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British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(8):1062–1066. doi: 10.1038/bjc.1997.508

A new in vitro assay for quantitation of chemotherapy-induced mucositis.

A N Wymenga 1, W T van der Graaf 1, F L Spijkervet 1, W Timens 1, H Timmer-Bosscha 1, W J Sluiter 1, E G de Vries 1, N H Mulder 1
PMCID: PMC2228089  PMID: 9376267

Abstract

Patients receiving high-dose chemotherapy (HD-CT) are at risk of severe mucositis. Most prevention studies evaluate the degree of mucositis on clinical, and therefore subjective, measurements. The aim of this study was to develop an objective in vitro assay of chemotherapy-induced mucositis. Twelve patients with locally advanced breast carcinoma received HD-CT followed by peripheral stem cell reinfusion. Before and twice weekly after HD-CT, the mucosa was evaluated by an oral washing, a buccal smear and the World Health Organization (WHO) toxicity grading; furthermore, blood leucocyte levels were determined. For the oral washings, the percentage of viable epithelial cells was determined by trypan blue dye exclusion and leucocytes were counted by fluorescence microscopy after incubation with acridine orange. Maturity of buccal cells was assessed by staining buccal smears for morphology according to Papanicolaou (Whitacker D and Williams V, 1994). Eight healthy volunteers served as controls. The mean percentage (+/- s.e.m.) of viable oral epithelial cells was stable in controls (44 +/- 2%). In patients, they increased after HD-CT, which was significant after day 7 compared with pretreatment (P < or = 0.05). In addition, a shift from mature to immature epithelial cells in buccal smears was observed. Oral leucocyte levels were closely correlated with the blood leucocyte counts. The WHO score followed the results of these other evaluations with some delay. The viability of buccal cells obtained by oral washings increases after HD-CT. This is possibly because of desquamation of the upper oral mucosa layer, with a shift from mature to more immature cells. These data can be quantitated, and this assay may therefore be useful in studies aimed at prevention of mucositis.

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Selected References

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  1. Birchall M. A., Winterford C. M., Allan D. J., Harmon B. V. Apoptosis in normal epithelium, premalignant and malignant lesions of the oropharynx and oral cavity: a preliminary study. Eur J Cancer B Oral Oncol. 1995 Nov;31B(6):380–383. doi: 10.1016/0964-1955(95)00048-8. [DOI] [PubMed] [Google Scholar]
  2. Chi K. H., Chen C. H., Chan W. K., Chow K. C., Chen S. Y., Yen S. H., Chao J. Y., Chang C. Y., Chen K. Y. Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol. 1995 Oct;13(10):2620–2628. doi: 10.1200/JCO.1995.13.10.2620. [DOI] [PubMed] [Google Scholar]
  3. Development of a staging system for chemotherapy-induced stomatitis. Western Consortium for Cancer Nursing Research. Cancer Nurs. 1991 Feb;14(1):6–12. [PubMed] [Google Scholar]
  4. Eilers J., Berger A. M., Petersen M. C. Development, testing, and application of the oral assessment guide. Oncol Nurs Forum. 1988 May-Jun;15(3):325–330. [PubMed] [Google Scholar]
  5. Gabrilove J. L., Jakubowski A., Scher H., Sternberg C., Wong G., Grous J., Yagoda A., Fain K., Moore M. A., Clarkson B. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N Engl J Med. 1988 Jun 2;318(22):1414–1422. doi: 10.1056/NEJM198806023182202. [DOI] [PubMed] [Google Scholar]
  6. Hickey A. J., Toth B. B., Lindquist S. B. Effect of intravenous hyperalimentation and oral care on the development of oral stomatitis during cancer chemotherapy. J Prosthet Dent. 1982 Feb;47(2):188–193. doi: 10.1016/0022-3913(82)90186-x. [DOI] [PubMed] [Google Scholar]
  7. Kenny S. A. Effect of two oral care protocols on the incidence of stomatitis in hematology patients. Cancer Nurs. 1990 Dec;13(6):345–353. [PubMed] [Google Scholar]
  8. Lieschke G. J., Ramenghi U., O'Connor M. P., Sheridan W., Szer J., Morstyn G. Studies of oral neutrophil levels in patients receiving G-CSF after autologous marrow transplantation. Br J Haematol. 1992 Nov;82(3):589–595. doi: 10.1111/j.1365-2141.1992.tb06472.x. [DOI] [PubMed] [Google Scholar]
  9. Lockhart P. B., Sonis S. T. Relationship of oral complications to peripheral blood leukocyte and platelet counts in patients receiving cancer chemotherapy. Oral Surg Oral Med Oral Pathol. 1979 Jul;48(1):21–28. doi: 10.1016/0030-4220(79)90230-5. [DOI] [PubMed] [Google Scholar]
  10. Peterson D. E. Oral toxicity of chemotherapeutic agents. Semin Oncol. 1992 Oct;19(5):478–491. [PubMed] [Google Scholar]
  11. Schmitz N., Linch D. C., Dreger P., Goldstone A. H., Boogaerts M. A., Ferrant A., Demuynck H. M., Link H., Zander A., Barge A. Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet. 1996 Feb 10;347(8998):353–357. doi: 10.1016/s0140-6736(96)90536-x. [DOI] [PubMed] [Google Scholar]
  12. Schubert M. M., Williams B. E., Lloid M. E., Donaldson G., Chapko M. K. Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation. Development of an oral mucositis index. Cancer. 1992 May 15;69(10):2469–2477. doi: 10.1002/1097-0142(19920515)69:10<2469::aid-cncr2820691015>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  13. Sheridan W. P., Morstyn G., Wolf M., Dodds A., Lusk J., Maher D., Layton J. E., Green M. D., Souza L., Fox R. M. Granulocyte colony-stimulating factor and neutrophil recovery after high-dose chemotherapy and autologous bone marrow transplantation. Lancet. 1989 Oct 14;2(8668):891–895. doi: 10.1016/s0140-6736(89)91552-3. [DOI] [PubMed] [Google Scholar]
  14. Sonis S. T., Costello K. A. A database for mucositis induced by cancer chemotherapy. Eur J Cancer B Oral Oncol. 1995 Jul;31B(4):258–260. doi: 10.1016/0964-1955(95)00019-e. [DOI] [PubMed] [Google Scholar]
  15. Sonis S. T., Lindquist L., Van Vugt A., Stewart A. A., Stam K., Qu G. Y., Iwata K. K., Haley J. D. Prevention of chemotherapy-induced ulcerative mucositis by transforming growth factor beta 3. Cancer Res. 1994 Mar 1;54(5):1135–1138. [PubMed] [Google Scholar]
  16. Sonis S. T., Tracey C., Shklar G., Jenson J., Florine D. An animal model for mucositis induced by cancer chemotherapy. Oral Surg Oral Med Oral Pathol. 1990 Apr;69(4):437–443. doi: 10.1016/0030-4220(90)90376-4. [DOI] [PubMed] [Google Scholar]
  17. Spijkervet F. K., van Saene H. K., Panders A. K., Vermey A., Mehta D. M. Scoring irradiation mucositis in head and neck cancer patients. J Oral Pathol Med. 1989 Mar;18(3):167–171. doi: 10.1111/j.1600-0714.1989.tb00756.x. [DOI] [PubMed] [Google Scholar]
  18. Toth B. B., Martin J. W., Fleming T. J. Oral complications associated with cancer therapy. An M. D. Anderson Cancer Center experience. J Clin Periodontol. 1990 Aug;17(7 ):508–515. doi: 10.1111/j.1365-2710.1992.tb01225.x. [DOI] [PubMed] [Google Scholar]
  19. Woo S. B., Sonis S. T., Monopoli M. M., Sonis A. L. A longitudinal study of oral ulcerative mucositis in bone marrow transplant recipients. Cancer. 1993 Sep 1;72(5):1612–1617. doi: 10.1002/1097-0142(19930901)72:5<1612::aid-cncr2820720520>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  20. Wright D. G., Meierovics A. I., Foxley J. M. Assessing the delivery of neutrophils to tissues in neutropenia. Blood. 1986 Apr;67(4):1023–1030. [PubMed] [Google Scholar]

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