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Transplant Toxicities

Associations between levels of insulin-like growth factor 1 and sinusoidal obstruction syndrome after allogeneic haematopoietic stem cell transplantation

Abstract

Allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) is challenged by severe adverse events, as cytotoxic effects of the conditioning may result in systemic inflammation, leaky epithelial barriers and organ toxicities, contributing to treatment-related morbidity and mortality. We hypothesised that insulin-like growth factor-1 (IGF-1), a mediator of growth and proliferation of various tissues, may attenuate chemotherapy-induced tissue damage after HSCT. We prospectively measured plasma levels of IGF-1 and its binding protein 3 (IGFBP-3) in 41 patients undergoing myeloablative HSCT. IGF-1 and IGFBP-3 levels were inversely correlated with C-reactive protein and interleukin-6 levels post HSCT. In multivariate analyses, low levels of IGF-1 and IGFBP-3 before conditioning were associated with increased risk of developing sinusoidal obstruction syndrome (SOS; OR=5.00 per 1 SDS decrease in IGF-1 (95% CI: 1.45–16.67), P=0.011 and OR=5.00 (1.37–20.00), P=0.015, respectively). Furthermore, low pre-transplant levels of IGF-1 and IGFBP-3 were associated with increased fluid retention during the first 21 days post transplant (OR=7.69 (95% CI: 1.59–33.33), P=0.012, and OR=2.94 (1.03–8.33), P=0.045). These data suggest that high levels of IGF-1 and IGFBP-3 may have a protective effect against fluid retention and SOS, possibly by attenuating systemic inflammation, and may prove useful as predictive biomarkers of SOS.

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Acknowledgements

Financial support was obtained from The Danish Cancer Association and the Dagmar Marshall Foundation.

Author contributions

SW contributed to data collection, performed the statistical analyses and interpretation and drafted the manuscript. KK contributed to project design, data collection and data interpretation. HS, KJ, CHN and AJ participated in data collection. AJ, AEP and LPR contributed to project design. KGM designed the project, established the collaboration and contributed to data interpretation. All authors critically revised the manuscript and gave their final approval of the version to be published.

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Correspondence to S Weischendorff.

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Weischendorff, S., Kielsen, K., Sengeløv, H. et al. Associations between levels of insulin-like growth factor 1 and sinusoidal obstruction syndrome after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 52, 863–869 (2017). https://doi.org/10.1038/bmt.2017.43

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