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Insulin-like growth factor-I predicts sinusoidal obstruction syndrome following pediatric hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 56, pages 1021–1030 (2021)Cite this article

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Abstract

Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT) initiated through damage of sinusoidal endothelium and inflammation. Insulin-like growth factor-l (IGF-l) maintains and repairs endothelium and intestinal mucosa. We hypothesized that low IGF-l levels may increase the risk of inflammatory complications, such as SOS, in HSCT-patients. We prospectively measured IGF-l concentrations in 121 pediatric patients before, during, and after allogeneic HSCT. Overall, IGF-l levels were significantly reduced compared with healthy sex- and age-matched children. IGF-I levels pre-HSCT and at day 0 were inversely associated with C-reactive protein levels, hyperbilirubinemia, and number of platelet transfusions within the first 21 days post-transplant. Low levels of IGF-I before conditioning and at day of transplant were associated with increased risk of SOS diagnosed by the modified Seattle criteria (pre-HSCT: OR = 1.7 (95% CI: 1.2–2.6, p = 0.01), and the pediatric EBMT criteria (pre-HSCT: 1.7 (1.2–2.5, p = 0.009) and day 0: 1.7 (1.3–2.5, p = 0.001)/SDS decrease in IGF-1). These data suggest that IGF-I is protective against cytotoxic damage and SOS, most likely through trophic effects on endothelial cells and anti-inflammatory properties, and may prove useful as a predictive biomarker of SOS.

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Fig. 1: IGF-I and IGFBP-3 plasma levels as sex- and age-adjusted SD-scores during pediatric HSCT from before conditioning until 21 days post transplant.
Fig. 2: Associations between IGF-I levels and CRP during the first three weeks post-HSCT.
Fig. 3: Associations between IGF-I levels and bilirubin during the first three weeks post-HSCT.
Fig. 4: IGF-I levels before conditioning until three weeks post-transplant according to a diagnosis of SOS.

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Acknowledgements

Financial support was obtained from The Research Council at Rigshospitalet and The Childhood Cancer Foundation (#2017–1997).

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Authors and Affiliations

  1. Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Maria Ebbesen, Sarah Weischendorff, Katrine Kielsen, Marte Kammersgaard & Klaus Gottlob Müller

  2. Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Katrine Kielsen, Marte Kammersgaard & Klaus Gottlob Müller

  3. Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Anders Juul

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Ebbesen, M., Weischendorff, S., Kielsen, K. et al. Insulin-like growth factor-I predicts sinusoidal obstruction syndrome following pediatric hematopoietic stem cell transplantation. Bone Marrow Transplant 56, 1021–1030 (2021). https://doi.org/10.1038/s41409-020-01127-3

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