Risk factors and implications of oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation

Abstract

Background Oral mucositis (OM) is a common toxicity of stem cell transplantation (SCT). We sought to evaluate OM burden, risk factors, and implications in a cohort of allogeneic‐SCT recipients. Methods This was a single‐center study including 115 adult allogeneic‐SCT transplanted between 2016 and 2018 for various hematological conditions. Conditioning intensity was categorized as myeloablative (MAC, 39%), reduced intensity (34%), or reduced toxicity (RTC, 27%) in patients conditioned with fludarabine‐treosulfan. OM was prospectively graded using the Common Terminology Criteria for Adverse Events (v.4.0) system. Results Moderate‐to‐severe OM (grade 2‐4) was experienced by 60% of patients. In a univariate analysis, younger age (P = .023), lower body mass index (P = .01), recent smoking (P = .08), recent antibiotics exposure (P = .018), MAC (P < .001), and methotrexate (P = .009) were associated with moderate‐to‐severe OM. In a multivariable logistic regression model, conditioning and graft‐versus‐host disease prophylaxis remained significant. OM risk was lowest with RTC (RTC vs MAC: odd ratio [OR] 0.05, P < .001), and recent antibiotic exposure trended toward increased risk (OR 1.88, P = .168). OM was associated with longer hospitalization, delayed neutrophil engraftment, and gastrointestinal‐related infections. Conclusion Oral mucositis remains a leading SCT complication. Treosulfan‐based conditioning has low mucosal toxicity and is appealing given previous reports on its high efficacy.

Incidence and Clinical Characteristics of Oral Mucositis in Allogeneic Hematopoietic Stem Cell Transplantation with Post-transplant Cyclophosphamide Treatment

“…However, to the best of our knowledge, the incidence and severity of OM among patients with PTCy-based allogeneic HSCT have been unclear to date. [19] In our cohort of 140 cases who received transplants with PTCy treatment, the incidences of any OM (82.9%) and severe OM (28.6%) were comparable to those in previous reports, in cases using a traditional transplant regimen other than PTCy (47.2-100% and 2.5-60.9%, respectively). [1, 20-25, 19, 26] PTCybased prophylaxis was reported to show a better safety pro le compared with ATG and was associated with reduced severity of mucositis.…”

“…[19,[29][30][31] However, the incidence of severe OM in this study was lower than that in previous reports. [1] This might be re ective of the relatively younger patients, more frequent use of udarabine-based reduced toxicity conditioning regimens, [19] and the standardized and intensi ed oral care protocol. Notably, mismatched donors and lack of ATG in the GVHD prophylaxis regimen were signi cantly related to severe OM in multivariate analysis.…”

Pre-therapy fasting slows epithelial turnover and modulates the microbiota but fails to mitigate methotrexate-induced gastrointestinal mucositis

“…Experience in our group suggests that, despite body weight-dependent dosing, reduced body weight at the time of MTX can worsen toxicity outcomes, aligning with low body mass index as a predictor of mucositis. 27 Weight-matched rats were allowed to gain additional weight during acclimatization, to ensure that they were a comparable weight to control (fed) rats after 48 h of fasting. Contrary to our hypothesis, this did not affect the ability of pre-therapy fasting to prevent MTX-induced GI-M, indicating that it is more likely that the lack of fat stores masks the protective cellular and microbial mechanisms induced by fasting.…”

“…These results align with existing preclinical findings 9 and clinical risk factors, with antibiotic use prior to chemotherapy associated with increased GI-M severity. 10 Similarly, while probiotics have shown some benefits in mitigating the severity of MTX associated GI-M, 11 translational success is variable. 12 These findings have prompted an enthusiastic investigation of how the microbiota can be best modulated to improve MTX outcomes.…”

Patterns of salivary microbiota injury and oral mucositis in recipients of allogeneic hematopoietic stem cell transplantation

“…Oral mucositis (OM) is a common debilitating toxicity of cancer therapy, including hematopoietic stem cell transplantation (HSCT). [1][2][3] Chemoradiotherapy-induced damage to epithelial stem cells, release of inflammatory cytokines, and activation of the innate immune system drive OM pathophysiology. 4 Since commensal bacteria facilitate immune responses, 5 the oral microbiome may play a role in OM pathogenesis.…”