Skip to main content

Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers

Supportive Care in Cancer volume 23, pages 1615–1622 (2015)Cite this article

Abstract

Background

The oral cavity is frequently affected in chronic graft-versus-host disease (cGVHD), with variable clinical presentations. The literature on the effective management of patients suffering from oral cGVHD is limited.

Objective

The objective of this study was to assess the clinical approaches used in the diagnosis and treatment of cGVHD in a group of health-care providers specialized in the oral care of oncology patients. The secondary objective was to assess the level of implementation of the National Institutes of Health (NIH) guidelines for cGVHD patients.

Methods

One hundred twenty questionnaires were sent to the members of the Oral Care Study Group (OCSG) of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The questionnaire included 50 questions about the responder’s demographics, level of exposure to cGVHD patients, diagnostic and evaluation methods in their practice, preferred treatment strategies for mucosal and salivary gland involvement, and preventive measures.

Results

Twelve responders, representing 12 sites, stated that they treat oral cGVHD patients on a regular basis. This fraction of responders was confirmed by another online survey. Eleven out of the 12 providers were dentists. Seventy-five percent of the providers did not use biopsy in order to diagnose oral cGVHD. The NIH scale for the clinical assessment was used sporadically. The first-line topical treatment for oral mucosal cGVHD was predominantly steroids (91.7 %), and the second preferred treatment was tacrolimus (41.7 %). The preferred treatment for hyposalivation was pilocarpine (41.7 %). The recommended frequency of oral cancer screening varied; half of the providers suggest a follow-up every 6 months.

Conclusions

The responses described the common practices for oral cGVHD in several specialized centers across the world. The choice of topical treatments was influenced by the availability of medications in the provider’s country.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. Socie G, Ritz J (2014) Current issues in chronic graft-versus-host disease. Blood 124(3):374–384

    Article  CAS  PubMed  Google Scholar 

  2. Blazar BR, Murphy WJ, Abedi M (2012) Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol 12(6):443–458

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 11(12):945–956

    Article  PubMed  Google Scholar 

  4. Schubert MM, Correa ME (2008) Oral graft-versus-host disease. Dent Clin North Am 52(1):79–109, viii-ix

    Article  PubMed  Google Scholar 

  5. Kuten-Shorrer M, Woo SB, Treister NS (2014) Oral graft-versus-host disease. Dent Clin North Am 58(2):351–368

    Article  PubMed  Google Scholar 

  6. Daikeler T, Mauramo M, Rovo A, Stern M, Halter J, Buser A et al (2013) Sicca symptoms and their impact on quality of life among very long-term survivors after hematopoietic SCT. Bone Marrow Transplant 48(7):988–993

    Article  CAS  PubMed  Google Scholar 

  7. Treister NS, Cook EF Jr, Antin J, Lee SJ, Soiffer R, Woo SB (2008) Clinical evaluation of oral chronic graft-versus-host disease. Biol Blood Marrow Transplant 14(1):110–115

    Article  PubMed  Google Scholar 

  8. Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW et al (2006) Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. Response criteria working group report. Biol Blood Marrow Transplant 12(3):252–266

    Article  PubMed  Google Scholar 

  9. Schubert MM, Sullivan KM (1990) Recognition, incidence, and management of oral graft-versus-host disease. NCI Monogr 9:135–143

    PubMed  Google Scholar 

  10. Garcia FVMJ, Pascual-Lopez M, Elices M, Dauden E, Garcia-Diez A, Fraga J (2002) Superficial mucoceles and lichenoid graft versus host disease: report of three cases. Acta Derm Venereol 82(6):453–455

    Article  Google Scholar 

  11. Mays JW, Fassil H, Edwards DA, Pavletic SZ, Bassim CW (2013) Oral chronic graft-versus-host disease: current pathogenesis, therapy, and research. Oral Dis 19(4):327–346

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Couriel D, Carpenter PA, Cutler C, Bolanos-Meade J, Treister NS, Gea-Banacloche J et al (2006) Ancillary therapy and supportive care of chronic graft-versus-host disease: national institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: V. Ancillary therapy and supportive care working group report. Biol Blood Marrow Transplant 12(4):375–396

    Article  PubMed  Google Scholar 

  13. Mawardi H, Elad S, Correa ME, Stevenson K, Woo SB, Almazrooa S et al (2011) Oral epithelial dysplasia and squamous cell carcinoma following allogeneic hematopoietic stem cell transplantation: clinical presentation and treatment outcomes. Bone Marrow Transplant 46(6):884–891

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Treister N, Duncan C, Cutler C, Lehmann L (2012) How we treat oral chronic graft-versus-host disease. Blood 120(17):3407–3418

    Article  CAS  PubMed  Google Scholar 

  15. Majhail NS, Rizzo JD, Lee SJ, Aljurf M, Atsuta Y, Bonfim C et al (2012) Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Bone Marrow Transplant 47(3):337–341

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Schubert MM, Williams BE, Lloid ME, Donaldson G, Chapko MK (1992) Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation. Development of an oral mucositis index. Cancer 69(10):2469–2477

    Article  CAS  PubMed  Google Scholar 

  17. Meier JK, Wolff D, Pavletic S, Greinix H, Gosau M, Bertz H et al (2011) Oral chronic graft-versus-host disease: report from the International Consensus Conference on clinical practice in cGVHD. Clin Oral Investig 15(2):127–139

    Article  PubMed  Google Scholar 

  18. Dignan FL, Scarisbrick JJ, Cornish J, Clark A, Amrolia P, Jackson G et al (2012) Organ-specific management and supportive care in chronic graft-versus-host disease. Br J Haematol 158(1):62–78

    Article  CAS  PubMed  Google Scholar 

  19. McCormack HM, Horne DJ, Sheather S (1988) Clinical applications of visual analogue scales: a critical review. Psychol Med 18(4):1007–1019

    Article  CAS  PubMed  Google Scholar 

  20. Elad S, Zeevi I, Finke J, Koldehoff M, Schwerdtfeger R, Wolff D et al (2012) 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 18(1):134–140

    Article  CAS  PubMed  Google Scholar 

  21. Park AR, La HO, Cho BS, Kim SJ, Lee BK, Rhie JY et al (2013) Comparison of budesonide and dexamethasone for local treatment of oral chronic graft-versus-host disease. Am J Health Syst Pharm 70(16):1383–1391

    Article  PubMed  Google Scholar 

  22. Noce CW, Gomes A, Shcaira V, Correa ME, Moreira MC, Silva Junior A et al (2014) 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 20(8):1163–1168

    Article  CAS  PubMed  Google Scholar 

  23. Sari I, Altuntas F, Kocyigit I, Sisman Y, Eser B, Unal A et al (2007) The effect of budesonide mouthwash on oral chronic graft versus host disease. Am J Hematol 82(5):349–356

    Article  CAS  PubMed  Google Scholar 

  24. Fortune K, Couriel D (2009) Tacrolimus in hematopoietic stem cell transplantation. Expert Opin Drug Metab Toxicol 5(7):835–841

    Article  CAS  PubMed  Google Scholar 

  25. Mawardi H, Stevenson K, Gokani B, Soiffer R, Treister N (2010) Combined topical dexamethasone/tacrolimus therapy for management of oral chronic GVHD. Bone Marrow Transplant 45(6):1062–1067

    Article  CAS  PubMed  Google Scholar 

  26. Brown RS, Edwards D, Walsh-Chocolaad T, Childs RW (2013) Topical tacrolimus with custom trays in the treatment of severe oral chronic graft-versus-host disease refractory to a potent topical steroid therapy: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol 115(4):e26–e30

    Article  PubMed Central  PubMed  Google Scholar 

  27. Eckardt A, Starke O, Stadler M, Reuter C, Hertenstein B (2004) Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus. Oral Oncol 40(8):811–814

    Article  PubMed  Google Scholar 

  28. Fricain JC, Sibaud V, Swetyenga N, Tabrizi R, Campana F, Taieb A (2007) Long-term efficacy of topical tacrolimus on oral lesions of chronic graft-versus-host disease. Br J Dermatol 156(3):588–590

    Article  CAS  PubMed  Google Scholar 

  29. Conrotto D, Broccoletti R, Carcieri P, Giaccone L, Arduino PG (2014) Topical tacrolimus and periodontal therapy in the management of a case of oral chronic GVHD characterized by specific gingival localization. Case Rep Dent 2014:127219

    PubMed Central  PubMed  Google Scholar 

  30. Elad S, Or R, Shapira MY, Haviv A, Galili D, Garfunkel AA et al (2003) CO2 laser in oral graft-versus-host disease: a pilot study. Bone Marrow Transplant 32(10):1031–1034

    Article  CAS  PubMed  Google Scholar 

  31. Nozaki-Taguchi N, Shutoh M, Shimoyama N (2008) Potential utility of peripherally applied loperamide in oral chronic graft-versus-host disease related pain. Jpn J Clin Oncol 38(12):857–860

    Article  PubMed  Google Scholar 

  32. Singhal S, Powles R, Treleaven J, Rattenbury H, Mehta J (1997) Pilocarpine hydrochloride for symptomatic relief of xerostomia due to chronic graft-versus-host disease or total-body irradiation after bone-marrow transplantation for hematologic malignancies. Leuk Lymphoma 24(5–6):539–543

    Article  CAS  PubMed  Google Scholar 

  33. Nagler RM, Nagler A (1999) Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease: a sialometrical study. Bone Marrow Transplant 23(10):1007–1011

    Article  CAS  PubMed  Google Scholar 

  34. Agha-Hosseini F, Mirzaii-Dizgah I, Ghavamzadeh L, Ghavamzadeh A, Tohidast-Acrad Z (2007) Effect of pilocarpine hydrochloride on unstimulated whole saliva flow rate and composition in patients with chronic graft-versus-host disease (cGVHD). Bone Marrow Transplant 39(7):431–434

    Article  CAS  PubMed  Google Scholar 

  35. Carpenter PA, Schubert MM, Flowers ME (2006) Cevimeline reduced mouth dryness and increased salivary flow in patients with xerostomia complicating chronic graft-versus-host disease. Biol Blood Marrow Transplant 12(7):792–794

    Article  PubMed  Google Scholar 

  36. Castellarin P, Stevenson K, Biasotto M, Yuan A, Woo SB, Treister NS (2012) Extensive dental caries in patients with oral chronic graft-versus-host disease. Biol Blood Marrow Transplant 18(10):1573–1579

    Article  PubMed  Google Scholar 

  37. Epstein JB, Gorsky M, Fischer D, Gupta A, Epstein M, Elad S (2007) A survey of the current approaches to diagnosis and management of oral premalignant lesions. J Am Dent Assoc 138(12):1555–1562, quiz 614

    Article  PubMed  Google Scholar 

  38. Atsuta Y, Suzuki R, Yamashita T, Fukuda T, Miyamura K, Taniguchi S et al (2014) Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease. Ann Oncol 25(2):435–441

    Article  CAS  PubMed  Google Scholar 

  39. Majhail NS, Brazauskas R, Rizzo JD, Sobecks RM, Wang Z, Horowitz MM et al (2011) Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood 117(1):316–322

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Kruse AL, Gratz KW (2009) Oral carcinoma after hematopoietic stem cell transplantation—a new classification based on a literature review over 30 years. Head Neck Oncol 1:29

    Article  PubMed Central  PubMed  Google Scholar 

  41. Elad S, Zadik Y, Zeevi I, Miyazaki A, de Figueiredo MA, Or R (2010) Oral cancer in patients after hematopoietic stem-cell transplantation: long-term follow-up suggests an increased risk for recurrence. Transplantation 90(11):1243–1244

    Article  PubMed  Google Scholar 

  42. Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socie G, Travis LB et al (1997) Solid cancers after bone marrow transplantation. N Engl J Med 336(13):897–904

    Article  CAS  PubMed  Google Scholar 

  43. Elad S, Zeevi I, Or R, Resnick IB, Dray L, Shapira MY (2010) Validation of the National Institutes of Health (NIH) scale for oral chronic graft-versus-host disease (cGVHD). Biol Blood Marrow Transplant 16(1):62–69

    Article  PubMed  Google Scholar 

  44. Treister NS, Stevenson K, Kim H, Woo SB, Soiffer R, Cutler C (2010) Oral chronic graft-versus-host disease scoring using the NIH consensus criteria. Biol Blood Marrow Transplant 16(1):108–114

    Article  PubMed  Google Scholar 

  45. Bassim CW, Fassil H, Mays JW, Edwards D, Baird K, Steinberg SM et al (2014) Validation of the National Institutes of Health chronic GVHD Oral Mucosal Score using component-specific measures. Bone Marrow Transplant 49(1):116–121

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Oral Care Study Group of the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) for supporting this project.

Conflict of interest

The following authors disclosed their relationship to the BUM-5 study sponsored by Dr. Falk Pharma Ltd.: S. Elad is the medical expert, J.B. Epstein is an investigator, and Y. Zadik is an investigator (no financial relationship with the sponsor). All other co-authors have no conflict of interest to disclose.

The corresponding author has full control of all primary data and agrees to allow the journal to review these data if requested.

Author information

Authors and Affiliations

  1. Division of Oral Medicine, Eastman Institute for Oral Health, University of Rochester Medical Center, 625 Elmwood Ave., Rochester, NY, 14620, USA

    Sharon Elad

  2. Wilmot Cancer Center, Strong Memorial Hospital, University of Rochester Medical Center, Rochester, NY, USA

    Sharon Elad

  3. Section of Oral Medicine, Clinical Oral Physiology, Oral Pathology and Anatomy, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Siri Beier Jensen

  4. Department of Oral and Maxillofacial Surgery, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands

    Judith E. Raber-Durlacher

  5. Department of Periodontology and Department of Medical Dental Interaction, Academic Centre for Dentistry Amsterdam, Amsterdam, The Netherlands

    Judith E. Raber-Durlacher

  6. Division of Periodontology, Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA

    Nancy Mouradian

  7. Oral Medicine; Dental Ambulatory of the Hematology and Hemotherapy Center, Department of Oral Pathology, Piracicaba Dental School, University of Campinas, Campinas, Brazil

    Elvira M. P. Correa

  8. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Mark M. Schubert

  9. School of Dentistry, University of Washington School of Medicine, Seattle, WA, USA

    Mark M. Schubert

  10. Oral Medicine, Seattle Cancer Care Alliance, Seattle, WA, USA

    Mark M. Schubert

  11. Department of Haematology, Radboud University Medical Center, Nijmegen, The Netherlands

    Nicole M. A. Blijlevens

  12. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Joel B. Epstein

  13. City of Hope National Medical Center, Duarte, CA, USA

    Joel B. Epstein

  14. Department of Dental Oncology, Health Sciences North, North East Cancer Center, Sudbury, ON, Canada

    Deborah P. Saunders

  15. Klinik für Präventivzahnmedizin und Orale Mikrobiologie, Universitätskliniken für Zahnmedizin der Universität Basel, Basel, Switzerland

    Tuomas Waltimo

  16. Department of Oral and Maxillofacial Surgery, Sheba Medical Center Tel-Hashomer, Tel-Aviv, Israel

    Noam Yarom

  17. Department of Oral Pathology and Oral Medicine, School of Dental Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Noam Yarom

  18. Israeli Air Force General Surgeon Headquarters, Israel Defense Forces Medical Corps Tel Hashomer, Jerusalem, Israel

    Yehuda Zadik

  19. Department of Oral Medicine, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel

    Yehuda Zadik

  20. Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA

    Michael T. Brennan

Authors
  1. Sharon Elad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siri Beier Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Judith E. Raber-Durlacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nancy Mouradian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elvira M. P. Correa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark M. Schubert
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nicole M. A. Blijlevens
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Joel B. Epstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Deborah P. Saunders
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tuomas Waltimo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Noam Yarom
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yehuda Zadik
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michael T. Brennan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sharon Elad.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Elad, S., Jensen, S.B., Raber-Durlacher, J.E. et al. Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers. Support Care Cancer 23, 1615–1622 (2015). https://doi.org/10.1007/s00520-014-2503-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-014-2503-x

Keywords

  • Oral chronic graft-versus-host disease
  • NIH scale
  • Oral care
  • Topical treatment
  • Oral mucosa
  • Salivary glands
  • Oral cancer