Brazilian guideline for oral graft-versus-host disease: Recommendations from the Brazilian Society of Bone Marrow Transplantation
DOI:
https://doi.org/10.46765/2675-374X.2025v7n1e380Keywords:
Graft vs Host Disease, Mouth, Transplantation, Homologous, Saliva, Xerostomia, Therapeutics, Mouth NeoplasmsAbstract
Oral chronic graft-versus-host disease (cGVHD) is a frequent and clinically heterogeneous manifestation after allogeneic hematopoietic cell transplantation (HCT). In addition to lichenoid lesions, erythema, and ulceration, the disease can affect the salivary glands, other tissues, quality of life, and is associated with a risk of oral carcinoma. Then, the objective of this study was to update the Brazilian consensus of the Brazilian Society of Bone Marrow Transplantation (Sociedade Brasileira de Transplante de Medula Óssea—SBTMO) on oral cGVHD (2021). A narrative review was conducted including publications from 2021 onward. Evidence and strength of recommendation was graded according to the 2009 Oxford Center for Evidence- Based Medicine. The final recommendations were defined by a panel of SBTMO experts in cGVHD. The most directly applicable evidence supports the use of topical corticosteroids for symptomatic mucosal disease. Photobiomodulation, intraoral ultraviolet B phototherapy, barrier agents, and platelet lysate are promising local options, but supported mainly by small, uncontrolled studies. Ruxolitinib and belumosudil show signals of oral response in patients with refractory disease, but mouthspecific evidence remains observational, secondary or organ-specific, or partially extrapolated; both should be considered conditional second-line or salvage systemic options. Prolonged oral surveillance is necessary due to the risk of secondary oral cancer and other complications. This Brazilian consensus update supports a multidimensional assessment of oral cGVHD and favors local therapy for localized disease whenever feasible. Systemic therapies should be reserved for selected refractory or multiorgan cases, while prevention of oral complications and long-term surveillance remain integral to care.
References
1. Elad S, Aljitawi O, Zadik Y. Oral graft-versus-host disease: a pictorial review and a guide for dental practitioners. Int Dent J. 2021;71(1):9-20. https://doi.org/10.1111/idj.12584
2. Al Masri B, Perry LM, Stoopler ET. Palatal superficial mucoceles associated with chronic graft-versus-host disease. Hematol Transfus Cell Ther. 2023;45(1):140. https://doi.org/10.1016/j.htct.2021.09.014
3. Tollemar V, Legert KG, Sugars RV. Perspectives on oral chronic graft-versus-host disease from immunobiology to morbid diagnoses. Front Immunol. 2023;14:1151493. https://doi.org/10.3389/fimmu.2023.1151493
4. Dean D, Sroussi H. Oral chronic graft-versus-host disease. Front Oral Health. 2022;3:903154. https://doi.org/10.3389/froh.2022.903154
5. Scaraficci AC, Fernandes PM, Alves FA, Schmidt Filho J, Jaguar GC. Oral manifestations of graftversus- host disease in patients submitted to allogeneic hematopoietic stem cell transplantation: the experience of a Brazilian Cancer Center. Support Care Cancer. 2022;30:567-73. https://doi.org/10.1007/s00520-021-06349-9
6. Kambara Y, Fujiwara H, Yamamoto A, Gotoh K, Tsuji S, Kunihiro M, Oyama T, Terao T, Sato A, Tanaka T, Peltier D, Seike K, Nishimori H, Asada N, Ennishi D, Fujii K, Fujii N, Matsuoka KI, Soga Y, Reddy P, Maeda Y. Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease. Blood. 2025;145(8):881-96. https://doi.org/10.1182/blood.2024024540
7. Yamamoto A, Kambara Y, Fujiwara H. Impact of oral microbiota on pathophysiology of GVHD. Front Immunol. 2023;14:1132983. https://doi.org/10.3389/fimmu.2023.1132983
8. Correa MEP, Eduardo FP, Macedo LD, Bezinelli LM, Santos PSS, Antunes HS. Oral graft-versus-host diseases. J Bone Marrow Transplant Cell Ther. 2021;2(1):181-6. https://doi.org/10.46765/2675-374X. 2021v4n1p181-186
9. Oxford Centre for Evidence-Based Medicine. Levels of Evidence [Internet]. Oxford: Centre for Evidence-Based Medicine, University of Oxford; 2009 [cited 2026 Aug 16]. Available from: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidencemarch-2009
10. Nguyen JT, Jessri M, Costa-da-Silva AC, Sharma R, Mays JW, Treister NS. Oral chronic graft-versus-host disease: pathogenesis, diagnosis, current treatment, and emerging therapies. Int J Mol Sci. 2024; 25 (19): 10411. https://doi.org/10.3390/ijms251910411
11. Bassim CW, Fassil H, Mays JW, Edwards D, Baird K, Steinberg SM, Williams KM, Cowen EW, Mitchell SA, Cole K, Taylor T, Avila D, Zhang D, Pulanic D, Grkovic L, Fowler D, Gress RE, Pavletic SZ. Validation of the National Institutes of Health chronic GVHD Oral Mucosal Score using component-specific measures. Bone Marrow Transplant. 2014;49(1):116-21. https://doi.org/10.1038/bmt.2013.137
12. Treister N, Chai X, Kurland B, Pavletic S, Weisdorf D, Pidala J, Palmer J, Martin P, Inamoto Y, Arora M, Flowers M, Jacobsohn D, Jagasia M, Arai S, Lee SJ, Cutler C. Measurement of oral chronic GVHD: results from the Chronic GVHD Consortium. Bone Marrow Transplant. 2013;48(8):1123-8. https://doi.org/10.1038/bmt.2012.285
13. Stolze J, Boor M, Hazenberg MD, Brand HS, Raber-Durlacher JE, Laheij AMGA. Oral health–related quality of life of patients with oral chronic graft-versus-host disease. Support Care Cancer. 2021;29:6353-60. https://doi.org/10.1007/s00520-021-06197-7
14. DePalo J, Chai X, Lee SJ, Cutler CS, Treister N. Assessing the relationship between oral chronic graft-versus-host disease and global measures of quality of life. Oral Oncol. 2015;51(10):944-9. https://doi.org/10.1016/j.oraloncology.2015.07.009
15. Tollemar V, Arvidsson H, Häbel H, Tudzarovski N, Legert KG, Le Blanc K, Warfvinge G, Sugars RV. Grading of minor salivary gland immuno-histopathology post-allogenic hematopoietic cell transplantation. Heliyon. 2023;9(4):e15517. https://doi.org/10.1016/j.heliyon.2023.e15517
16. Sato S, Shimizu E, He J, Ogawa M, Asai K, Yazu H, Rusch R, Yamane M, Yang F, Fukuda S, Kawakami Y, Tsubota K, Ogawa Y. Positive effects of oral antibiotic administration in murine chronic graft-versus-host disease. Int J Mol Sci. 2021;22(7):3745. https://doi.org/10.3390/ijms22073745
17. Haas L, Cruz-Pamplona M. Topical treatment of oral chronic graft-versus-host-disease in hematopoietic stem cell transplant recipients: A systematic review. J Clin Exp Dent. 2023;15(5):e420-7. https://doi.org/10.4317/jced.60138
18. Noce CW, Gomes A, Shcaira V, Corrêa MEP, Moreira MCR, Silva Júnior A, Gonçalves LS, Garnica M, Maiolino A, Torres SR. Randomized double-blind clinical trial comparing clobetasol and dexamethasone for the topical treatment of symptomatic oral chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20(8):1163-8. https://doi.org/10.1016/j.bbmt.2014.04.009
19. Treister N, Li S, Kim H, Lerman M, Sultan A, Alyea EP, Armand P, Cutler C, Ho V, Koreth J, Antin JH, Soiffer R. An open-label phase II randomized trial of topical dexamethasone and tacrolimus solutions for the treatment of oral chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2016;22(11):2084-91. https://doi.org/10.1016/j.bbmt.2016.08.020
20. Elad S, Zeevi I, Finke J, Koldehoff M, Schwerdtfeger R, Wolff D, Mohrbacher R, Levitt M, Greinwald R, Shapira MY. Improvement in oral chronic graft-versus-host disease with the administration of effervescent tablets of topical budesonide-an open, randomized, multicenter study. Biol Blood Marrow Transplant. 2012;18(1):134-40. https://doi.org/10.1016/j.bbmt.2011.06.001
21. Epstein JB, Raber-Durlacher JE, Epstein GL, Hazenberg MD, Tzachanis D, Spielberger RT. Chronic oral graft-versus-host disease: induction and maintenance therapy with photobiomodulation therapy. Support Care Cancer. 2021;29:1387-94. https://doi.org/10.1007/s00520-020-05626-3
22. Finfter O, Avni B, Grisariu S, Haviv Y, Nadler C, Rimon O, Zadik Y. Photobiomodulation (low-level laser) therapy for immediate pain relief of persistent oral ulcers in chronic graft-versus-host disease. Support Care Cancer. 2021;29:4529-34. https://doi.org/10.1007/s00520-021-05997-1
23. Choi E, Lenga M, Nguyen CV, Zheng L, Froelich A, Centanni E, Choi JN. Treatment of oral graft-versus-host disease with intraoral nbUVB phototherapy. Support Care Cancer. 2024;32:438. https://doi.org/10.1007/s00520-024-08642-9
24. Cao J, Ye L, Li X, Song Q, Chai Y. Early intervention with oral mucosal barrier protective agents in chronic oral graft-versus-host disease: a retrospective cohort study. BMC Oral Health. 2024;24:958. https://doi.org/10.1186/s12903-024-04724-6
36. Mousavian M, Sroussi H, Villa A, Cutler C, Treister N. Use of prescription sialagogues for management of xerostomia in chronic graft-versus-host-disease. Transplant Cell Ther. 2021; 27(6): 480. e1-e5. https://doi.org/10.1016/j.jtct.2021.02.020
37. Calarga CC, Brito CBT, Cotomácio CC, Simões A. Photobiomodulation for salivary gland dysfunction: aligning clinical expectations with etiology-dependent treatment responsiveness. Lasers Med Sci. 2026; 41:196. https://doi.org/10.1007/s10103-026-04991-5
38. Treister NS, Liang L, Lee SJ, Cutler C, Gooley TA, Hujoel P, Gbujie D, Oh UY, Bennett-Johnson L, Hagstrom MK, Rothen M, Lloid M, Dean D, Sroussi H. Tooth loss and oral health-related quality of life in a sub-cohort within the Chronic Graft-Versus-Host Disease Consortium. Transplant Cell Ther. 2026; 32(7): 893.e1-e10. https://doi.org/10.1016/j.jtct.2026.03.004
39. Johnson LB, Oh U, Rothen M, Sroussi HY, Dean DR, Lloid CM, Cintron K, Lee SJ, Cutler CS, Treister NS. A review of oral chronic graft-versus-host disease: considerations for dental hygiene practice. J Dent Hyg. 2022; 96 (2): 6-17. https://jdh.adha.org/content/96/2/6
40. Correa MEP, Granzotto FCN, Innocentini LMAR, Reis TC, Lima EM, Varanda RF, Santos PSS, Soares Junior LAV, Bezinelli LM, Eduardo FP, Melo WR, Antunes HS, Macedo LD. Brazilian dental consensus on dental management in hematopoietic stem cell transplantation - Part I - pre-HCT. Hematol Transfus Cell Ther. 2023;45(3):358-67. https://doi.org/10.1016/j.htct.2023.04.001
41. Gobbi MF, Ferreira MH, Carvalho DLC, Silva GBL, Macari KSM, Neves LJ, Santos PSS, Soares Junior LAV, Melo WR, Antunes HS, Macedo LD, Eduardo FP, Bezinelli LM. Dental consensus on HCT - Part II: dental care during HCT. Hematol Transfus Cell Ther. 2023;45(3):368-78. https://doi.org/10.1016/j.htct.2023.04.003
42. Santos PSS, Granzotto FCN, Antunes HS, de Lima EM, Varanda RF, Maccari K, Bezinelli LM, Melo WR, Soares Junior LAV, Macedo LD, Eduardo FP. Dentistry consensus on HCT - Part III: special topics - dentistry on HCT. Hematol Transfus Cell Ther. 2023;45(3):379-86. https://doi.org/10.1016/j.htct.2023.04.004
43. Boor M, Raber-Durlacher JE, Hazenberg MD, Rozema FR, Laheij AMGA. Taste and smell disturbances in patients with chronic oral graft vs. host disease: An observational study. Front Oral Health. 2022; 3: 934607. https://doi.org/10.3389/froh.2022.934607
44. Treister N, Duncan C, Cutler C, Lehmann L. How we treat oral chronic graft-versus-host disease. Blood. 2012;120(17):3407-18. https://doi.org/10.1182/blood-2012-05-393389
45. Zadik Y, Raber-Durlacher JE, Epstein JB, Majorana A, Laheij A, Bardellini E, Blijlevens N, Elad S. MASCC/ISOO Clinical Practice Statement: Management of oral manifestations of chronic graft-versus-host-disease. Support Care Cancer. 2024;32:546. https://doi.org/10.1007/s00520-024-08686-x
46. Laheij AMGA, Fregnani ER, Macedo LD, Treister NS. Oral chronic graft-versus-host disease and oral health after allogeneic hematopoietic cell transplantation—what the care team needs to know. Transplant Cell Ther. 2024;30(9 Suppl.):S548-58. https://doi.org/10.1016/j.jtct.2024.07.006
47. Haverman TM, Raber-Durlacher JE, Raghoebar II, Rademacher WMH, Rozema FR, Hazenberg MD, Epstein JB, Treister NS. Oral chronic graft-versus-host disease: What the general dental practitioner needs to know. J Am Dent Assoc. 2020;151(11):846-56. https://doi.org/10.1016/j.adaj.2020.08.001
48. Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons’ position paper on medication-related osteonecrosis of the jaws-2022 update. J Oral Maxillofac Surg. 2022;80(5):920-43. https://doi.org/10.1016/j.joms.2022.02.008
49. Gervazio TC, Silva JK, Evangelista K, Cavalcanti MGP, Silva MAGSS, Yamamoto-Silva FP, Silva BSF. Risk of oral cancer in patients with graft-vs-host disease: A systematic review and meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2022;133(6):650-62. https://doi.org/10.1016/j.oooo.2022.02.002
50. Santarone S, Natale A, Angelini S, Papalinetti G, Vaddinelli D, Di Bartolomeo A, Di Bartolomeo P. Secondary oral cancer following hematopoietic cell transplantation. Bone Marrow Transplant. 2021;56:1038-46. https://doi.org/10.1038/s41409-020-01147-z
51. Janowiak-Majeranowska A, Osowski J, Mikaszewski B, Majeranowski A. Secondary oral cancer after systemic treatment of hematological malignancies and oral GVHD: a systematic review. Cancers. 2022;14(9):2175. https://doi.org/10.3390/cancers14092175
52. Cantile T, Coppola N, Canfora F, Adamo D, Ruoppo E, Mignogna MD, Leuci S. Oral cancer in HCT pediatric patients arising on GVHD: a comprehensive review. Cancers. 2022;14(23):5775. https://doi.org/10.3390/cancers14235775
53. Fanconi Anemia Research Fund. Head and neck cancer in patients with Fanconi anemia. Clinical Care Guidelines [Internet]. Fanconi Anemia Research Fund [cited 2026 Aug 16]. Available at: https://fanconi.org/clinical-care-guidelines/head-and-neck-cancer-in-patients-with-fanconi-anemia/
54. Raber-Durlacher JE, Treister NS, Zadik Y, Dean DR, Miranda-Silva W, Fregnani ER, Epstein JB, Elad S.
MASCC/ISOO Clinical Practice Statement: The risk of secondary oral cancer following hematopoietic cell transplantation. Support Care Cancer. 2024;32:545. https://doi.org/10.1007/s00520-024-08685-y
55. Navazesh M, Kumar SK. Measuring salivary flow: challenges and opportunities. J Am Dent Assoc. 2008; 139 (Suppl. 2):35S-40S. https://doi.org/10.14219/jada.archive.2008.0353
56. Fontana M, Zunt S, Eckert GJ, Zero D. A screening test for unstimulated salivary flow measurement. Oper Dent. 2005;30(1):3-8. https://operative-dentistry.kglmeridian.com/downloadpdf/view/journals/odnt/30/1/article-p1.pdf
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Copyright (c) 2026 Leandro Dorigan de Macedo, Mariana Andrade Costa, Fernanda de Paula Eduardo, Leticia Mello Bezinelli, Paulo Sergio da Silva Santos, Heliton Spíndola Antunes, Maria Elvira Pizzigatti Correa
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