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

Pietri, Silvia; Weischendorff, Sarah; Rathe, Mathias; Frandsen, Thomas Leth; Hasle, Henrik; Nersting, Jacob; Nielsen, Claus Henrik; Moser, Claus; Müller, Klaus

doi:10.1002/ijc.34639

Cited by 5 publications

(1 citation statement)

References 61 publications

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“…Chemotherapy-induced mucositis poses a significant adverse reaction for cancer patients undergoing treatment, characterized by painful inflammation and ulceration of the gastrointestinal mucosa 1 , 2 . This condition not only elicits symptoms like anorexia, vomiting, and diarrhea, but can also result in treatment delays or even cessation 3 , 4 . A substantial portion, approximately 40%–80%, of cancer patients undergoing chemotherapy are affected by mucositis 5 .…”

Section: Introductionmentioning

confidence: 99%

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

Bai,

Zhao,

Wang

et al. 2024

Acta Pharmaceutica Sinica B

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Section: Introductionmentioning

confidence: 99%

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

Bai,

Zhao,

Wang

et al. 2024

Acta Pharmaceutica Sinica B

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Intestinal mucositis, systemic inflammation and bloodstream infections following high‐dose methotrexate treatment in childhood acute lymphoblastic leukaemia: Comparison between the NOPHO ALL 2008 protocol and the ALLTogether1 protocol

Weischendorff,

de Pietri,

Rathe

et al. 2024

Intl Journal of Cancer

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Severe intestinal mucositis (IM) increases the risk of bloodstream infections (BSI) and inflammatory toxicity during acute lymphoblastic leukaemia (ALL) induction treatment. However, the implications of IM in subsequent ALL therapy phases after achieving remission remain unknown. This study investigated the relationship between IM (measured by plasma citrulline and the chemokine CCL20) and the development of BSI and systemic inflammation (reflected by C‐reactive protein, CRP) in children with ALL during high‐dose methotrexate (HDMTX) treatment, an important part of ALL consolidation therapy. The study compared patients treated according to the NOPHO ALL 2008 protocol (n = 52) and the ALLTogether1 protocol (n = 42), both with identical HDMTX procedures but different scheduling. One week post‐HDMTX, citrulline dropped to median levels of 14.5 and 16.9 μM for patients treated according to the NOPHO ALL 2008 and ALLTogether1 protocols, respectively (p = 0.11). In a protocol and neutrophil count‐adjusted analysis, hypocitrullinaemia (<10 μmol/L) was associated with increased odds of BSI within 3 weeks from HDMTX (OR = 26.2, p = 0.0074). Patients treated according to the NOPHO ALL 2008 protocol exhibited increased mucosal‐ and systemic inflammation post‐HDMTX compared to patients treated according to ALLTogether1, with increased CCL20 (14.6 vs. 3.7 pg/mL, p < 0.0001) and CRP levels (10.0 vs. 1.0 mg/L, p < 0.0001). Both citrulline and CCL20 correlated with CRP for these patients (rs = −0.44, p = 0.0016 and rs = 0.35, p = 0.016, respectively). These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.

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Mucositis-associated bloodstream infections in adult haematology patients with fever during neutropenia: risk factors and the impact of mucositis severity

de Jonge,

Janssen,

Ypma

et al. 2024

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Purpose Haematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever. Methods This prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge. Results We included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia. Conclusion In haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI. Trial registration ClinicalTrials.gov (NCT02149329) at 19-NOV-2014.

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

Cited by 5 publications

References 61 publications

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

Intestinal mucositis, systemic inflammation and bloodstream infections following high‐dose methotrexate treatment in childhood acute lymphoblastic leukaemia: Comparison between the NOPHO ALL 2008 protocol and the ALLTogether1 protocol

Mucositis-associated bloodstream infections in adult haematology patients with fever during neutropenia: risk factors and the impact of mucositis severity

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