Short-term erythrocytapheresis is associated with resolution of vertebral osteonecrosis in children with sickle cell disease

Abstract Introduction: Chronic erythrocytapheresis or red cell exchange transfusion therapy (RCE) is used to maintain low hemoglobin S levels to treat both acute and chronic complications of sickle cell disease (SCD). This therapeutic modality is used indefinitely in children at high risk of developing stroke and/or secondary prophylaxis for stroke prevention. However, the short-term benefits of this treatment have not been evaluated in children. In this study, we analyzed the impact of short-term RCE transfusion on end-organ function in pediatric SCD patients. Methods We retrospectively analyzed data from SCD cohort of Central California - from the initiation of RCE to 2 years after commencement of program. REDCap data extraction was done on demographic, hematologic, pulmonary, liver and renal function data at baseline (pre), and at 0.5, 1, and 2 years of RCE therapy (post). MRI images of all patients with identified osteonecrosis (ON) at baseline and post-therapy were compared. Statistical analysis was performed using paired t-tests to compare pre- and post-treatment values. The percentage change in mean values was determined by comparing mean values from pre-treatment and post-treatment period. Results The study included a total of 171 children with sickle cell disease in the Central California Cohort - Black or African American (n=134), White (n= 19), Asian (n=3), Bi-racial (n=3), and Unknown or Other (n=12). There was nearly equivalent male (n=85) and female (n=86) distribution.Ethnic distribution included Hispanic or Latino (n=22),Not Hispanic or Latino (n=136), and Unknown (n=5). Among the entire cohort, 58 were taking hydroxyurea (HU) and 6 were on other disease-modifying treatments. Of these subjects, five children were eligible for RCE due to stroke, stenosis of cerebral arteries or elevated transcranial doppler ultrasound velocities. All 5 children were previously on HU. Using Terumo Optia Apheresis system and the Single-needle technique, RCE was conducted in 5 individuals with a target goal of Hemoglobin S and Hemoglobin SC (S + C) <30%, using a fraction of cell remaining (FCR) of 30- 50%. The average time interval between RCE was 4.6 weeks and the number of packed red blood cell (pRBC) units for RCE were 3- 7 per person per session (Mean of 5.2 pRBC units/person). For the five patients who received RCE, estimated glomerular filtration rate (eGFR) following treatment decreased from mean values of 144 mL/min/1.73m² to 112.9 mL/min/1.73m² (p< 0.05) six months post-treatment. Significant improvements in Hemoglobin A levels and reductions in Hemoglobin S levels were observed (p < 0.05). Ferritin levels also decreased from a mean of 1341.36 ng/mL pre-treatment to 626.52 ng/mL post-treatment (p=0.093). No significant difference was observed in liver, cardiac and pulmonary function during this period. Three children ON of the vertebrae showed improvement during the observation period. Acute changes associated with ON showed resolution in 1 patient with multifocal vertebral infarctions on magnetic resonance imaging (MRI) at 2 year post-RCE. Improvement in backpain and quality of life were noted in all subjects without physical therapy and surgical intervention. One child had an allo-antibody, Anti-Jkb, detected prior to initiation of RCE. No new alloantibodies were detected in these children during RCE. There were no admissions for pain crises during this period of observation. However, one child had a PowerFlow port-associated line sepsis and needed admission to the hospital for antibiotic therapy and removal and replacement of the port. Conclusion We observed a significant alteration in eGFR following short-term RCE. Our results also demonstrate improvement in ON and resolution of symptoms following RCE. This seems to be a promising non-surgical treatment modality for patients with vertebral ON. Further prospective studies are needed to analyze the clinical impact of short-term exchange transfusion on ON and bone health in sickle cell disease.