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Oral manifestations of graft-versus-host disease in patients submitted to allogeneic hematopoietic stem cell transplantation: the experience of a Brazilian Cancer Center

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Abstract

Purpose

Graft-versus-host disease (GVHD) is an important complication of allogeneic hematopoietic stem cell transplantation (AHCT) that affects several organs, including the mouth.

Objectives

The aim of the present study was to describe the prevalence and clinical manifestations of oral GVHD, to determine the time interval from AHCT to the onset of oral GVHD manifestations, to identify predictive factors of oral GVHD, and to evaluate the survival rates of patients diagnosed with oral GVHD.

Methods

Medical records of 147 patients who underwent AHCT between January 2010 and January 2015 were reviewed for clinical features and the statistical establishment of risk factors.

Results

Of the 147 patients in the study, 99 (67.3%) developed GVHD. The skin was the most affected site (45.6%), followed by the gastrointestinal tract (27.9%) and oral cavity (17.7%). The mean post-AHCT oral GVHD development time was 229 days. Among patients with oral GVHD, pain was the main complaint (96.2%) followed by xerostomia (65.4%). The most common oral manifestations were ulcers (53.8%) followed by striae-associated ulcers (19.2%), mostly affecting the buccal mucosa and tongue. Seventy-three patients (48.6%) died within 20 months of receiving AHCT. Cox regression analysis indicated that patients who received myeloablative conditioning regimen had higher survival rate than those who underwent a reduced-intensity conditioning regimen (RR = 0.541; 95% CI, 0.334–0.878; p = 0.03).

Conclusion

The mouth was the third most common GVHD-affected site. Pain, xerostomia, and ulcers with or without striae were the main clinical manifestations of GVHD observed in our study cohort. Reduced-intensity conditioning regimen showed significant relationship with mortality risk.

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References

  1. Li HW, Sykes M (2012) Emerging concepts in haematopoietic cell transplantation. Nat Rev Immunol 12(6):403–416

    Article  CAS  Google Scholar 

  2. 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  CAS  Google Scholar 

  3. Zadik Y, Elad S, Shapira A, Shapira MY (2017) Treatment of oral mucosal manifestations of chronic graft-versus-host disease: dexamethasone vs. budesonide. Expert Opin Pharmacother 18(3):235–242

    Article  CAS  Google Scholar 

  4. Piccin A, Tagnin M, Vecchiato C, Al-Khaffaf A, Beqiri L, Kaiser C, AgreiterI Negri G, Kob M, Di Pierro A, Vittadello F, Mazzoleni G, Eisendle K, Fontanella F (2018) Graft-versus-host disease (GvHD) of the tongue and of the oral cavity: a large retrospective study. Int J Hematol 108(6):615–621

    Article  Google Scholar 

  5. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME (2015) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant 21(3):389-401.e1

    Article  Google Scholar 

  6. Nassereddine S, Rafei H, Elbahesh E, Tabbara I (2017) Acute graft versus host disease: a comprehensive review. Anticancer Res 37(4):1547–1555

    Article  CAS  Google Scholar 

  7. Margaix-Muñoz M, Bagán JV, Jiménez Y, Sarrión MG, Poveda-Roda R (2015) Graftversus-host disease affecting oral cavity. A review J Clin Exp Dent 7(1):e138–e145

    Article  Google Scholar 

  8. Bardellini E, Amadori F, Conti G, Veneri F, Majorana A (2019) Effectiveness of a spray containing 1% malic acid in patients with xerostomia induced by graft-versus-host disease. Med Oral Patol Oral Cir Bucal 24(2):e190–e194

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 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 (2014) Validation of the National Institutes of Health chronic GVHD Oral Mucosal Score using component-specific measures. Bone Marrow Transplant 49:116–121

    Article  CAS  Google Scholar 

  10. Pidala JA, Hamilton BK, Martin PJ, Onstad L, Storer BE, Palmer J, Alousi A, Cutler C, Jagasia MH, Chen GL, Arora M, Flowers ME, Lee SJ (2019) The chronic graft-vs.-host disease failure-free survival (cGVHD-FFS) index. Biol Blood Marrow Transplant 25(12):P2468-2473

    Article  Google Scholar 

  11. Palmer J, Chai X, Pidala J, Inamoto Y, Martin PJ, Storer B, Pusic I, Flowers ME, Arora M, Pavletic SZ, Lee SJ (2016) Predictors of survival, nonrelapse mortality, and failure-free survival in patients treated for chronic graft-versus-host disease. Blood 127:160–166

    Article  CAS  Google Scholar 

  12. Malard F, Chevallier P, Guillaume T, Delaunay J, Rialland F, HarousseauJL Moreau P, Mechinaud F, Milpied N, Mohty M (2014) Continuous reduced nonrelapse mortality after allogeneic hematopoietic stem cell transplantation: a single-institution’s three decade experience. Biol Blood Marrow Transplant 20(8):1217–23

    Article  Google Scholar 

  13. Arora M, Cutler CS, Jagasia MH, Pidala J, Chai X, Martin PJ, Flowers ME, Inamoto Y, Chen GL, Wood WA, Khera N, Palmer J, Duong H, Arai S, Mayer S, Pusic I, Lee SJ (2016) Late acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 22(3):449–455

    Article  Google Scholar 

  14. Pallua S, Giesinger J, Oberguggenberger A, Kemmler G, Nachbaur D, Clausen J, Kopp M, Sperner-Unterweger B, Holzner B (2010) Impact of GvHD on quality of life in long-term survivors of haematopoietic transplantation. Bone Marrow Transplant 45(10):1534–1539

    Article  CAS  Google Scholar 

  15. El-Jawahri A, Pidala J, Inamoto Y, Chai X, Khera N, Wood WA, Cutler C, AroraM Carpenter PA, Palmer J, Flowers M, Weisdorf D, Pavletic S, Jaglowski S, Jagasia M, Lee SJ, Chen YB (2014) Impact of age on quality of life, functional status, and survival in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant 20(9):1341–8

    Article  Google Scholar 

  16. Kruse AL, Grätz 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. https://doi.org/10.1186/1758-3284-1-29

    Article  PubMed  PubMed Central  Google Scholar 

  17. Demarosi F, Lodi G, Carrassi A, Soligo D, Sardella A (2005) Oral malignancies following HSCT: graft versus host disease and other risk factors. Oral Oncol 41(9):865–877. https://doi.org/10.1016/j.oraloncology.2005.02.001

    Article  PubMed  Google Scholar 

  18. Nicolatou-Galitis O, Kitra V, Van Vliet-Constantinidou C, Peristeri J, Goussetis E, Petropoulos D, Grafakos S (2001) The oral manifestations of chronic graft-versus-host disease (cGVHD) in paediatric allogeneic bone marrow transplant recipients. J Oral Pathol Med 30(3):148–153

    Article  CAS  Google Scholar 

  19. Martin PJ (2008) Biology of chronic graft-versus-host disease: implications for a future therapeutic approach. Keio J Med 57(4):177–183

    Article  Google Scholar 

  20. Gomes AO, Torres SR, Maiolino A, Dos Santos CW, Silva Junior A, Correa ME, Moreira MC, Gonçalves LS (2014) Early and late oral features of chronic graft-versus-host disease. RevBrasHematolHemoter 36:43–49

    Google Scholar 

  21. Flowers ME, Inamoto Y, Carpenter PA, Lee SJ, Kiem HP, Petersdorf EW, Pereira SE, Nash RA, Mielcarek M, Fero ML, Warren EH, Sanders JE, Storb RF, Appelbaum FR, Storer BE, Martin PJ (2011) Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood 117(11):3214–3219

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Stomatology Department, A.C. Camargo Cancer Center, Rua Prof. Antônio Prudente, 211 - Liberdade, São Paulo, SP, 01509-010, Brazil

    Ana Cláudia Scaraficci, Patrícia Maria Fernandes, Fabio Abreu Alves & Graziella Chagas Jaguar

  2. Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas – UNICAMP – Piracicaba, Piracicaba, Brazil

    Patrícia Maria Fernandes

  3. Department of Hematology, Hematopoietic Stem Cell Transplant Unit, A.C. Camargo Cancer Center, São Paulo, Brazil

    Jayr Schmidt Filho

Authors
  1. Ana Cláudia Scaraficci
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  2. Patrícia Maria Fernandes
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  3. Fabio Abreu Alves
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  4. Jayr Schmidt Filho
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  5. Graziella Chagas Jaguar
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Contributions

All authors wrote the manuscript.

Corresponding author

Correspondence to Graziella Chagas Jaguar.

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Ethics approval

The study was approved by the Ethics Committee of Hospital A.C.Camargo, São Paulo, Brazil (n 1694/12).

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All authors approved the manuscript for publication.

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Scaraficci, A.C., Fernandes, P.M., Abreu Alves, F. et al. Oral manifestations of graft-versus-host disease in patients submitted to allogeneic hematopoietic stem cell transplantation: the experience of a Brazilian Cancer Center . Support Care Cancer 30, 567–573 (2022). https://doi.org/10.1007/s00520-021-06349-9

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  • DOI: https://doi.org/10.1007/s00520-021-06349-9

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