Citrulline as a marker for chemotherapy induced mucosal barrier injury in pediatric patients.
BACKGROUND
The currently used National Cancer Institute (NCI) adverse events criteria for mucosal barrier injury (MBI) are insufficient for use in children. We searched for objective, easily measurable indicators for MBI in children with cancer.


OBJECTIVE
In children with acute myeloid leukemia, various MBI-related clinical and laboratory tests were investigated, reflecting clinical severity (NCI symptomatic adverse events criteria (gold standard), daily gut score (DGS)), inflammation (plasma and fecal interleukin-8 (IL-8), fecal calprotectin), enterocytic loss (plasma citrulline, ratio fecal human DNA/total DNA) and intestinal permeability (sugar absorption tests).


RESULTS
Intestinal MBI as detected by the NCI adverse events criteria was found in 55% of chemotherapy cycles, correlating well with the continuous DGS (n = 55, rho = 0.581; P < 0.001). Intestinal cell loss as measured by the ratio fecal human DNA/total DNA and plasma citrulline correlated well with both NCI criteria (n = 61, rho = 0.357, P = 0.005 resp. n = 58, rho = -0.482; P < 0.001) and DGS (n = 54, rho = 0.352, P = 0.009 resp. n = 55, rho = -0.625; P < 0.001). Plasma IL-8 correlated strongly to plasma citrulline (n = 46, rho = -0.627; P < 0.001).


CONCLUSIONS
MBI was reflected by parameters indicating inflammation (IL-8) and cell loss (plasma citrulline, ratio fecal human DNA/total DNA). We conclude that plasma citrulline might be a good parameter for MBI. Further studies are needed to show whether plasma citrulline can be used as a marker for MBI in future research.
van Vliet
Michel J
MJ
Division of Pediatric Oncology/Hematology, Beatrix Children's Hospital, University of Groningen, Groningen, The Netherlands.
Tissing
Wim J E
WJ
Rings
Edmond H H M
EH
Koetse
Harma A
HA
Stellaard
Frans
F
Kamps
Willem A
WA
de Bont
Eveline S J M
ES
D000208:Acute Disease; D000293:Adolescent; D000677:Amsacrine / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers; D002241:Carbohydrates / Q000009:adverse effects / Q000493:pharmacokinetics; D016923:Cell Death; D002648:Child; D002675:Child, Preschool; D002956:Citrulline / Q000097:blood*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004247:DNA / Q000032:analysis / Q000302:isolation & purification; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D020895:Enterocytes / Q000737:chemistry / Q000473:pathology; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000032:analysis / Q000097:blood; D007408:Intestinal Absorption; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D008954:Models, Biological; D052016:Mucositis / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D013280:Stomatitis / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism
D015415:Biomarkers; D002241:Carbohydrates; D016209:Interleukin-8; D039841:Leukocyte L1 Antigen Complex; D000677:Amsacrine; D003561:Cytarabine; D002956:Citrulline; D005047:Etoposide; D004247:DNA; D008942:Mitoxantrone; D003630:Daunorubicin