Genetic Susceptibility to Hepatic Sinusoidal Obstruction Syndrome in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

AbstractHepatic sinusoidal obstruction syndrome (SOS/VOD) represents a dramatic complication of hematopoietic stem cell transplantation (HSCT), particularly in children. Recent evidence has suggested a role for the gut microbiome (GM) in the context of HSCT and its related complications, but no data are available on the relationship between GM and SOS/VOD. Here, we conducted a retrospective case–control study in allo-HSCT pediatric patients developing or not SOS/VOD and profiled their GM over time, from before the transplant up to 72 days after. A rich and diverse GM before HSCT was found to be associated with a reduced likelihood of developing SOS/VOD. Furthermore, prior to transplant, patients not developing SOS/VOD showed an enrichment in some typically health-associated commensals, such as Bacteroides, Ruminococcaceae and Lachnospiraceae. Their levels remained overall higher until post-transplant. This high-diversity configuration resembles that described in other studies for other HSCT-related complications, including graft-versus-host disease, potentially representing a common protective GM feature against HSCT complications.

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Analysis of risk factors for hepatic sinusoidal obstruction syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03732-1 ◽

2021 ◽

Author(s):

Jaspar Kloehn ◽

Grit Brodt ◽

Jana Ernst ◽

Bernd Gruhn

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Gemtuzumab Ozogamicin ◽

Sinusoidal Obstruction Syndrome ◽

Hematopoietic Stem ◽

Hepatic Sinusoidal Obstruction Syndrome

Abstract Purpose Hepatic sinusoidal obstruction syndrome (SOS) represents a serious complication following hematopoietic stem cell transplantation (HSCT). Our study aimed to investigate important risk factors of SOS in a pediatric population. Methods This retrospective study analyzed 105 children, adolescents and young adults who underwent allogeneic HSCT at our pediatric HSCT center in Jena. The observation period was 12 years and SOS was defined by the pediatric criteria of the European Society for Blood and Marrow Transplantation (EBMT). Results 15 out of all 105 patients developed SOS (14.3%). The median time from HSCT to SOS diagnosis was 12 days. The mortality rate of SOS was 20.0%. In univariate analyses, we identified the significant risk factors of patient age < 1 year [odds ratio (OR) = 7.25, p = 0.037], prior treatment with gemtuzumab ozogamicin (OR = 11.00, p = 0.020), high pretransplant ferritin levels above 1500 ng/mL (OR = 4.00, p = 0.033), 2000 ng/mL (OR = 4.69, p = 0.016), and 2400 ng/mL (OR = 5.29, p = 0.005) as well as international normalized ratio (INR) ≥ 1.3 (OR = 5.91, p = 0.009). The following risk factors could be confirmed in multivariate analysis: treatment with gemtuzumab ozogamicin (OR = 9.24, p = 0.048), ferritin > 2400 ng/mL (OR = 5.74, p = 0.023), and INR ≥ 1.3 (OR = 8.02, p = 0.007). Conclusion Our study confirms several risk factors from the current literature. Additionally, this is the first report on the risk factor of high pretransplant INR.

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