Supportive Care in Cancer

, Volume 13, Issue 10, pp 790–796 | Cite as

A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients

  • N. M. A. Blijlevens
  • J. P. Donnelly
  • A. H. J. Naber
  • A. V. M. B. Schattenberg
  • B. E. dePauw
Original Article


We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day −6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p=0.001) whilst citrulline was lower (p=0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32±4 versus 37±3, p=0.001) whilst CRP was higher (74±48 versus 34±38, p=0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications.


  1. 1.
    Lacey JM, Wilmore DW (1990) Is glutamine a conditionally essential amino acid? Nutr Rev 48(8):297–309Google Scholar
  2. 2.
    Klimberg VS, McClellan JL, Organ CH Jr (1996) Honorary lectureship. Glutamine, cancer, and its therapy. Am J Surg 172(5):418–424CrossRefPubMedGoogle Scholar
  3. 3.
    Ziegler TR (2001) Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. J Nutr 131:2578S–2584SGoogle Scholar
  4. 4.
    Anderson PM, Ramsay NKC, Shu XO, Rydholm N, Rogosheske J, Nicklow R et al (1998) Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant 22(4):339–344Google Scholar
  5. 5.
    Blijlevens NMA, 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 25:1269–1278Google Scholar
  6. 6.
    Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB (2003) The burdens of cancer therapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98:1531–1539CrossRefPubMedGoogle Scholar
  7. 7.
    Rapoport AP, Miller Watelet LF, Linder T, Rberly S, Raubertas RF, Lipp J et al (1999) Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants. J Clin Oncol 17:2446–2453Google Scholar
  8. 8.
    Sonis ST, Oster G, Fuchs H, Bellm L, Bradford WZ, Edelsberg J et al (2001) Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol 19(8):2201–2205PubMedGoogle Scholar
  9. 9.
    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(6):409–413Google Scholar
  10. 10.
    Blijlevens NMA, van’t Land B, Donnelly JP, M’Rabet L, DePauw BE (2004) Measuring mucosal damage induced by cytotoxic therapy. Support Care Cancer 12:227–233Google Scholar
  11. 11.
    Blijlevens NMA, Lutgens LCHW, Schattenberg AVMB, De Pauw BE (2004) Citrulline: a potentially simple quantitative marker of intestinal epithelial damage following myeloablative therapy. Bone Marrow Transplant 34(3):193–196Google Scholar
  12. 12.
    Schaap N, Schattenberg A, Bar B, Preijers F, Geurts van Kessel A, van der Maazen R et al (1997) Outcome of transplantation for standard-risk leukaemia with grafts depleted of lymphocytes after conditioning with an intensified regimen. Br J Haematol 98:750–759Google Scholar
  13. 13.
    Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41PubMedGoogle Scholar
  14. 14.
    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(6):409–413Google Scholar
  15. 15.
    Jansen G, Muskiet FAJ, Schierbeek H, Berger R, Van melle G (1986) Capillary gas chromatographic profiling of urinary, plasma and erythrocyte sugars and polyols as their trimethylsilyl derivates, preceded by a simple and rapid prepurification method. Clin Chim Acta 157:277–294Google Scholar
  16. 16.
    Johnston JD, Harvey CJ, Menzies IS, Treacher DF (1996) Gastrointestinal permeability and absorptive capacity in sepsis. Crit Care Med 24:1144–1149Google Scholar
  17. 17.
    Lim SG, Menzies IS, Lee CA, Johnson MA, Pounder RE (1993) Intestinal permeability and function in patients infected with Human Immunodeficiency Virus: a comparison with Coeliac Disease. Scand J Gastroenterol 28:573–580Google Scholar
  18. 18.
    Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E, Prochazka B et al (2004) Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study. Bone Marrow Transplant 30:953–961Google Scholar
  19. 19.
    Lutgens LC, Blijlevens NM, Deutz NE, Donnelly JP, Lambin P, de Pauw BE (2005) Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration: a comparison with sugar permeability tests. Cancer 103(1):191–199Google Scholar
  20. 20.
    Canovas G, Leon-Sanz M, Gomez P, Angeles Valero M, Gomis P, La Huerta JJ (2000) Oral glutamin supplements in autologous hematopoietic transplants: impact on gastro-intestinal toxicity and plasma protein levels. Haematologica 85(11):1229–1230Google Scholar
  21. 21.
    Piccirillo N, De Matteis S, Laurenti L, Chiusolo P, Sora F, Pittiruti M et al (2003) Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: effects on immune reconstitution and mucositis. Haematologica 88(2):192–200Google Scholar
  22. 22.
    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. A randomized, double-blind, controlled study. Ann Intern Med 116(10):821–828Google Scholar
  23. 23.
    Schloerb PR, Amare M (1993) Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study) [see comments]. J Parenter Enter Nutr 17(5):407–413Google Scholar
  24. 24.
    Jonas CR, Puckett AB, Jones DP, Griffith DP, Szesycki EE, Bergman GF et al (2000) Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients. Am J Clin Nutr 72:181–189Google Scholar
  25. 25.
    Brown SA, Goringe A, Fegan C, Davies SV, Giddings J, Whittaker JA et al (1998) Parenteral glutamine protects hepatic function during bone marrow transplantation. Bone Marrow Transplant 22(3):281–284Google Scholar
  26. 26.
    Slaviero KA, Clarke SJ, Rivory LP (2003) Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol 4(4):224–232Google Scholar
  27. 27.
    Chen YL, Le V, Leneveu A, Dreyfus F, Stheneur A, Florentin I et al (1994) Acute-phase response, interleukin-6, and alteration of cyclosporine pharmacokinetics. Clin Pharmacol Ther 55(6):649–660Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • N. M. A. Blijlevens
    • 1
  • J. P. Donnelly
    • 1
  • A. H. J. Naber
    • 2
  • A. V. M. B. Schattenberg
    • 1
  • B. E. dePauw
    • 1
  1. 1.Department of HaematologyUniversity Medical Centre St. Radboud NijmegenNijmegenThe Netherlands
  2. 2.Department of Gastroenterology and HepatologyUniversity Medical Centre St. Radboud NijmegenNijmegenThe Netherlands

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