Is Salivary Busulfan the Cause of Oral Mucositis and the Changes in Salivary Antioxidant Enzymes After Hematopoietic Cell Transplantation?

Background: To determine whether the busulfan (Bu) present in saliva during hematopoietic cell transplantation (HCT) conditioning correlates with oral mucositis and the changes in salivary antioxidant enzymes. Methods: Bu levels in the plasma and saliva of 19 patients who received HCTs were quantified. Salivary flow and salivary superoxide dismutase and catalase activities were measured during HCT. For the toxicity analysis of salivary Bu, an in vitro assay was conducted by exposing human keratinocytes to artificial saliva containing Bu. Results: Plasma and salivary Bu concentrations were very similar (rho = 0.92,P< 0.001). Salivary Bu concentration correlated with the degree of oral mucositis severity (rho = 0.391,P= 0.029) and was inversely proportional to salivary superoxide dismutase and catalase activities (rho = -0.458,P= 0.036; rho = -0.424,P= 0.043, respectively). Cells exposed to Bu-containing saliva had fewer viable cells (P< 0.01) and more apoptotic cells (P= 0.001) than those exposed to non-Bu-containing saliva. Conclusions: Bu found in saliva during HCT conditioning was correlated with severe oral mucositis and the reduction in salivary antioxidative activity. Furthermore, Bu can be toxic to keratinocytes.