Salivary antioxidant enzymes associated with oral toxicity in haematopoietic cell transplantation: An observational study.

BACKGROUND: In haematopoietic cell transplantation (HCT), oral mucositis and xerostomia are related to conditioning-related oxidative stress. The role of salivary antioxidant enzymes in oral toxicity is poorly described. The aim of this study was to verify the association between salivary antioxidant enzymes and oral mucositis and xerostomia in HCT. DESIGN: Saliva from autologous and allogeneic HCT patients (n = 77) was selected before conditioning (T0), during the neutropenia period (T1) and after marrow engraftment (T2). Salivary flow, total salivary proteins, and superoxide dismutase, catalase and glutathione reductase activities were measured. RESULTS: There were no significant differences in salivary flow, total salivary proteins and catalase at the three HCT time points. Glutathione reductase levels were reduced at T1 compared to T0 (P = .013) and T2 (P = .001). Superoxide dismutase levels were increased from T0 to T2 (P = .013). Neither of these enzymes was associated with oral mucositis. Increased superoxide dismutase levels were associated with xerostomia frequency. Levels of this enzyme also showed significant correlation with days of xerostomia in T2 (ρ = .40, P = .002). CONCLUSIONS: Salivary antioxidant enzymes changed before and during early periods after HCT. The increase in salivary superoxide dismutase suggested partial activation of the salivary antioxidant system and was associated with xerostomia.

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.

Retrospective study of the digestive tract mucositis derived from myeloablative and non-myeloablative/reduced-intensity conditionings with busulfan in hematopoietic cell transplantation patient.

Busulfan is a major component of chemotherapy conditioning in hematopoietic cell transplantation (HCT). This alkylating agent is highly toxic at myeloablative doses, exposing HCT patients to risks of mortality. Non-myeloablative (NMA) and reduced-intensity conditioning (RIC) using busulfan have shown impaired toxicity. However, the toxicity of NMA/RIC in the digestive tract is poorly described. This study aimed to characterize the mucositis in the oral cavity (OM), oropharynx/esophagus, and gastrointestinal tract derived from conditionings with myeloablative and non-myeloablative doses of busulfan. We retrospectively retrieved clinical data of HCT patients (n = 100) who underwent myeloablative conditioning (MAC) or NMA/RIC with busulfan. Frequency and time duration of mucositis in the oral cavity and oropharynx/esophagus, diarrhea, and prescription of total parenteral nutrition (TPN) and opioids were also collected. OM severity (p = 0.009) and time duration of mucositis in oropharynx/esophagus (p = 0.022) were frequently higher in MAC than NMA/RIC. A myeloablative dose of busulfan was a risk factor for OM grade ≥ 2 (OR = 4.8, p = 0.002) and for mucositis in oropharynx/esophagus ≥ 5 days (OR = 2.64, p = 0.035). A longer duration of mucositis in the oropharynx/esophagus was also associated with an increase in the prescription of opioids (OR = 7.10, p < 0.001).Overall survival (OS) in MAC was significantly higher than that in NMA/RIC (p = 0.017). No variables related to mucositis interfere significantly in OS. In conclusion, myelosuppression in busulfan-based regimens are predisposed to a high risk for severe OM and to prolonged mucositis in the oropharynx/esophagus.