Pre-Transplant Liver Fibrosis Predicts Poor Overall Survival Following Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

Background: Hematopoietic stem cell transplantation (HCT) is a curative treatment for SCD. Patients with sickle cell disease (SCD) are at increased risk of liver fibrosis due to transfusional hemosiderosis, chronic hemolysis, and vaso-occlusive events. Patients are at high risk for endothelial damage and transplant related complications following HCT. Cirrhosis, bridging fibrosis, and active hepatitis are generally considered exclusion criteria for enrolment in clinical trials of HCT for SCD. There is a paucity of data on the outcomes of HCT in patients with SCD who were found to have liver fibrosis pre-HCT.

Objective: To determine the transplant outcomes of patients with SCD found to have fibrosis on liver biopsy pre-transplant.

Methods: We undertook a retrospective registry-based study including 1881 patients who had undergone HCT for SCD from 1991 to 2021 with data submitted to Center for International Blood and Marrow Transplant Research (CIBMTR). A total of 104 patients underwent liver biopsy prior to transplant for evaluation of fibrosis. The mean age of patients who underwent liver biopsy was 15.53 (± 10.15) years, with 49% female, and 88% African American. Among these, 37 patients had pre-transplant liver fibrosis. Cox proportional hazards regression models were used to assess the impact of pre-transplant liver fibrosis on various outcomes, including liver fibrosis and age at transplant as covariates. Key outcomes were overall survival, event free survival, acute and chronic graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and thrombotic microangiopathy (TMA). No data were available on the why the patients underwent liver biopsy, whether patients had transfusional hemosiderosis or what was the degree of fibrosis.

Results: Of the 37 patients who were found to have fibrosis 28 were over the age of 10 years with a median age of 16.0 (2.0 – 44.0) years as opposed to 11.0 (3.0 – 44.0) amongst those without fibrosis( p=0.037). There were no statistically significant differences in demographics, pre-HCT disease characteristics, donor or graft type, conditioning, GVHD prophylaxis, and indication for HCT between patients who with fibrosis and without. Overall, 14 of 104 ( 13.5%) patients who underwent liver biopsy died post HCT, including 9 of 37 (24.32% ) died with fibrosis and 5 of 67 (7.5%) without fibrosis. Cox regression analysis showed that the presence of fibrosis was associated with increased hazards of death (HR = 3.299, 95% CI [1.115, 10.921]) for overall survival, independent of age. This presence of fibrosis had no statistically significant association with event free survival, incidence of acute GVHD, chronic GVHD, TMA or VOD. The analyses are however limited by the small sample size, lack of detail on indication for liver biopsy, grading of liver fibrosis, and sources of bias inherent to registry data, but serve as a rational for further study of the impact of liver fibrosis on outcomes of HCT for SCD.

Conclusions: Pre-transplant liver fibrosis is an independent predictor of poorer overall survival in SCD patients undergoing HCT for SCD, irrespective of age. 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.

Disclosures: No relevant conflicts of interest to declare.

See more of: 904. Outcomes Research: Hemoglobinopathies: Poster I
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