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Prospective longitudinal analysis of clinical and immunological risk factors associated with oral and gastrointestinal mucositis following autologous stem cell transplant in adults

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Abstract

Purpose

The study aimed to characterize the incidence of both oral and gastrointestinal (GI) mucositis, its’ associated temporal changes in local and systemic pro-inflammatory cytokines, and to explore predictive clinical and immunological factors associated with their occurrences in hematopoietic stem cell transplant (HSCT).

Methods

Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood and saliva were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month. Baseline and inflammatory predictors in a repeated time measurement of moderate-severe mucositis were assessed by multiple logistic regression and generalized estimating equations, respectively.

Results

Of the 142 patients analyzed, oral mucositis and diarrhea (representing GI mucositis) were reported as 68.3% and 95.8%, respectively. Predictive factors for moderate-severe oral mucositis were BEAM or busulphan-based regimens (odds ratio (OR)=9.2, 95% confidence interval (CI)=1.16–72.9, p-value (p) = 0.005) and vomiting (OR=4.6, 95% CI 1.68–12.3, p = 0.004). Predictive factors for moderate-severe GI mucositis were BEAM or busulphan-based regimens (OR=3.9, 95% CI 1.05–14.5, p = 0.023), female sex (OR = 3.3, 95% CI 1.43–7.44, p = 0.004) and body mass index (OR=1.08, 95% CI 1.02–1.15, p = 0.010). Cytokines analyses were performed in 96 patients. Saliva and plasma interleukin-6 (OR=1.003, 95% CI 1.001–1.004, p < 0.001 and OR=1.01, 95% CI 1.001–1.015, p = 0.029), and plasma tumor necrosis factor-alpha (OR=0.91, 95% CI 0.85–0.99, p = 0.019) were predictive of moderate-severe oral mucositis in a time-dependent model.

Conclusion

This study provides real-world evidence and insights into patient- and treatment-related factors affecting oral and GI mucositis in HSCT.

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Data availability

The data that support the findings of this study are available from the corresponding author on reasonable request. The data are not publicly available due to privacy and ethical restrictions.

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Acknowledgements

The authors would like to thank all the staffs of the Haematology Department, Hospital Ampang and Immunotherapeutics Laboratory, Universiti Malaya for their invaluable contribution towards this project. We would like to thank the Director General of Health Malaysia for his permission to publish this article.

Code availability

Not applicable.

Funding

This work was funded by the Ministry of Health, Malaysia through the Research and Technical Support, [grant number: NMRR-18-2946-44954]; and the Malaysian Society of Haematology [2019-005]. The funders had no role in the study design, data acquisition, analysis, report writing, and/or decision to submit the article for publication.

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Authors and Affiliations

  1. Department of Pharmacy, Ampang Hospital, Ministry of Health, Ampang, Selangor Darul Ehsan, Malaysia

    Shu Ping Wong

  2. Department of Haematology, Ampang Hospital, Ministry of Health, Ampang, Selangor Darul Ehsan, Malaysia

    Sen Mui Tan

  3. Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

    Cheng-Siang Lee & Reena Rajasuriar

  4. Institute for Clinical Research, National Institutes of Health, Ministry of Health, Shah Alam, Selangor Darul Ehsan, Malaysia

    Kian Boon Law

  5. Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

    Yvonne Ai Lian Lim

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Contributions

Study conception and design: All authors; Material preparation and data collection: SPW, CSL; Data analysis and interpretation: KBL, SPW, CSL; Manuscript draft: SPW, SMT, YALL, RR; All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Reena Rajasuriar.

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Ethics approval

The protocol of this study was approved by the Medical Research and Ethics Committee, Ministry of Health Malaysia (approval ID: NMRR-18-2946-44954). All procedures were performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

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Written informed consent was obtained from all individual patients included in this study.

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The authors have no competing interests to declare that are relevant to the content of this article.

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Wong, S.P., Tan, S.M., Lee, CS. et al. Prospective longitudinal analysis of clinical and immunological risk factors associated with oral and gastrointestinal mucositis following autologous stem cell transplant in adults. Support Care Cancer 31, 494 (2023). https://doi.org/10.1007/s00520-023-07947-5

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