Elevated Likelihood of Infectious Complications Related to Oral Mucositis After Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis of Outcomes and Risk Factors

• Published in: Cancers Vol. 17; no. 16; p. 2657
• Main Authors: Eichhorn, Susan, Rudin, Lauryn, Ramasamy, Chidambaram, Varsani, Ridham, Padhi, Parikshit, Nassour, Nour, Meleveedu, Kapil, Epstein, Joel B., Semegran, Benjamin, Pili, Roberto, Satheeshkumar, Poolakkad S.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.08.2025; MDPI
• Subjects: Autografts; Autoimmune diseases; Bacterial infections; Bendamustine; Bias; Cancer therapies; Case reports; Chemotherapy; Clinical trials; Complications and side effects; Development and progression; Discriminant analysis; Hematopoietic stem cells; Immunocompromised hosts; Infection; Infections; Leukocytes (neutrophilic); Medical research; Medical Subject Headings-MeSH; Medicine, Experimental; Meta-analysis; Methotrexate; Mucosa; Mucositis; Multiple myeloma; Multivariate analysis; Neutropenia; Observational studies; Palifermin; Patient outcomes; Patients; Polymorphism; Population; Qualitative research; Quality of life; Renal function; Risk assessment; Risk factors; Statistical analysis; Stem cell transplantation; Stem cells; Stomatitis; Systematic Review; Transplantation; Validation studies; United States; oral mucositis; meta-analysis; hemopoietic stem cell transplants; risk factors; systematic reviews; outcomes
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers17162657

Mucositis involving the gastrointestinal, vaginal, and nasal mucosa is one of the primary dose-limiting toxicities of hematopoietic stem cell transplantation (HSCT) and its conditioning regimen. The oropharyngeal mucosa is commonly affected, which can be detrimental to patient health and quality of life. Despite its significant prevalence and deleterious effects, we have an inadequate understanding of the risk factors and outcomes associated with oral mucositis (OM). We performed a literature search through PubMed and EBSCO (inception to 31 March 2024) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data was extracted from eligible studies using a pre-specified data extraction form. Quality of the data was assessed using the Newcastle-Ottawa Scale for non-randomized, observational studies and the Cochrane Collaboration Tool for randomized controlled trials. Our initial search identified 1677 articles, 34 of which were included in our study. Of those 34, 30 were included in the qualitative assessment of clinical risk factors in the development of OM, and 4 were included in the meta-analysis assessing the relationship between OM and infectious complications following HSCT. Across both HSCT modalities and cancer cohorts, female sex and high-intensity conditioning were common risk factors in the development of OM. When stratified by allogeneic and autologous HSCT, methotrexate, younger age, and longer duration of neutropenia were associated with increased OM risk in allogeneic HSCT recipients, while renal dysfunction, HSV-1 reactivation, and longer neutrophil engraftment were associated with increased OM risk in autologous HSCT recipients. Longer neutrophil engraftment was a common risk factor across different cancer cohorts; however, renal dysfunction was a distinct risk factor for OM in multiple myeloma patients. Additionally, our meta-analysis revealed that patients with OM have an increased risk of developing infectious complications following HSCT compared to those without OM, with an odds ratio of 3.84 (95% CI: 2.51–5.86). The development of OM is related to various risk factors, and individuals with OM are at greater risk of infectious complications. Knowledge of these risk factors and outcomes will help clinicians identify high-risk individuals, prevent OM, and protect an immunocompromised population from subsequent life-threatening complications.