The Role of Zinc in Prophylaxis and Treatment of Mucositis in Hematological Malignancies

Treatment-related mucositis impacts over 75% of patients undergoing hematopoietic stem cell transplantation (HSCT). Signs and symptoms of mucositis typically manifest within 5-10 days post-conditioning and can persist for up to three weeks, thus leading to increased infection risk from mucosal barrier injury and challenges in maintaining nutrition status. Currently, there is no routinely utilized pharmacological or dietary agent for treatment or prophylaxis of mucositis. Zinc is an essential trace element that must be obtained via diet with functions such as but not limited to cell proliferation and differentiation, DNA synthesis, wound healing, and regulation of reactive oxygen species with the potential to exert these effects on mucositis. The purpose of this review is to understand available data on the relationship of oral zinc supplementation in prophylaxis and treatment of mucositis in hematological malignancies and thus implications for HSCT. A total of seven studies were selected for this review using PubMed, all of which follow a double-blinded, randomized controlled format performed on 30-140 patients. Inclusion criteria consists of adult human patients (>15 years old), a hematological malignancy diagnosis with subsequent chemotherapy and/or HSCT, administration of zinc prior to and/or during treatment, and publication date during or after 2009. Exclusion criteria consists of studies pertaining to pediatric patients, patients with non-hematological malignancies and studies with a publication date prior to 2009. Six out of seven studies concluded that zinc supplementation is efficacious in the prevention and treatment of mucositis. The incidence, duration and severity of mucositis symptoms can be significantly reduced with as little as twice daily dosing; five out of seven studies indicated a statistically significant reduction in mucositis grades 2-4 after 2-4 weeks of zinc supplementation. Based on these compelling findings, treatment avenues that exert an antioxidant or mucosal-protective effect, such as zinc supplementation, can serve to mitigate mucosal damage generated from conditioning regimens; the potential for zinc to reduce the high rates of mucositis seen in HSCT may be important to reduce infection risk and improve nutrition status. Zinc supplementation can be provided over-the-counter and is available in multiple administrative forms with good tolerance, rendering its use in clinical settings extremely practical. Based on these data, we believe prospective assessments of zinc status in HSCT are warranted and are now being evaluated at Michigan Medicine to identify patients at risk for severe mucositis.