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Grading bloodstream infection risk using citrulline as a biomarker of intestinal mucositis in patients receiving intensive therapy

Bone Marrow Transplantation volume 57, pages 1373–1381 (2022)Cite this article

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Abstract

Earlier studies have suggested that severe intestinal mucositis (IM; citrulline < 10 µmol/L) is an independent risk factor for bloodstream infections (BSI) after cytotoxic therapy. Our aim was to grade IM in patients receiving commonly used chemotherapy and conditioning regimens, and characterize its relationship with BSI incidence. In a retrospective analysis of remission induction (RI) chemotherapy, or conditioning for autologous and allogeneic hematopoietic stem cell transplantation (HSCT; myeloablative conditioning [MAC] and non-myeloablative and reduced-intensity conditioning [NMA/RIC]), data were collected on central venous catheter (CVC) characteristics and BSI. The relationship between BSI occurrence and the degree of IM (determined by citrulline levels) and neutropenia was analyzed. In 626 CVC episodes, 268 (42.8%) laboratory-confirmed BSIs (LCBIs) occurred, classified as mucosal barrier injury (MBI)-LCBIs in 179 (28.6%) episodes, central line–associated BSIs in 113 (18.1%) episodes, and catheter-related BSIs in 55 (8.8%) episodes. In NMA/RIC, the mean duration of hypocitrullinemia was 0.77 days, with LCBI and MBI-LCBI occurring in 11.1% and 4.8% of episodes. In autologous HSCT, RI, and MAC allogeneic HSCT, LCBI and MBI-LCBI occurred frequently (40.0–63.8% and 22.8–53.2% of episodes, respectively) and the mean duration of hypocitrullinemia was significantly higher (9.2–13.8 days). There was a strong correlation between LCBI and the duration of hypocitrullinemia (Pearson’s correlation coefficient R = 0.96), as opposed to the relationship between LCBI and the duration of neutropenia (R = 0.42). We conclude that citrulline can be used to grade BSI risk for commonly used intensive treatment regimens.

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Fig. 1: Citrulline concentrations over time after the start of chemotherapy.
Fig. 2: Summary of the citrulline concentrations over time for all treatment regimens.
Fig. 3: Time to occurrence of bacteremia.
Fig. 4: Correlation between LCBI, citrulline, and neutropenia.

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Authors and Affiliations

  1. Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

    C. E. M. de Mooij, W. J. F. M. van der Velden, S. Fazel, L. F. J. van Groningen & N. M. A. Blijlevens

  2. Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

    C. E. M. de Mooij, W. J. F. M. van der Velden, L. F. J. van Groningen & N. M. A. Blijlevens

  3. Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands

    A. F. J. de Haan

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Contributions

CEMM, WJFMV and NMAB designed the study. SF maintained the CVC registry. CEMM, AFJH, LFJG and WJFMV analyzed and interpreted the data. AFJH and CEMM performed the statistical analysis. CEMM, WJFMV and NMAB wrote the manuscript. All authors critically revised and approved the final manuscript.

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Correspondence to C. E. M. de Mooij.

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de Mooij, C.E.M., van der Velden, W.J.F.M., de Haan, A.F.J. et al. Grading bloodstream infection risk using citrulline as a biomarker of intestinal mucositis in patients receiving intensive therapy. Bone Marrow Transplant 57, 1373–1381 (2022). https://doi.org/10.1038/s41409-022-01719-1

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