Sustained improvement in sickle cell cardiomyopathy after haematopoietic stem cell transplantation is superior to that with disease-modifying therapy.

Allogeneic haematopoietic stem cell transplantation (HSCT) is curative for sickle cell disease (SCD) - a group of inherited haemoglobin disorders encompassing homozygous haemoglobin S (HbSS) and compound heterozygous sickling disorders, including haemoglobin SC disease (HbSC), haemoglobin S/β0-thalassaemia (HbSβ0), haemoglobin S/β+-thalassaemia (HbSβ+), etc., but its long-term impact on SCD myocardial remodelling is incompletely characterized. We performed serial cardiac magnetic resonance imaging (CMR) and echocardiography in children and young adults with SCD undergoing matched-sibling or haploidentical HSCT in a prospective clinical trial with up to 36 months of post-HSCT follow-up. CMR assessments were conducted before HSCT and through the post-HSCT period. Echocardiographic parameters at 12 months post HSCT were compared with those of age-matched participants receiving disease-modifying therapies (DMTs). Among 20 HSCT recipients (mean age 14.8 years), CMR demonstrated progressive reductions in biventricular volumes and left atrial volume over 36 months, with preservation of ejection fraction. Extra-cellular volume, a surrogate marker of myocardial fibrosis, showed significant improvement from baseline, having normalized in nearly all participants assessed at 36 months. Compared with age-matched DMT recipients, HSCT recipients had lower tricuspid regurgitant jet velocity and improved diastolic parameters at 12 months post-HSCT, with normalization of cardiac output on echocardiography. These findings demonstrate sustained reversal of myocardial fibrosis and structural cardiac remodelling after HSCT for SCD. HSCT may, therefore, modify the trajectory of SCD cardiomyopathy beyond the improvements achieved with current DMTs.