Elevated plasma CXCL9 and CHI3L1 prior to HCT predict post-HCT lung complications in children.
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OBJECTIVES: Lung complications occur commonly post-haematopoietic stem cell transplant (HCT) in children and contribute significantly to mortality. The development of biomarkers predictive of post-HCT lung complications may improve outcomes for these children. Therefore, the primary objective of this study was to identify pre-transplant plasma biomarkers predictive of lung complications in children undergoing HCT. METHODS: Plasma samples from 117 pre-HCT patients were used to measure 78 soluble immune analytes, and extensive clinical metadata were retrospectively collected from the electronic medical record, including clinical characteristics of the post-HCT lung complications. RESULTS: Firstly, we showed that the plasma cytokine signature of children undergoing HCT differed significantly between children depending on the indication for HCT (malignant vs non-malignant). Secondly, we found that the plasma cytokine signature changed with the age of the patient. Thirdly, we showed that elevated pre-HCT plasma levels of CXCL9 and Chitinase 3-like 1, both induced by IFN-γ, were predictive of post-HCT lung complications in patients with a malignant indication for HCT [area under the curve (AUC): 0.70, P = 0.0007 and AUC: 0.68, P = 0.0016, respectively]. CONCLUSION: In conclusion, we have identified two potential biomarkers of post-HCT lung disease in paediatric patients and these require validation in future cohorts.