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Annals of Oncology Advance Access originally published online on August 25, 2008
Annals of Oncology 2009 20(2):337-342; doi:10.1093/annonc/mdn579
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

quality of life/supportive care/palliative care

Loss of enterocyte mass is accompanied by diminished turnover of enterocytes after myeloablative therapy in haematopoietic stem-cell transplant recipients

J. P. M. Derikx1, N. M. A. Blijlevens2, J. P. Donnelly2, H. Fujii3, T. Kanda4, A. A. van Bijnen1, E. Heineman1 and W. A. Buurman1,*

1 Department of Surgery, University Hospital Maastricht and Nutrition and Toxicology Research Institute (NUTRIM), Maastricht University, Maastricht
2 Department of Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
3 Division of Molecular and Cellular Biology, Department of Signal Transduction Research, Graduate School of Medical and Dental Sciences, Niigata University, Niigata and Division of Bioscience and Biotechnology, Department of Biochemistry, Interdisciplinary Graduate School of Science and Technology, Shinshu University, Kamiina Country
4 Department of Surgery, Niigata University School of Medicine, Niigata, Japan

* Correspondence to: Dr W. A. Buurman, Department of Surgery, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands. Tel: +31-43-3881499; Fax: +31-43-3884154; E-mail: w.buurman{at}ah.unimaas.nl

Background: Intestinal mucosal barrier injury (MBI), resulting from myeloablative conditioning for haematopoietic stem-cell transplantation (HSCT), is an important cause of morbidity. Despite its frequency, recognition presents a challenge, while the aetiology needs still to be unravelled. The relationship between enterocyte mass and enterocyte loss was explored by examining citrulline serum levels and by assessing circulating intestinal fatty acid-binding protein (I-FABP) and ileal bile acid-binding protein (I-BABP), proteins released by dying mature enterocytes.

Patients and methods: Thirty-four adult patients with haematological malignancy received allogeneic HSCT (HSCT day 0) 12 days after being given idarubicin, cyclophosphamide and total body irradiation as myeloablative conditioning, a regimen known to induce oral and intestinal MBI. Serum levels of citrulline, I-FABP and I-BABP were measured on HSCT days –12, –6, 0, +7, +14 and +21.

Results: Myeloablative conditioning resulted in a significant decrease in serum citrulline with the nadir on HSCT day +7; thereafter, levels rose gradually. Simultaneously, a significant decrease in I-FABP and I-BABP levels occurred from the day of transplant until day +14.

Conclusions: Simultaneous reduction and subsequent increase of citrulline and I-FABP and I-BABP levels following cytotoxic treatment show that enterocyte mass corresponds to lower rate of dying enterocytes, indicating reduced turnover of enterocytes. Assessment of enterocyte turnover and mass offers opportunities for evaluation of new MBI therapies.

Key words: enterocyte mass, enterocyte turnover, mucositis, myeloablative therapy

Received for publication January 25, 2008. Revision received April 8, 2008. Accepted for publication July 23, 2008.


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