Blood Rheology After Allogeneic Hematopoietic Stem Cell Transplantation or Gene Therapy in Sickle Cell Disease

Allogeneic hematopoietic cell transplantation (HCT) and autologous hematopoietic stem cell-based gene therapies are potentially curative for sickle cell disease (SCD). Although most patients experience resolution of overt clinical symptoms associated with SCD with donor-dominant myeloid chimerism after undergoing HCT or the induction of a substantial amount of alternative hemoglobin after gene therapy, whether the underlying subclinical physiology is normalized in these individuals is unknown. One approach to evaluating the underlying physiology is to characterize the blood rheology of patients after they receive these therapies. We assessed the rheology of 123 blood samples from 69 patients, of whom 43 underwent HCT (32 from matched related donors, 11 from haploidentical donors) and 11 received gene therapy. The results were compared to those for patients treated with hydroxyurea with optimum fetal hemoglobin response (HUOptimum) (n = 15). Median rheology parameters of recipients of HCT from donors with sickle cell trait (HbAS) were superior to those of gene therapy recipients (elongation index minimum [EImin]: 0.6 vs 0.31; point of sickling [PoS]: 0 vs 26.21) and of the HUOptimum cohort (EImin: 0.6 vs 0.15; PoS: 0 vs 36.2: percentage of dense red blood cells [%DRBC]: 0.9 vs 4.9) (P < 0.05 for all comparisons). Results for the gene therapy and HUOptimum groups were comparable (P > 0.05). Given the substantial number of patients with abnormal rheology and the associations between rheology and SCD-related complications, rheology tests may be included in the follow-up care for HCT and gene therapy recipients.