Haematopoietic stem cell transplantation improves stroke risk in children with sickle cell anaemia

Matched sibling donor stem cell transplantation (MSD-HSCT) was associated with lower transcranial doppler velocities (TCDs) at 1 year compared with chronic transfusions. Furthermore, MSD-HSCT was also associated with changes in highest TCDs at 3 years, normalisation rate at 1 year, and ferritin levels at 1 and 3 years [1].

In the late-breaking plenary session, Dr Francoise Bernaudin (Intercommunal Hospital Center de Créteil, France) presented their study data showing that increased TCD in children with sickle cell anaemia (SCA) is associated with an increased risk of ischaemic stroke, stenosis, and silent cerebral infarcts. Previous studies have identified the pivotal role of chronic transfusions in reducing stroke risk, while newer studies have considered other preventive approaches such as hydroxyurea or MSD-HSCT. The DREPAGREFFE study is a nonrandomised, controlled, open-label intervention study that was conducted at 9 sites in France [2].

A total of 67 children were enrolled with 32 assigned to the transplantation group and 35 to the standard care group. Study visits were completed at baseline, 1 year, and 3 years. Primary outcome consisted of time-averaged mean of maximum velocities (TAMV) without angle correction in the 8 cerebral arteries at 1 year. A total of 29 secondary outcomes were utilised in the study that included highest TAMV at 1 and 3 years, incidence of ischaemic stroke, and survival without ischaemic stroke.

In the transplantation group, highest TCDs were significantly lower on average at 1 year (129.6 cm/s vs 170.4 cm/s; P<0.001). Similarly, highest TCDs at 3 years were lower in the transplantation group (112.4 cm/s in transplantation group vs 156.7 cm/s in standard of care; P=0.001). Normalisation at 1 year was higher in the transplantation group (80.0% in transplantation group vs 48.0% in standard of care; P<0.05). Ferritin levels were lower in the transplantation group at 1 year (905 ng/mL in transplantation group vs 2,529 ng/mL in standard of care group; P<0.05) and 3 years (382 ng/mL in transplantation group vs 2,170 ng/mL in standard of care group; P<0.05).

The post-hoc analysis strongly supported the conclusion that in children who had not experienced a stroke, stenosis of the Circle of Willis, a known predictor of stroke, was significantly reduced in children who had received a stem cell transplantation (P<0.01).

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   1. Bernaudin F, et al. Abstract LB2605, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.
   2. Bernaudin F, et al. JAMA. 2019 Jan 22;321(3):266-276.

Posted on 9 August 201917 May 2024