Posterior Reversible Encephalopathy in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant for Hemoglobinopathies: A Multicenter Retrospective Database Study

Abstract

Introduction It is unknown if improvements in supportive care have altered the risk of calcineurin inhibitor (CNI) mediated posterior reversible encephalopathy syndrome (PRES) in patients with hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia major. We conducted a multicenter retrospective study to determine prevalence of PRES and associated risk factors in a contemporary cohort of patients with hemoglobinopathies transplanted at US children's hospitals. Methods The Pediatric Health Information Systems database, an administrative database containing information from 49 pediatric hospitals, was used to extract data on eligible patients who underwent allogeneic hematopoietic cell transplant (HCT) from 2003 to 2017. Outcomes were compared between SCD and β-thalassemia cohorts and analyzed using non-parametric methods. Results 788 patients (586 SCD, 202 β-thalassemia) were included (Table 1). PRES was seen in 8.1% (n=64) of the cohort with greater prevalence in SCD than β-thalassemia patients (9.7% vs 3.4%; p=0.005). All patients received CNI therapy post-HCT. Hypertension (HTN) pre-HCT, iron overload, use of unrelated donors, fludarabine-based regimen and corticosteroid therapy post-HCT were significant risk factors in SCD cohort only. In both cohorts, increasing age and graft versus host disease (GvHD) were significant risk factors but not neurological deficits pre-HCT, sex, and graft source. One-year-mortality was increased in PRES affected SCD vs unaffected patients (19% vs 5% p=0.0002) but not in β-thalassemia patients with PRES vs without (29% vs 9% p=0.133) Conclusion In our study, prevalence of PRES was higher in SCD than β-thalassemia patients. Studies evaluating CNI- free regimens are needed to abrogate the risk of PRES in this high-risk population.