Preservation of Organ Function after Transplantation for Sickle Cell Disease

Background Recipients of successful allogeneic hematopoietic stem cell transplant (HSCT) for sickle cell disease (SCD) have hemoglobin S levels that reflect those of the donor. SCD related organ damage targets vital organs and is variable based on age and disease severity, and can be further compromised by transplant related complications. Organ function parameters are generally not primary end-points for clinical trials but need longitudinal follow up. This study aims to describe organ function in transplant recipients followed for one or more years after HSCT for SCD. Methods Following Institutional Review Board approval, a retrospective chart review was undertaken of SCD patients >1-year from HSCT with donor engraftment. Demographic data and organ functions (lung, brain and eyes) pre, at one-year, and at most recent assessment were compared for each patient. Organ functions reviewed included, creatinine, brain imaging, intelligence quotient (IQ), pulmonary function, retinal examination, and ferritin levels. Results Twenty-two patients were included in this review. There were 10 matched sibling donor, 8 matched or mismatched unrelated donor, 1 haploidentical, and 3 cord blood transplant recipients. Four patients received repeat donor cell infusion for waning donor chimerism followed by stabilization. Median age at first HSCT was 10 years (range 4-21 years). Eleven patients had MRI changes pre-HSCT. At 1-year, 4 of 17 transplant recipients had new MRI changes (2 patients with PRES and 2 with worsening infarction). At last follow up 3 of 18 patients demonstrated new MRI changes: bilateral temporal mesial sclerosis (1) and silent infarcts (2). IQ testing was available both at baseline and anytime beyond 1 year in 7 patients. IQ improved or remained stable in 5 patients and was lower in 2 patients, but remained in the average range. Pulmonary function tests were available for 21 patients of which 4 patients had restrictive lung disease. Ferritin levels decreased in 13 of 18 patients beyond the first year post-HSCT. Ophthalmologic exams at baseline and after transplant were performed in 12 patients. While SCD retinopathy was detected at baseline in two patients, no retinopathy was noted after HSCT. Follow up is in progress for additional organs such as the heart and kidneys. Discussion Long-term follow up of SCD related parameters post-HSCT demonstrates the effect of the intervention on disease manifestations. Our data demonstrates stability or improvement in organ function in the majority of patients after HSCT. This retrospective analysis is limited by the lack of uniform assessment of SCD related parameters and by obstacles such as provider changes and insurance denials. Though our data indicates improvement in SCD parameters post-HSCT, it also underscores the importance of systematic follow up prospectively through clinical trials and registries following curative therapy for SCD.