Different Patterns of Oral Mucositis and Microbiota Injury After Total Body Irradiation- Versus Chemotherapy-Based Myeloablative Allogeneic Hematopoietic Cell Transplantation.

PURPOSE

Oral mucositis (OM) is a common complication of allogeneic hematopoietic cell transplantation, causing pain, infections, swallowing/speech impairment, and poor quality of life. We hypothesized that patterns (severity and dynamics) of OM and oral microbiota disruptions may be different after high-dose total body irradiation (TBI)- versus chemotherapy-based myeloablative conditioning.

METHODS AND MATERIALS

We conducted an exploratory study including comprehensive, longitudinal mucositis assessment, paired with supragingival plaque and saliva collection. OM was assessed at baseline and days +7, +14, +21, +28, and +84. Total mucositis score at each timepoint was calculated from objective findings in 2 domains and 9 oral sites using a validated scoring system. Plaque and saliva samples (baseline and days +14, +28, and +84) were profiled using shotgun metagenomic sequencing.

RESULTS

A total of 249 OM assessments were performed and 342 samples were collected from 47 patients (27 chemotherapy-based, 20 TBI-based). Salivary flow rate remained stable in the chemotherapy-based cohort, but steadily declined in the TBI-based cohort, reaching a significantly lower level in the TBI-based cohort at day +84 both compared to baseline and the chemotherapy-based cohort. OM severity peaked at day +7 in the TBI-based cohort versus day +14 in the chemotherapy-based cohort. Day +14 OM was significantly more severe in the chemotherapy-based cohort; other timepoints were not different. Although the cohorts were similar in plaque microbiota composition at baseline, they became significantly different at all post- hematopoietic cell transplantation timepoints. Salivary microbiota composition was not significantly different between the 2 cohorts. Day +84 plaque microbiota diversity was significantly higher in the TBI-based cohort.

CONCLUSIONS

We demonstrated different patterns of OM, microbiota injury, and salivary flow rate after TBI- versus chemotherapy-based conditioning. If validated in future studies, our findings could enhance evidence-based pretransplant counseling on oral toxicity and have implications for short- and long-term oral health in transplant survivors.