Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 Jul 17;32(8):519.
doi: 10.1007/s00520-024-08722-w.

Comparing the risk of severe oral mucositis associated with methotrexate as graft-versus host-disease prophylaxis to other immunosuppressive prophylactic agents in hematopoietic cell transplantation: a systematic review and meta-analysis

Aisha A H Al-Jamaei  1   2   3 , Joel B Epstein  4   5 , Jan G A M de Visscher  1 , Ricardo T Spielberger  6   7 , Ryotaro Nakamura  7 , Judith E Raber-Durlacher  8   9
Affiliations
Meta-Analysis

Comparing the risk of severe oral mucositis associated with methotrexate as graft-versus host-disease prophylaxis to other immunosuppressive prophylactic agents in hematopoietic cell transplantation: a systematic review and meta-analysis

Aisha A H Al-Jamaei et al. Support Care Cancer. .

Abstract

Purpose: This study examines the risk of severe oral mucositis (SOM) in graft-versus-host disease prophylaxis (GVHD) compared to other agents in hematopoietic cell transplantation patients.

Methods: A comprehensive search of four databases, including PubMed, Embassy, Web of Science, and Scopus, was conducted to identify studies reporting frequency and severity of oral mucositis in association with GVHD prophylactic regimens. RevMan 5.4 was used to perform the meta-analysis. Risk of bias assessment was carried out using the Rob-2 tool for randomized clinical trials (RCTs) and ROBINS-I tool for observational studies.

Results: Twenty-five papers, including 11 RCTs and 14 observational studies, met the inclusion criteria. The pooled results from eight RCTs showed a higher risk of SOM in patients receiving MTX or MTX-inclusive GVHD prophylaxis versus non-MTX alternatives (RR = 1.50, 95% CI [1.20, 1.87], I2 = 36%, P = 0.0003). Mycophenolate mofetil (MMF) and post-transplant cyclophosphamide (Pt-Cy) consistently showed lower risk of mucositis than MTX. Folinic acid (FA) rescue and mini-dosing of MTX were associated with reduced oral mucositis severity.

Conclusion: Patients receiving MTX have a higher SOM risk compared to other approaches to prevent GVHD, which should be considered in patient care. When appropriate, MMF, FA, and a mini-dose of MTX may be an alternative that is associated with less SOM. This work also underlines the scarcity of RCTs on MTX interventions to provide the best evidence-based recommendations.

Keywords: Graft versus host disease; HCT; Hematopoietic cell transplantation; Methotrexate; Oral mucositis.

PubMed Disclaimer

Conflict of interest statement

A.H. Al-Jamaei, Joel B. Epstein, Jan G.A.M. de Visscher, Ricardo T. Spielberger, Ryotaro Nakamura, and Judith E. Raber-Durlacher reported no relevant financial or non-financial interests to disclose within the last 3 years of beginning the work and none outside the 3-year time frame that could reasonably be perceived as influencing the submitted work. J.B. Epstein is associated Editor-in-Chief for Supportive Care in Cancer.

Figures

Fig. 1
Fig. 1
Flow chart depicting the selection process of the included studies. Reviews and preclinical studies as well as clinical studies that provided no outcome of interest were excluded
Fig. 2
Fig. 2
Forest plot of RCTs comparing risk of SOM in association with MTX vs. all comparators
Fig. 3
Fig. 3
Forest plot of RCTs comparing risk of SOM in association with MTX vs. CsA
Fig. 4
Fig. 4
A Forest plot of RCTs comparing risk of SOM in association with MTX vs. MMF. B Forest plot of observational studies comparing risk of SOM in association with MTX vs. MMF
Fig. 5
Fig. 5
A Forest plot of RCTs comparing risk of SOM in association with MTX/FA vs. MTX without FA. B Forest plot of observational studies comparing risk of SOM in association with MTX/FA vs. MTX without FA
Fig. 6
Fig. 6
Forest plot of observational studies comparing risk of SOM in association with MTX vs. Pt-cy
Fig. 7
Fig. 7
A) Risk of bias summary. B) Risk of bias graph
See this image and copyright information in PMC

References

    1. Duarte RF, Labopin M, Bader P, Basak GW, Bonini C, Chabannon C et al (2019) Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transpl 54(10):1525–52. 10.1038/s41409-019-0516-2 10.1038/s41409-019-0516-2 - DOI - PubMed
    1. Khaddour K, Hana CK, Mewawalla P (2023) Hematopoietic Stem Cell Transplantation. In: StatPearls. StatPearls Publishing, Treasure Island (FL) - PubMed
    1. Godder KT, Henslee-Downey PJ, Mehta J, Park BS, Chiang KY, Abhyankar S, Lamb LS (2007) Long term disease-free survival in acute leukemia patients recovering with increased γδ T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transpl 39(12):751–7. 10.1038/sj.bmt.1705650 10.1038/sj.bmt.1705650 - DOI - PubMed
    1. Østgård LSG, Lund JL, Nørgaard JM, Nørgaard M, Medeiros BC, Nielsen B et al (2018) Impact of allogeneic stem cell transplantation in first complete remission in acute myeloid leukemia: a national population-based cohort study. Biol Blood Marrow Transplant 24:314-23. 10.1016/j.bbmt.2017.10.019. - PubMed
    1. Gyurkocza B, Sandmaier BM (2014) Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood 124:344–53. 10.1182/blood-2014-02-514778 10.1182/blood-2014-02-514778 - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources