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The effect of high-dose enteral glutamine on the incidence and severity of mucositis in paediatric oncology patients

European Journal of Clinical Nutrition volume 63, pages 134–140 (2009)Cite this article

Abstract

Background/Objective:

The study was conducted to determine if enteral glutamine, 0.65 g kg−1 daily for 7 days, is effective in reducing the incidence and severity of mucositis in paediatric oncology patients when given alongside chemotherapy. The study was carried out at St James's University Hospital, Leeds, UK.

Subjects/Methods:

This was a randomized study using the patients as their own controls. Seventy-six patients undergoing treatment for paediatric malignancy having at least two identical courses of chemotherapy and at risk of developing mucositis participated in the study. Patients received one course of chemotherapy with glutamine and an identical course without. Alternate patients were allocated to have glutamine with course 1 or with course 2. The severity of symptoms of mucositis and the duration of enteral and parenteral nutrition were recorded. Daily ammonia levels were measured.

Results:

Fifty patients completed the study. No statistical significance with regard to symptoms of mucositis was found. Fewer children receiving glutamine required parenteral nutrition (P=0.049), and the duration of parenteral nutrition was less (P=0.023). No adverse effects attributed to taking the glutamine were observed.

Conclusions:

The study showed that high-dose enteral glutamine did not reduce the incidence and severity of oral mucositis as determined by subjective toxicity measurements, but did show a significant reduction in parenteral nutrition usage. No adverse cumulative effect of this oral glutamine dose was observed.

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References

  • Anderson PM, Schroeder G, Skubitz KM (1998). Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 83, 1433–1439.

    Article  CAS  Google Scholar 

  • Aquino VM, Harvey AR, Garvin JH, Godder KT, Nieder ML, Adams RH et al. (2005). A double-blind randomised placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing haematopoietic stem cell transplantation: a paediatric blood and marrow transplant consortium study. Bone Marrow Transplant 36, 611–616.

    Article  CAS  Google Scholar 

  • Buchman AL (1996). Glutamine: is it a conditionally required nutrient for the human gastrointestinal system? J Am Coll Nutr 15, 199–205.

    Article  CAS  Google Scholar 

  • Buchman AL, Moukarzel AA, Bhuta S, Belle M, Ament ME, Eckhert CD et al. (1995). Parenteral nutrition is associated with intestinal morphologic and functional changes in humans. J Parenter Enteral Nutr 19, 453–460.

    Article  CAS  Google Scholar 

  • Cockerham MB, Weinberger BB, Lerchie SB (2000). Oral glutamine for the prevention of oral mucositis associated with high-dose Paclitaxel and Melphalan for autologous bone marrow transplantation. Ann Pharmacother 34, 300–303.

    Article  CAS  Google Scholar 

  • Duncan M, Grant G (2003). Review article: oral and intestinal mucositis—causes and possible treatments. Aliment Pharmacol Ther 18, 853–874.

    Article  CAS  Google Scholar 

  • Gardiner KR, Kirk SJ, Rowlands BJ (1995). Novel substrates to maintain gut integrity. Nutr Res Rev 8, 43–64.

    Article  CAS  Google Scholar 

  • Green A (1988). When and how should we measure plasma ammonia. Ann Clin Biochem 25, 199–209.

    Article  CAS  Google Scholar 

  • Guedon C, Schmitz J, Lerebours E, Metayer J, Audran E, Hemet J et al. (1986). Decreased brush border hydrolase activities without gross morphologic changes in human intestinal mucosa after prolonged total parenteral nutrition of adults. Gastroenterology 90, 373–378.

    Article  CAS  Google Scholar 

  • Hall JC, Heel K, McCauley R (1996). Glutamine. Br J Surg 83, 305–312.

    Article  CAS  Google Scholar 

  • Jebb SA, Marcus R, Elia M (1995). A pilot study of oral glutamine supplementation in patients receiving bone marrow transplant. Clin Nutr 14, 162–165.

    Article  CAS  Google Scholar 

  • Lacey JM, Wilmore DW (1990). Is glutamine a conditionally essential amino acid? Nutr Rev 48, 297–309.

    Article  CAS  Google Scholar 

  • Lind MJ (1995). Cytotoxic chemotherapy. Medicine 422–426.

  • Miller AL (1999). Therapeutic considerations of L-glutamine: a review of literature. Altern Med Rev 4, 239–248.

    CAS  PubMed  Google Scholar 

  • Muscaritoli M, Micozzi A, Conversano L, Martino P, Petti MC, Cartoni C et al. (1997). Oral glutamine in the prevention of chemotherapy-induced gastrointestinal toxicity. Eur J Cancer 33, 319–320.

    Article  CAS  Google Scholar 

  • Peterson DE, Jones JB, Petit II RG (2007). Randomised, placebo-controlled trial of Saforis for the prevention and treatment of oral mucositis in breast cancer patients receiving anthrocycline-based chemotherapy. Cancer 109, 322–331.

    Article  CAS  Google Scholar 

  • Petit R, Shinal E, French C (2000). AES-14 facilitates rapid intracellular transport of high levels of L-glutamine in mucosal epithelial cells. Proc Am Soc Clin Oncol 19, 612a (Abstract 2410).

    Google Scholar 

  • Rhoads M (1999). Glutamine signalling in intestinal cells. J Parenter Enteral Nutr 23 (5 Suppl), S38–S40.

    Article  CAS  Google Scholar 

  • Savarese DMF, Savy G, Vahdat L, Wischmeyer PE, Corey B (2003). Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev 29, 501–513.

    Article  CAS  Google Scholar 

  • Schloerb PR, Skikne BS (1999). Oral and parenteral glutamine in bone marrow transplantation: a randomised, double blind study. J Parenter Enteral Nutr 23, 117–122.

    Article  CAS  Google Scholar 

  • Skubitz KM, Anderson PM (1996). Oral glutamine to prevent chemotherapy induced stomatitis; a pilot study. J Lab Clin Med 127, 223–228.

    Article  CAS  Google Scholar 

  • van Acker BAC, von Meyenfeldt MF, van der Hulst RRWJ, Hulsewe KWE, Wagenmakers AJM, Deutz NEP et al. (1999). Glutamine: the pivot of our nitrogen economy? J Parenter Enteral Nutr 23, S45–S48.

    Article  CAS  Google Scholar 

  • van Zaanen HCT, van der Lelie H, Trimmer JG, Frust P, Sauerwein HP (1994). Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy induced toxicity. Cancer 74, 2879–2884.

    Article  CAS  Google Scholar 

  • Ward E, Picton S, Reid U, Thomas D, Gardener C, Smith M et al. (2003). Oral glutamine in paediatric oncology patients: a dose finding study. Eur J Clin Nutr 56, 1–6.

    Google Scholar 

  • Ziegler TR, Benfell K, Smith RJ, Young LS, Brown E, Ferrari-Baliviera E et al. (1990). Safety and metabolic effects of L-glutamine administration in humans. J Parenter Enteral Nutr 14, 137S–146S.

    Article  CAS  Google Scholar 

  • Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R et al. (1992). Clinical and metabolic efficacy of glutamine supplemented parenteral nutrition after bone marrow transplantation. Ann Int Med 116, 821–828.

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to SHS International for providing the L-glutamine.

Author information

Authors and Affiliations

  1. Dietetic Department, St James's University Hospital, Leeds, UK

    E Ward

  2. Chemical Pathology Department, St James's University Hospital, Leeds, UK

    M Smith & M Henderson

  3. Yorkshire Regional Centre for Paediatric Oncology and Haematology, Leeds, UK

    U Reid, I Lewis, S Kinsey & S V Picton

  4. Biostatistics Unit, University of Leeds, Leeds, UK

    V Allgar & D Bowers

Authors
  1. E Ward
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  2. M Smith
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  3. M Henderson
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  4. U Reid
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  5. I Lewis
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  6. S Kinsey
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  7. V Allgar
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  8. D Bowers
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  9. S V Picton
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Corresponding author

Correspondence to E Ward.

Additional information

Guarantors: SV Picton and E Ward.

Contributors: EW initiated this study. The study design was developed in discussions involving EW, MS, MH, VA, IL, SK and SVP. EW, MS and UR conducted the study. Data analysis was done by EW and DB. All investigators except VA were involved in discussions on data interpretation. The paper was written by EW and SVP with contribution from MH.

Appendices

Appendix A

Table 6 Grading criteria
Full size table

Appendix B

Limited data were obtained from 19 of the 26 patients who failed to complete the study. Seven patients despite consenting to the study were complete non-starters and hence no data were obtained. The tables below give the results, however, as the data were not comparable, no statistics were done.

Table 7 Characteristics of the 19 patients who failed to complete the study
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Table 8 Patient outcomes on those who failed to complete
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Table 9 Toxicity outcomes grades 3 and grade 4 combined on patients who failed to complete
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Ward, E., Smith, M., Henderson, M. et al. The effect of high-dose enteral glutamine on the incidence and severity of mucositis in paediatric oncology patients. Eur J Clin Nutr 63, 134–140 (2009). https://doi.org/10.1038/sj.ejcn.1602894

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