Key Points Cardiac morphology improves significantly as early as 3 months after HSCT for SCD; these changes are maintained up to 1 year. Diastolic dysfunction is associated with mortality, and this study shows improvements in diastolic measures and other functional parameters.

Lawal et al report on a 45-fold increase in secondary hematologic malignancy in 120 patients following hematopoietic stem cell transplantation (HSCT) for sickle cell disease (SCD), comparable to what has been reported following gene therapy. Notably, the cohort is enriched for older patients and for haploidentical transplant recipients with mixed chimerism following HSCT. These data further support the idea that pre-existing premalignant myeloid clones undergo clonal selection in the setting of nonmyeloablative HSCT and contribute to secondary malignancy.

Hematopoietic stem cell transplantation (HSCT) is potentially curative in patients with sickle cell disease (SCD). Patients with stable donor engraftment after allogeneic HSCT are generally reported to not experience SCD-related complications; however, there are no published data specifically reporting the change in vaso-occlusive events (VOE) after HSCT. Data regarding the number of VOEs requiring medical attention in the 2 years prior to allogeneic HSCT were compared to the number of VOEs in the 2 years (0-12 months and 12-24 months) after allogeneic HSCT in patients with SCD. One-hundred sixty-three patients with SCD underwent allogeneic HSCT between 2005-2019. The average age at the time of HSCT was 21 years (range 7 months - 64 years). Most patients underwent non-myeloablative conditioning [75% (N=123)] and with a matched sibling donor [72% (N=118)]. The mean number of VOEs was reduced from 5.6 (range 0-52) in the 2 years prior to HSCT to 0.9 (range 0-12) in the 2 years post-HSCT(p<0.001). Of the post-HSCT events, VOE was more frequent during the first 12 months [0.8 (range 0-12)] compared to months 12-24 post-HSCT [0.1 (range 0-8)](p<0.001). In patients who had graft rejection (12%, N=20), VOEs were reduced from 6.6 (range 0-24) before HSCT to 1.1 (range 0-6) and 0.8 (range 0-8) in the 0-12 months and 12-24 months after HSCT, respectively (p<0.001). VOEs requiring medical care are significantly reduced after allogeneic HSCT for patients with SCD. These data should inform the results of newer autologous HSCT gene therapy approaches.