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Therapy

Intestinal mucosal dysfunction and infection during remission-induction therapy for acute myeloid leukaemia

Leukemia volume 20, pages 2087–2092 (2006)Cite this article

Abstract

Intestinal barrier function was prospectively examined in the course of a clinical trial evaluating the efficacy and safety of lisofylline for reducing cytotoxic therapy-induced intestinal epithelial damage-related infectious morbidity in patients receiving standard remission-induction therapy for acute myeloid leukaemia. The absorption and permeation of oral D-Xylose, lactulose and mannitol were measured weekly from baseline until marrow recovery in adult recipients of idarubicin plus cytarabine for untreated acute myeloid leukaemia. These studies were correlated with non-haematologic chemotherapy-related toxicities reflecting mucosal damage, including nausea, vomiting, stomatitis, diarrhoea, abdominal pain and systemic infection. D-xylose absorption decreased and lactulose:mannitol ratio reflecting intestinal permeability increased from baseline until the second and third week after the beginning of the treatment followed by recovery. These measures correlated with infection rates, nausea, vomiting, diarrhoea and increased blood product utilization. Lisofylline was associated with increased intestinal permeability, nausea, vomiting and infection-related morbidity despite a reduction in the duration of neutropaenia. These surrogates of intestinal barrier function correlated well with clinically important outcomes despite the failure to demonstrate reduced morbidity with lisofylline and represent useful objective outcome measurements for future clinical trials of products for the amelioration of the effects of cytotoxic therapy on the intestinal mucosa.

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Acknowledgements

We would like to acknowledge and thank the staff of the GD6 Oncology Unit, the Health Sciences Centre, Winnipeg, for their assistance in the care of the patients and in the conduct of this study. Further, we would like to thank Mrs Barbara Freed, Ms Jacquie Thiessen, Mrs Ruth Loewen RN and Mrs Kathy Ramesar RN for their meticulous work in the data collection and management and Mary Cheang M Math for her statistical advice. Funding for this work was derived from a grant-in-aid from Biochem Therapeutics Inc., Montreal, Québec, Canada and Cell Therapeutics Inc., Seattle, WA, USA. The substance of this paper represents original research designed and conducted by EJB. JBM collaborated on the intestinal permeability studies. The results of this study have not been previously presented or published. Interpretation of the study results and discussions regarding publication were made by the investigators without participation of the sponsor. The protocol was approved by the Committee on Use of Human Subjects in Research, the University of Manitoba. All patients provided informed written consent.

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Authors and Affiliations

  1. Departments of Internal Medicine and Medical Microbiology, The University of Manitoba, Winnipeg, Manitoba, Canada

    E J Bow

  2. Department of Medical Oncology and Haematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada

    E J Bow

  3. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

    J B Meddings

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  1. E J Bow
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Correspondence to E J Bow.

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Bow, E., Meddings, J. Intestinal mucosal dysfunction and infection during remission-induction therapy for acute myeloid leukaemia. Leukemia 20, 2087–2092 (2006). https://doi.org/10.1038/sj.leu.2404440

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