, suggesting that this intervention may improve outcomes related to cerebral vasculopathy.
Matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) was linked to significantly lower transcranial Doppler (TCD) velocities at one year compared to standard care in the 9-center study, investigators reported in JAMA.
The study enrolled children with sickle cell anemia who required chronic transfusion due to persistently high TCD velocities, which are associated with increased stroke risk, researchers said.
“Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up,” said the researchers, led by Françoise Bernaudin, MD, of Centre Hospitalier Intercommunal de Créteil, Créteil, France
In the non-randomized, prospective DREPAGREFFE study by Dr. Bernaudin and colleagues, 32 children with sickle cell anemia who had a matched sibling donor underwent transplantation, while another 35 children received standard therapy. The primary end point of the study was time-averaged mean of maximum velocities (TAMV) in cerebral arteries at one year.
The highest TAMV at one year was on average 129.6 cm/s in the MSD-HSCT group, versus 170.4 cm/s in the standard care group, for a difference of -40.8 cm/s (P less than .001), Dr. Bernaudin and co-investigators reported.
The improvement persisted at 3 years, with a TAMV of 112.4 cm/s in the transplantation group and 156.7 cm/s in the standard care group (P less than .001), which they also reported as a secondary outcome of the study.
These findings indicate that MSD-HSCT may allow patients with a history of abnormal TCD velocities to stop transfusions and hydroxyurea, Dr. Bernaudin and colleagues said.
The improvement in TCD velocities may be due in part to anemia correction, but also to the “exclusive presence” of normal red blood cells following transplantation, as opposed to simultaneous presence of normal and sickled cells as would be seen after transfusion, they added.
This study wasn’t powered to determine whether a 40 cm/s reduction in TCD velocities would translate into clinical benefits such as reduction in stenosis and silent infarct, or improved cognitive function, they said. Even so, there were no infarcts or stenoses in the MSD-HSCT group, whereas those event occurred in 9% and 6% of patients in the standard care group, respectively, they added.
Dr. Bernaudin reported disclosures related to Addmedica and bluebird bio. Co-authors reported disclosures with Addmedica, Novartis, Alexion, Amgen, Jazz Pharmaceuticals, and others.
SOURCE: Bernaudin F, et al. JAMA. 2019;321(3):266-276.