Viral loads and antiviral resistance of herpesviruses and oral ulcerations in hematopoietic stem cell transplant recipients

Abstract

Ulcerative oral mucositis and infection are frequent complications in hematopoietic stem cell transplant (HSCT) recipients. The aim of this study was to investigate the relationship between oral ulcerations and HSV-1, EBV and CMV excretion and the presence of aciclovir-resistant HSV-1 strains in HSCT recipients. This prospective observational study included 49 adult patients who underwent allogeneic HSCT. In total, 26 patients received myeloablative and 23 received non-myeloablative conditioning. Ulcerations on non-keratinized and keratinized oral mucosa were scored and oral rinsing samples were taken twice weekly. Viral loads were determined by real-time PCR. Samples from patients remaining HSV-1 positive despite antiviral treatment were studied for resistance to antivirals. Having an HSV-1 or EBV DNA --positive sample was a significant predictor for ulceration of keratinized mucosa. HSV-1 was a significant predictor for ulcerations on non-keratinized mucosa as well. Persistent HSV-1 infection occurred in 12 of 28 patients treated with antiviral medication and aciclovir-resistant HSV-1 was found in 5 persistent infections. In conclusion, HSV-1 is a predictor of ulcerations on non-keratinized as well as keratinized oral mucosa following HSCT. The role of EBV deserves further study. Persistent HSV-1 replication despite antiviral treatment is common and is due to resistance in 18% of treated patients.

Herpesviruses and oral ulcerations in hematopoietic SCT recipients

“…When assessing clinical significance of the post-transplant viremia, we revealed a clear dependence between HSV viremia and oral mucositis grade, in accordance with results reported by van der Beek et al 1 Indeed, we have found a significant increase in oral ulceration rates among HSV-positive vs HSV-free cases (100% vs 75%, respectively; Po0.02).…”

“…We have read with great interest an article by van der Beek et al 1 published in Bone Marrow Transplantation. The authors reported that HSV-1 shedding in oral fluid after hematopoietic SCT (HSCT) is a significant predictor for oral mucosal ulcerations in adult patients, thus being a promising marker of the epithelial lesion.…”

Oral shedding of human herpesviruses in patients undergoing radiotherapy/chemotherapy for head and neck squamous cell carcinoma is not affected by xerostomia

“…There was statistically significant difference compared to all other excreted viruses ( p  < 0.001). Ambinder et al and Van der Beek et al stated that 25%–98% of the saliva samples of immunosuppressed patients were positive for EBV as a result of chemotherapy [14,39]. According to the authors, all cancer patients presented some degree of immunosuppression, which may explain the higher rates of EBV excretion.…”

“…The association between viral infections and oral complications from RT are poorly reported in the literature, and the existing results are contradictory. Some authors suggest that RT may cause a transient state of immunosuppression, thus contributing to reactivation of herpesviruses [14]. Until this moment, there have been few studies in the literature relating oral shedding of human herpesviruses to xerostomia in patients undergoing RT associated with chemotherapy [15–17].…”

Severe herpes simplex oral mucositis in a patient with non-Hodgkin’s lymphoma after autologous stem cells transplantation – Case Report

“…The carriers of of HSV-1 were found in 80% of patients before HSCT. Researchers state that the persistence of HSV-1 infection in spite of the treatment with acyclovir, affected approximately 18% of patients, and probably was the result of a mutation located in a TK gene (thymidine kinase) [7,8].…”