapy and showed improvement in pain by VAS score (median 3). Subsequent assessments were obtained for the duration of PBM therapy and showed overall improvement in the pain scale and healing of the oral cavity (Fig. 1C-D, 2A-B). At the end of treatment, the median VAS score was 2 (range 1-2) and OGVHD was 3 (range 1-4). Treatment was well tolerated, and all patients received the intended number of PBM treatments in the planned period of 3 weeks. No adverse events were reported as related to PBM. Conclusions Advanced oral cGVHD achieved near-complete resolution of pain and oral cavity lesions after PBM therapy. Notable, patients who previously failed to respond to upfront topical and systemic IS treatment achieved high therapeutic response with PBM. Improvement in pain scale was observed 1 week after starting therapy and healing of the oral cavity was observed at 2 weeks. This non-IS treatment appears feasible, safe and promising in oral cGVHD. A prospective study is needed to confirm these preliminary findings.