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Systematic Review

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

1
Boston Medical Center, Boston, MA 02118, USA
2
Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
3
Carol and Ray Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, CT 06030, USA
4
School of Dental Medicine, University at Buffalo, Buffalo, NY 14215, USA
5
Kaleida Health Infusion Center, Department of Medicine, Division of Hematology and Oncology, University at Buffalo, Buffalo, NY 14221, USA
6
City of Hope National Cancer Center, Duarte, CA 91010, USA
7
Department of Medicine, Division of Hematology and Oncology, University at Buffalo, Buffalo, NY 14203, USA
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(16), 2657; https://doi.org/10.3390/cancers17162657
Submission received: 30 June 2025 / Revised: 8 August 2025 / Accepted: 11 August 2025 / Published: 14 August 2025
(This article belongs to the Special Issue Cancer-Therapy-Related Adverse Events (2nd Edition))

Simple Summary

Oral mucositis (OM) is a frequent, debilitating side effect of hematopoietic stem cell transplantation (HSCT), significantly impacting patient outcomes and quality of life. This systematic review and meta-analysis attempted to establish risk factors for OM and its association with infectious complications in recipients of HSCT. Thirty-four studies were conducted, and high-intensity conditioning, administration of methotrexate, female sex, longer neutropenia/neutrophil engraftment, reactivation of HSV-1 infection, and renal impairment appeared as significant risk factors for OM. This meta-analysis demonstrated that patients suffering from OM had nearly four times the risk of developing infections compared with non-OM patients. These findings indicate the importance of early OM diagnosis and OM-prevention strategies in restricting severe complications in immunocompromised patients receiving HSCT.

Abstract

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.
Keywords: oral mucositis; hemopoietic stem cell transplants; risk factors; outcomes; systematic reviews; meta-analysis oral mucositis; hemopoietic stem cell transplants; risk factors; outcomes; systematic reviews; meta-analysis

Share and Cite

MDPI and ACS Style

Eichhorn, S.; Rudin, L.; Ramasamy, C.; Varsani, R.; Padhi, P.; Nassour, N.; Meleveedu, K.; Epstein, J.B.; Semegran, B.; Pili, R.; et al. 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. Cancers 2025, 17, 2657. https://doi.org/10.3390/cancers17162657

AMA Style

Eichhorn S, Rudin L, Ramasamy C, Varsani R, Padhi P, Nassour N, Meleveedu K, Epstein JB, Semegran B, Pili R, et al. 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. Cancers. 2025; 17(16):2657. https://doi.org/10.3390/cancers17162657

Chicago/Turabian Style

Eichhorn, Susan, Lauryn Rudin, Chidambaram Ramasamy, Ridham Varsani, Parikshit Padhi, Nour Nassour, Kapil Meleveedu, Joel B. Epstein, Benjamin Semegran, Roberto Pili, and et al. 2025. "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" Cancers 17, no. 16: 2657. https://doi.org/10.3390/cancers17162657

APA Style

Eichhorn, S., Rudin, L., Ramasamy, C., Varsani, R., Padhi, P., Nassour, N., Meleveedu, K., Epstein, J. B., Semegran, B., Pili, R., & Satheeshkumar, P. S. (2025). 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. Cancers, 17(16), 2657. https://doi.org/10.3390/cancers17162657

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