Annals of Hematology

, Volume 87, Issue 10, pp 837–845 | Cite as

Multivariate analysis of factors influencing oral mucositis in allogeneic hematopoietic stem cell transplantation

  • Yumiko Ohbayashi
  • Osamu Imataki
  • Hiroaki Ohnishi
  • Akinori Iwasaki
  • Takaaki Ogawa
  • Noriko Inagaki
  • Hiroe Shigeta
  • Yukiko Ohue
  • Taizo Tasaka
  • Akira Kitanaka
  • Yoshitsugu Kubota
  • Terukazu Tanaka
  • Toshihiko Ishida
  • Minoru Miyake
Original Article

Abstract

Little information is available regarding the effect of oral intervention on the outcome of hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the incidence of oral mucositis after allogeneic HSCT with or without oral intervention among 96 consecutive patients in our hospital between January 1988 and March 2006. We combined two oral intervention strategies: cryotherapy and oral health care. The former was applied beginning in 2003 for patients being treated with melphalan, and the latter, which was the study’s main strategy, was applied to all HSCT recipients beginning in 2004. Oral mucositis was evaluated according to NCI CTCAE v3.0. The incidence of oral mucositis was 30.9% (17/55) in reduced-intensity stem cell transplantation (RIST), which was significantly lower than the 90.2% (37/41) in conventional stem cell transplantation (CST; P < 0.001). Among these 96 patients, severe oral mucositis was observed in 19 (46.3%) CST cases and in 6 (10.9%) RIST cases (P < 0.001). The occurrence of oral mucositis apparently decreased after oral health care instructions were given. Multiple logistic analysis revealed that the conditioning regimen and oral health care were independent risk factors for the incidence of oral mucositis. The cryotherapy did not exert enough potency to prevent oral mucositis in patients who had undergone CST or RIST. We concluded that oral health care improved tissue damage due to an overall upgrade in oral hygiene during chemotherapy.

Keywords

Oral mucositis Allogeneic hematopoietic stem cell transplantation (HSCT) Multivariate analysis Risk factors 

References

  1. 1.
    Donnelly JP, Muus P, Schattenberg A, De Witte T, Horrevorts A, DePauw BE (1992) A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients. Bone Marrow Transplant 9:409–413. MedlinePubMedGoogle Scholar
  2. 2.
    Blijlevens NM, Donnelly JP, De Pauw BE (2000) Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview. Bone Marrow Transplant 25:1269–1278. Medline. DOI 10.1038/sj.bmt.1702447 PubMedCrossRefGoogle Scholar
  3. 3.
    Wardley AM, Jayson GC, Swindell R, Morgenstern GR, Chang J, Bloor R, Fraser CJ, Scarffe JH (2000) Prospective evaluation of oral mucositis in patients receiving myeloablative conditioning regimens and haemopoietic progenitor rescue. Br J Haematol 110:292–299. Medline. DOI 10.1046/j.1365-2141.2000.02202.x PubMedCrossRefGoogle Scholar
  4. 4.
    Dodd MJ, Dibble S, Miaskowski C, Paul S, Cho M, MacPhail L, Greenspan D, Shiba G (2001) A comparison of the affective state and quality of life of chemotherapy patients who do and do not develop chemotherapy-induced oral mucositis. J Pain Symptom Manage 21:498–505. Medline. DOI 10.1016/S0885-3924(01)00277-9 PubMedCrossRefGoogle Scholar
  5. 5.
    Scully C, Sonis S, Diz PD (2006) Oral mucositis. Oral Dis 12:229–241. Medline. DOI 10.1111/j.1601–0825.2006.01258.x PubMedCrossRefGoogle Scholar
  6. 6.
    Gruber U, Fegg M, Buchmann M, Kolb HJ, Hiddemann W (2003) The long-term psychosocial effects of haematopoietic stem cell transplantation. Eur J Cancer Care (Engl) 12:249–256. Medline. DOI 10.1046/j.1365-2354.2003.t01-1-00411.x CrossRefGoogle Scholar
  7. 7.
    Worthington HV, Clarkson JE, Eden OB (2006) Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 19:CD000978Google Scholar
  8. 8.
    Sonis ST, Oster G, Fuchs H, Bellm L, Bradford WZ, Edelsberg J, Hayden V, Eilers J, Epstein JB, LeVeque FG, Miller C, Peterson DE, Schubert MM, Spijkervet FK, Horowitz M (2001) Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol 19:2201–2205. MedlinePubMedGoogle Scholar
  9. 9.
    Robien K, Schubert MM, Bruemmer B, Lloid ME, Potter JD, Ulrich CM (2004) Predictors of oral mucositis in patients receiving hematopoietic cell transplants for chronic myelogenous leukemia. J Clin Oncol 22:1268–1275. Medline. DOI 10.1200/JCO.2004.05.147 PubMedCrossRefGoogle Scholar
  10. 10.
    Bensadoun RJ, Schubert MM, Lalla RV, Keefe D (2006) Amifostine in the management of radiation-induced and chemo-induced mucositis. Support Care Cancer 14:566–572. Medline. DOI 10.1007/s00520-006-0047-4 PubMedCrossRefGoogle Scholar
  11. 11.
    Piccirillo N, De Matteis S, Laurenti L, Chiusolo P, Sorà F, Pittiruti M, Rutella S, Cicconi S, Fiorini A, D’Onofrio G, Leone G, Sica S (2003) Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: effects on immune reconstitution and mucositis. Haematologica 88:192–200. MedlinePubMedGoogle Scholar
  12. 12.
    Blazar BR, Weisdorf DJ, Defor T, Goldman A, Braun T, Silver S, Ferrara JL (2006) Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Blood 108:3216–3222. Medline. DOI 10.1182/blood-2006-04-017780 PubMedCrossRefGoogle Scholar
  13. 13.
    Keefe D, Lees J, Horvath N (2006) Palifermin for oral mucositis in the high-dose chemotherapy and stem cell transplant setting: the Royal Adelaide Hospital Cancer Centre experience. Support Care Cancer 14:580–582. Medline. DOI 10.1007/s00520-006-0048-3 PubMedCrossRefGoogle Scholar
  14. 14.
    Mahood DJ, Dose AM, Loprinzi CL, Veeder MH, Athmann LM, Therneau TM, Sorensen JM, Gainey DK, Mailliard JA, Gusa NL et al (1991) Inhibition of fluorouracil-induced stomatitis by oral cryotherapy. J Clin Oncol 9:449–452. MedlinePubMedGoogle Scholar
  15. 15.
    Rocke LK, Loprinzi CL, Lee JK, Kunselman SJ, Iverson RK, Finck G, Lifsey D, Glaw KC, Stevens BA, Hatfield AK et al (1993) A randomized clinical trial of two different durations of oral cryotherapy for prevention of 5-fluorouracil-related stomatitis. Cancer 72:2234–2238. Medline. DOI 10.1002/1097-0142(19931001)72:7<2234::AID-CNCR2820720728>3.0.CO;2-NPubMedCrossRefGoogle Scholar
  16. 16.
    Mori T, Yamazaki R, Aisa Y, Nakazato T, Kudo M, Yashima T, Kondo S, Ikeda Y, Okamoto S (2006) Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients. Support Care Cancer 14:392–395. Medline. DOI 10.1007/s00520-005-0016-3 PubMedCrossRefGoogle Scholar
  17. 17.
    Bolwell B, Sobecks R, Pohlman B, Andresen S, Rybicki L, Kuczkowski E, Kalaycio M (2004) A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation. Bone Marrow Transplant 34:621–625. Medline. DOI 10.1038/sj.bmt.1704647 PubMedCrossRefGoogle Scholar
  18. 18.
    Elad S, Garfunkel AA, Or R, Michaeli E, Shapira MY, Galili D (2003) Time limitations and the challenge of providing infection-preventing dental care to hematopoietic stem-cell transplantation patients. Support Care Cancer 11:674–677. Medline. DOI 10.1007/s00520-003-0499-8 PubMedCrossRefGoogle Scholar
  19. 19.
    McGuire DB (2003) Barriers and strategies in implementation of oral care standards for cancer patients. Support Care Cancer 11:435–441. Medline. DOI 10.1007/s00520-003-0466-4 PubMedCrossRefGoogle Scholar
  20. 20.
    Yeager KA, Webster J, Crain M, Kasow J, McGuire DB (2000) Implementation of an oral care standard for leukemia and transplantation patients. Cancer Nurs 23:40–47. Medline. DOI 10.1097/00002820-200002000-00006 PubMedCrossRefGoogle Scholar
  21. 21.
    Melkos AB, Massenkeil G, Arnold R, Reichart PA (2003) Dental treatment prior to stem cell transplantation and its influence on the posttransplantation outcome. Clin Oral Investig 7:113–115. Medline. DOI 10.1007/s00784-003-0209-4 PubMedCrossRefGoogle Scholar
  22. 22.
    O’Leary TJ, Drake RB, Naylor JE (1972) The plaque control record. J Periodontol 43:38. MedlinePubMedGoogle Scholar
  23. 23.
    Sonis ST (2004) Oral mucositis in cancer therapy. J Support Oncol 2:3–8. MedlinePubMedGoogle Scholar
  24. 24.
    Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB, Mucositis Study Section of the Multinational Association for Supportive Care in Cancer, International Society for Oral Oncology (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Mucositis Study Section of the Multinational Association for Supportive Care in CancerInternational Society for Oral Oncology Cancer 100:1995–2025. Medline. DOI 10.1002/cncr.20162 PubMedCrossRefGoogle Scholar
  25. 25.
    Vokurka S, Bystricka E, Koza V, Scudlova J, Pavlicova V, Valentova D, Bockova J, Misaniova L (2005) The comparative effects of povidone-iodine and normal saline mouthwashes on oral mucositis in patients after high-dose chemotherapy and APBSCT–results of a randomized multicentre study. Support Care Cancer 13:554–558. Medline. DOI 10.1007/s00520-005-0792-9 PubMedCrossRefGoogle Scholar
  26. 26.
    Vokurka S, Bystricka E, Koza V, Scudlova J, Pavlicova V, Valentova D, Bockova J, Misaniova L (2006) Higher incidence of chemotherapy induced oral mucositis in females: a supplement of multivariate analysis to a randomized multicentre study. Support Care Cancer 14:974–976. Medline. DOI 10.1007/s00520-006-0031-z PubMedCrossRefGoogle Scholar
  27. 27.
    Bondi E, Baroni C, Prete A, Gatti M, Carrassi A, Lodi G, Porter SR (1997) Local antimicrobial therapy of oral mucositis in paediatric patients undergoing bone marrow transplantation. Oral Oncol 33:322–326. MedlinePubMedCrossRefGoogle Scholar
  28. 28.
    Ferretti GA, Ash RC, Brown AT, Largent BM, Kaplan A, Lillich TT (1987) Chlorhexidine for prophylaxis against oral infections and associated complications in patients receiving bone marrow transplants. J Am Dent Assoc 114:461–467. MedlinePubMedGoogle Scholar
  29. 29.
    Weisdorf DJ, Bostrom B, Raether D, Mattingly M, Walker P, Pihlstrom B, Ferrieri P, Haake R, Goldman A, Woods W et al (1989) Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse. Bone Marrow Transplant 4:89–95. MedlinePubMedGoogle Scholar
  30. 30.
    Foote RL, Loprinzi CL, Frank AR, O’Fallon JR, Gulavita S, Tewfik HH, Ryan MA, Earle JM, Novotny P (1994) Randomized trial of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis. J Clin Oncol 12:2630–2633. MedlinePubMedGoogle Scholar
  31. 31.
    Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809–1820. Medline. DOI 10.1016/S0140-6736(05)67728-8 PubMedCrossRefGoogle Scholar
  32. 32.
    Landa AS, van der Mei HC, Busscher HJ (1997) Detachment of linking film bacteria from enamel surfaces by oral rinses and penetration of sodium lauryl sulphate through an artificial oral biofilm. Adv Dent Res 11:528–538. MedlinePubMedCrossRefGoogle Scholar
  33. 33.
    Attarzadeh F (1990) Water irrigating devices for the orthodontic patient. Int J Orthod 28:17–22. MedlinePubMedGoogle Scholar
  34. 34.
    Scannapieco FA (2006) Pneumonia in nonambulatory patients: The role of oral bacteria and oral hygiene. Am Dent Assoc 137:21S–25SGoogle Scholar
  35. 35.
    Petersen PE (2003) The World Oral Health Report 2003: continuous improvement of oral health in the 21st century–the approach of the WHO Global Oral Health Programme. Community Dent Oral Epidemiol 31:3–23. Medline. DOI 10.1046/j..2003.com122.x PubMedCrossRefGoogle Scholar
  36. 36.
    Hellstrom MK, Ramberg P, Krok L, Lindhe J (1996) The effect of supragingival plaque control on the subgingival microflora in human periodontitis. J Clin Periodontol 23:934–940. Medline. DOI 10.1111/j.1600-051X.1996.tb00514.x PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Yumiko Ohbayashi
    • 1
  • Osamu Imataki
    • 2
  • Hiroaki Ohnishi
    • 2
  • Akinori Iwasaki
    • 1
  • Takaaki Ogawa
    • 1
  • Noriko Inagaki
    • 3
  • Hiroe Shigeta
    • 3
  • Yukiko Ohue
    • 3
  • Taizo Tasaka
    • 4
  • Akira Kitanaka
    • 5
  • Yoshitsugu Kubota
    • 6
  • Terukazu Tanaka
    • 7
  • Toshihiko Ishida
    • 8
  • Minoru Miyake
    • 1
  1. 1.Department of Oral and Maxillofacial Surgery, Faculty of MedicineKagawa UniversityKagawaJapan
  2. 2.Division of Hematology, Department of Internal Medicine, Faculty of MedicineKagawa UniversityKagawaJapan
  3. 3.Hematology & Stem Cell Transplantation Ward, Faculty of MedicineKagawa UniversityKagawaJapan
  4. 4.Department of Clinical Pathology and Laboratory MedicineKawasaki Medical SchoolOkayamaJapan
  5. 5.Department of Laboratory Medicine, Faculty of MedicineKagawa UniversityKagawaJapan
  6. 6.Department of Transfusion Medicine, Faculty of MedicineKagawa UniversityKagawaJapan
  7. 7.Environmental Health Sciences, Faculty of MedicineKagawa UniversityKagawaJapan
  8. 8.Department of Internal Medicine, Faculty of MedicineKagawa UniversityKagawaJapan

Personalised recommendations