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. 2024 Oct 8;13(19):5991.
doi: 10.3390/jcm13195991.

Early Fever in Allogeneic Stem Cell Transplantation: Are Presepsin and YKL-40 Valuable Diagnostic Tools?

Jakša Babel  1 , Iva Košuta  1 , Ana Vujaklija Brajković  1   2 , Ana Lončar Vrančić  3 , Vedran Premužić  4 , Dunja Rogić  3   5 , Nadira Duraković  2   6
Affiliations

Early Fever in Allogeneic Stem Cell Transplantation: Are Presepsin and YKL-40 Valuable Diagnostic Tools?

Jakša Babel et al. J Clin Med. .

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510-0.802) and Day 3 (AUC 0.698; 95% CI: 0.559-0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572-0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 μg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

Keywords: YKL-40 protein; bone marrow transplantation; chitinase-3-like protein 1; hematopoietic stem cell transplantation; human; presepsin protein; procalcitonin.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Serum values of PSP, YKL-40, and PCT during the first seven days after the onset of FE. Values are plotted on a linear scale after natural logarithm transformation due to their wide range, allowing better visualization. (a) Differences in median LnPSP concentrations. (b) Differences in median LnYKL-40 concentrations. (c) Differences in median LnPCT concentrations. Each box-and-whiskers plot (drawn using the Tuckey method) depicts the median value (horizontal line) and the values from the first to third quartile (central box). Each whisker extends from the edges of the box to the smallest and largest values within 1.5 times the interquartile range. Outliers are depicted as circles. Differences in biomarker values between FUO and infection groups were tested using the Mann–Whitney U test. ns = non-significant, * = p < 0.05, ** = p < 0.01. FE, febrile episode; FUO, fever of unknown origin; PCT, procalcitonin; PSP, presepsin.
Figure 1
Figure 1
Serum values of PSP, YKL-40, and PCT during the first seven days after the onset of FE. Values are plotted on a linear scale after natural logarithm transformation due to their wide range, allowing better visualization. (a) Differences in median LnPSP concentrations. (b) Differences in median LnYKL-40 concentrations. (c) Differences in median LnPCT concentrations. Each box-and-whiskers plot (drawn using the Tuckey method) depicts the median value (horizontal line) and the values from the first to third quartile (central box). Each whisker extends from the edges of the box to the smallest and largest values within 1.5 times the interquartile range. Outliers are depicted as circles. Differences in biomarker values between FUO and infection groups were tested using the Mann–Whitney U test. ns = non-significant, * = p < 0.05, ** = p < 0.01. FE, febrile episode; FUO, fever of unknown origin; PCT, procalcitonin; PSP, presepsin.
Figure 2
Figure 2
Differences in biomarker median concentrations in FUO and the infection group across Day 0, Day 1, Day 3, Day 5, and Day 7 time points. (a) Differences in median PSP concentrations. (b) Differences in median YKL-40 concentrations. (c) Differences in median PCT concentrations. Results are shown as median values with interquartile range. All values for PCT Day 0 in both groups were below the detection limit (<0.6 μg/L). To ensure a conservative estimate and clinical relevance, for statistical analysis, the values were substituted with the detection limit of 0.6 μg/L. Adjusted p value: * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001. FUO, fever of unknown origin; PCT, procalcitonin; PSP, presepsin.
Figure 3
Figure 3
Receiver operating characteristic (ROC) curve analysis data for PSP, YKL-40, and PCT serum concentrations to differentiate infectious from non-infectious causes of fever at (a) Day 1, (b) Day 3, (c) Day 5, and (d) Day 7 after the onset of fever. For details on AUC p-values, please see Table 5. AUC, area under the ROC curve; PCT, procalcitonin; PSP, presepsin.
Figure 4
Figure 4
Best multivariable logistic regression models showing odds ratio for infection for PSP and PCT on (a) Day 1 and (b) Day 3. The black circles represent the estimated odds ratio, and the horizontal red lines with whiskers show the 95% confidence interval. An odds ratio greater than 1 indicates an increased likelihood of infection. * = p < 0.05.
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