From the Journals

Matched transplant improves stroke risk indicator in sickle cell anemia

 

Key clinical point: In children with sickle cell anemia, matched sibling donor hematopoietic stem cell transplants (HSCT) reduced an indicator of stroke risk, suggesting that the intervention may improve cerebrovascular outcomes.

Major finding: The primary end point, time-averaged mean of maximum velocities in cerebral arteries 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 (P less than .001).

Study details: A multicenter, non-randomized, prospective study (DREPAGREFFE) including 32 children with sickle cell anemia who underwent MSD-HSCT and 35 who received standard therapy.

Disclosures: Study authors provided disclosures related to Addmedica, bluebird bio, Novartis, Alexion, Amgen, Jazz Pharmaceuticals, and others.

Source: Bernaudin F, et al. JAMA. 2019;321(3):266-276.

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Promising results, but limited applicability

Results of DREPAGREFFE illustrate the benefits of matched sibling donor hematopoietic stem cell transplantation (HSCT) for a select group of children with sickle cell anemia, according to the author of an editorial on the study.

Matched sibling donor HSCT was well-tolerated in the study and linked to improved control of transcranial Doppler velocities compared to standard care, Janet L. Kwiatkowski, MD, said in the editorial.

“As a curative therapy, it also obviates the need for long-term treatment wrought with adherence challenges with the potential consequence of stroke, and morbidity from iron overload with transfusion therapy,” wrote Dr. Kwiatkowski.

Only a certain proportion of patients have matched sibling donor HSCT as a potential treatment choice, however, she added.

In this particular study, conducted at 9 sites in France, a higher-than-expected 48% of children with sickle cell anemia had a matched sibling donor, whereas in the United States, she said, less than 1 out of 5 such children would be expected to have an HLA-identical sibling donor.

Because many children don’t have an appropriate matched sibling donor, additional studies are needed not only to evaluate the role of HSCT using matched unrelated and haploidentical donors, Dr. Kwiatkowski said, but also to assess how gene therapy interventions impact cerebrovascular outcomes.

These comments are taken from the accompanying editorial in JAMA by Janet L. Kwiatkowski, MD, MSCE, of Children’s Hospital of Philadelphia, and the Department of Pediatrics at Perelman School of Medicine, University of Pennsylvania, Philadelphia. Dr. Kwiatowski disclosed relationships with bluebird bio, Apopharma, and Novartis.


 

FROM JAMA

In children with sickle cell anemia, matched sibling donor transplants improved an indicator of stroke risk in a multicenter French study, 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.

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