In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation.

Stable, mixed donor-recipient chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with sickle cell disease (SCD) is sufficient for phenotypic disease reversal and results from differences in donor/recipient red blood cell (RBC) survival. Understanding variability and predictors of RBC survival among patients with SCD before and after HSCT is critical for gene therapy research which seeks to generate sufficient corrected hemoglobin to reduce polymerization thereby overcoming the red cell pathology of SCD. This study utilized biotin-labeling of RBCs to determine the lifespan of RBCs in patients with SCD compared to patients who have successfully undergone curative HSCT, participants with sickle cell trait (HbAS), and healthy (HbAA) donors (NCT04476277). Twenty participants were included in the analysis (N=6 SCD pre-HSCT, N=5 SCD post-HSCT, N=6 HbAS, N=3 HbAA). The average RBC lifespan was significantly shorter for participants with SCD pre-HSCT (64.1 days, range 35-91) compared to those with SCD post-HSCT (113.4 days, range 105-119), HbAS (126.0 days, range 119-147), and HbAA (123.7 days, range 91-147) (p<0.001). RBC lifespan correlated with various hematologic parameters, and strongly correlated with the average final fraction of sickled RBCs after deoxygenation (p<0.001). No adverse events were attributable to the use of biotin and related procedures. Biotin labeling of RBCs is a safe and feasible methodology to evaluate RBC survival in patients with SCD before and after HSCT. Understanding differences in RBC survival may ultimately guide gene therapy protocols to determine hemoglobin composition required to reverse the SCD phenotype as it relates directly to RBC survival.

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