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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 56; no. 5; pp. 1021 - 1030
• Main Authors: Ebbesen, Maria, Weischendorff, Sarah, Kielsen, Katrine, Kammersgaard, Marte, Juul, Anders, Müller, Klaus Gottlob
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2021; Nature Publishing Group
• Subjects: 631/250/1904; 631/532/1542; 692/499; Anti-inflammatory agents; Biomarkers; Bone marrow; C-reactive protein; Cardiovascular diseases; Care and treatment; Cell Biology; Children; Complications; Criteria; Cytotoxicity; Damage; Diseases; Endothelial cells; Endothelium; Growth factors; Health aspects; Hematology; Hematopoietic stem cells; Hyperbilirubinemia; Inflammation; Insulin; Insulin-like growth factor I; Insulin-like growth factors; Internal Medicine; Intestine; Medicine; Medicine & Public Health; Mucosa; Pediatrics; Public Health; Risk factors; Sine waves; Stem cell transplantation; Stem Cells; Transplantation; Transplants & implants; Denmark
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-020-01127-3

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.