TY - JOUR

T1 - Gastrointestinal barrier integrity and mucosal inflammation as risk factors of blood stream infections in children treated for acute lymphoblastic leukaemia

AU - De Pietri, Silvia

AU - Weischendorff, Sarah

AU - Rathe, Mathias

AU - Frandsen, Thomas Leth

AU - Hasle, Henrik

AU - Nersting, Jacob

AU - Nielsen, Claus H.

AU - Moser, Claus

AU - Müller, Klaus

N1 - Publisher Copyright: © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

PY - 2023

Y1 - 2023

N2 - Chemotherapy-induced mucositis increases the risk of blood stream infections (BSI) due to translocation of bacteria across the intestinal epithelium. Our study investigated if quantitative measures of intestinal mucositis severity, including plasma citrulline (a marker of functional enterocytes) and CCL20 (an intestinal immune homeostatic chemokine), could identify patients at risk of BSI. A total of 106 children with ALL undergoing induction treatment (NOPHO ALL 2008) were included and information regarding BSI episodes was collected from the patients' medical records. Twenty-seven patients (25%) developed BSI during induction. Patients with BSI had a larger decrease in citrulline after chemotherapy than patients without BSI, and nearly all BSI episodes (25/27) occurred in the group of patients exhibiting a drop in citrulline (OR = 6.4 [95% CI: 1.4-29.3], P =.008). Patients who developed BSI had higher plasma CCL20 levels on days 8, 15 and 22 than patients without BSI (all P <.05), and elevated CCL20 levels on day 8 increased the risk of subsequent BSI (OR = 1.57 [1.11-2.22] per doubling of CCL20 level, P =.01) in a multivariable logistic regression analysis. These findings suggest that children with ALL who develop BSI during chemotherapy are characterised by more severe intestinal mucositis, as measured by plasma citrulline and CCL20. These markers may be useful in early risk stratification to guide treatment decisions.

AB - Chemotherapy-induced mucositis increases the risk of blood stream infections (BSI) due to translocation of bacteria across the intestinal epithelium. Our study investigated if quantitative measures of intestinal mucositis severity, including plasma citrulline (a marker of functional enterocytes) and CCL20 (an intestinal immune homeostatic chemokine), could identify patients at risk of BSI. A total of 106 children with ALL undergoing induction treatment (NOPHO ALL 2008) were included and information regarding BSI episodes was collected from the patients' medical records. Twenty-seven patients (25%) developed BSI during induction. Patients with BSI had a larger decrease in citrulline after chemotherapy than patients without BSI, and nearly all BSI episodes (25/27) occurred in the group of patients exhibiting a drop in citrulline (OR = 6.4 [95% CI: 1.4-29.3], P =.008). Patients who developed BSI had higher plasma CCL20 levels on days 8, 15 and 22 than patients without BSI (all P <.05), and elevated CCL20 levels on day 8 increased the risk of subsequent BSI (OR = 1.57 [1.11-2.22] per doubling of CCL20 level, P =.01) in a multivariable logistic regression analysis. These findings suggest that children with ALL who develop BSI during chemotherapy are characterised by more severe intestinal mucositis, as measured by plasma citrulline and CCL20. These markers may be useful in early risk stratification to guide treatment decisions.

KW - acute lymphoblastic leukaemia

KW - blood stream infections

KW - CCL20

KW - citrulline

KW - intestinal mucositis

UR - http://www.scopus.com/inward/record.url?scp=85164192122&partnerID=8YFLogxK

U2 - 10.1002/ijc.34639

DO - 10.1002/ijc.34639

M3 - Journal article

C2 - 37387257

AN - SCOPUS:85164192122

VL - 153

SP - 1635

EP - 1642

JO - Acta - Unio Internationalis Contra Cancrum

JF - Acta - Unio Internationalis Contra Cancrum

SN - 0898-6924

IS - 9

ER -