Can Pre-Transplant Liver Fibrosis Predict Overall Survival Following Hematopoietic Stem Cell Transplantation for Patients with Sickle Cell Disease?
In a retrospective study presented at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, CA, researchers found a significant association between liver fibrosis and reduced overall survival among patients with sickle cell disease (SCD) who underwent hematopoietic stem cell transplantation (HCT).
Patients with SCD have an increased risk for liver fibrosis due to transfusional hemosiderosis, chronic hemolysis, and vaso-occlusive events. These patients are at greater risk for endothelial damage and transplant-related complications following HCT. Historically, patients with advanced liver disease, such as cirrhosis or active hepatitis are excluded from HCT trials, limiting data on the effects of liver fibrosis on transplant-related outcomes in this population.
In a retrospective study, researchers analyzed registry data from 1881 patients who underwent HCT for SCD between 1991 and 2021. Among them, 104 underwent liver biopsy pre-transplant, with 37 showing liver fibrosis. The median age of patients with fibrosis was 16 years of age, older than their counterparts without fibrosis who had a median age of 11 years. The study compared the survival outcomes and complications between these two groups. The study’s key endpoints included overall survival, event-free survival, and the incidence of graft-versus-host disease (GVHD), thrombotic microangiopathy (TMA), and veno-occlusive disease (VOD).
The study revealed a significant association between liver fibrosis and reduced overall survival. Patients with fibrosis had a mortality rate of 24.3% compared with 7.5% among those without fibrosis. Cox regression analysis confirmed that liver fibrosis independently increased the hazard of death (hazard ratio = 3.299), even after adjusting for age. Interestingly, the presence of liver fibrosis had no statistically significant effect on event-free survival or the incidence of transplant-related complications, such as acute or chronic GVHD, TMA, or VOD.
While these findings highlight a concerning association between liver fibrosis and poorer outcomes, the study faced limitations. These included a small sample size, lack of data on biopsy indications or fibrosis severity, and biases inherent to registry data. Still, the study authors believe these study results warrant future research.
“Pre-transplant liver fibrosis is an independent predictor of poorer overall survival in SCD patients undergoing HCT for SCD, irrespective of age,” the researchers concluded. “Future research examining the underlying the relationship between pre-HCT liver disease and outcomes of HCT for SCD and have the potential to inform strategies to prevent and treat transplant related toxicity.”
Reference
Maurya P, Liang J, Prior D, Ramachandran SP, Deng Y, Krishnamurti L. Pre-transplant liver fibrosis predicts poor overall survival following hematopoietic stem cell transplantation for sickle cell disease. Paper presented at: 66th ASH Annual Meeting & Exposition. San Diego, CA. December 7, 2024. https://ash.confex.com/ash/2024/webprogram/Paper211601.html.