Better 10‐Year Cerebrovascular Outcome After Transplant Than on Standard‐Care in Sickle Cell Anemia: DREPAGREFFE Trial

ABSTRACT Management of cerebral vasculopathy in sickle cell anemia (SCA) includes standard‐care, that is, chronic transfusion (CT) or hydroxyurea, and hematopoietic cell transplantation (HCT). DREPAGREFFE‐1 (December 2010/June 2013), a French multicenter trial, was the first prospective trial comparing standard‐care to match sibling donor (MSD)‐HCT in 67 (35F/32M) SCA children (5–15 year) on CT for abnormal time‐averaged mean maximum velocities (TAMMV ≥ 200 cm/s). Seven had a stroke history. We reported that MSD‐HCT reduced the highest TAMMVs at 1‐ and 3‐year ( p < 0.001) and improved quality of life (QoL) for physical and school functioning. In stroke‐free patients, the 3‐year stenosis score was lower ( p = 0.010). Nevertheless, no significant difference was observed for silent cerebral infarcts (SCI) and cognitive performance. This prompted us to initiate DREPAGREFFE‐2 to reevaluate the outcomes at 10 years (September 2022/August 2024) with the same 67 SCA children. No death or stroke occurred in either arm. No rejection or chronic‐GvHD arose in the MSD‐HCT group ( n = 32). In the standard‐care group ( n = 35), 16 were on hydroxyurea, and 16 on CT at Year 10, and 3 received haploidentical‐HCT. After MSD‐HCT, the QoL was better, even for social functioning, and the number of hospitalizations, hospitalized days ( p < 0.001), and crises ( p = 0.001) was lower than on standard‐care. In stroke‐free patients, stenosis ( p = 0.027) and SCI scores ( p = 0.041) decreased significantly more after MSD‐HCT than on standard‐care; working memory ( p = 0.016) and processing speed ( p = 0.011) improved significantly after MSD‐HCT, but worsened on standard‐care. These effects were not previously detected with shorter follow‐up. This supports earlier consideration of HCT for SCA children with MSD to preserve neurologic function and QoL for a more productive future.