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


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.
Derikx
J P M
JP
Department of Surgery, University Hospital Maastricht and Nutrition and Toxicology Research Institute (NUTRIM), Maastricht University, The Netherlands.
Blijlevens
N M A
NM
Donnelly
J P
JP
Fujii
H
H
Kanda
T
T
van Bijnen
A A
AA
Heineman
E
E
Buurman
W A
WA
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002352:Carrier Proteins / Q000097:blood; D002956:Citrulline / Q000097:blood; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D020895:Enterocytes / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000737:chemistry; D005260:Female; D019337:Hematologic Neoplasms / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D008970:Molecular Weight; D052016:Mucositis / Q000188:drug therapy / Q000473:pathology; D012015:Reference Standards; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014916:Whole-Body Irradiation / Q000009:adverse effects
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D008562:Membrane Glycoproteins; C037643:bile acid binding proteins; D002956:Citrulline; D003520:Cyclophosphamide; D015255:Idarubicin