Transplant outperforms standard care for children with sickle cell
10-year follow-up reveals fewer pain crises and better cognitive development
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Children with sickle cell anemia, the most common and severe form of sickle cell disease (SCD), who undergo stem cell transplant experience better long-term cognitive function after a decade than those given standard treatments like hydroxyurea or blood transfusions, according to a 10-year follow-up study.
Transplant recipients also generally report fewer hospitalizations, fewer pain crises, and an overall better quality of life.
The study, “Better 10-Year Cerebrovascular Outcome After Transplant Than on Standard-Care in Sickle Cell Anemia: DREPAGREFFE Trial,” was published in the American Journal of Hematology.
SCD is a genetic disorder marked by an abnormal form of hemoglobin, the protein that red blood cells use to carry oxygen through the body. The abnormal hemoglobin causes red blood cells to take on a sickle shape, making them more prone to destruction and to block blood vessels, which can cause painful vaso-occlussive crises (VOCs).
This blockage of blood vessels can also occur in the brain, increasing the risk of stroke, especially in pediatric patients. This risk increases as blood flow velocity in the brain rises.
Comparing transplant to standard care
In the early 2010s, a group of scientists in France conducted a clinical study, called DREPAGREFFE-1 (NCT01340404). The trial tested the effects of stem cell transplant versus standard-of-care treatment with hydroxyurea or blood transfusions in children with sickle cell anemia who had abnormally high brain blood flow velocities.
A stem cell transplant, also called a bone marrow transplant, involves replacing a patient’s hematopoietic stem cells (which make new blood cells) with those from a healthy donor, allowing the body to produce new red blood cells without the defective version of hemoglobin. Although this procedure carries risks, it can cure the disease.
Hydroxyurea (sold as Siklos and Xromi) is an oral medication approved to reduce the frequency of pain crises and the need for blood transfusions in people with sickle cell anemia.
In the study, 32 children underwent stem cell transplant from a sibling-matched donor, while another 35 received standard-of-care treatment. Results reported several years ago showed that stem cell transplantation outperformed standard care on several outcomes, including reductions in brain blood flow velocity and improvements in quality-of-life measures related to physical and school functioning.
No significant differences were detected between groups in cognitive function measures at that time. However, the results covered only three years of follow-up, and the researchers wondered whether a difference would emerge with longer follow-up.
To find out, the same scientists conducted another study 10 years later, called DREPAGREFFE-2 (NCT05053932), in which they reassessed the 67 children who had participated in the original study. The mean age at the follow-up assessment was 18 years in the transplant group and 19.2 years in the standard-of-care group.
Long-term safety outcomes were broadly consistent with earlier data: no deaths or new strokes were reported after the study’s start, and none of the children who had undergone stem cell transplant experienced later rejection of the transplant.
Still, most girls who underwent stem cell transplant did not spontaneously undergo puberty without medical assistance. The researchers noted that issues with fertility and hormonal states remain an important consideration when weighing the benefits and risks of a stem cell transplant. This approach typically involves pre-treatment with chemotherapy agents to kill all of the person’s hematopoietic cells to make room for the transplanted, healthy cells.
Better quality of life and reduced hospitalizations
Over the course of a decade, children who had undergone stem cell transplant had significantly lower rates of hospitalizations and VOCs compared with their peers receiving hydroxyurea or blood transfusions.
In line with the original study’s results, long-term data indicated that stem cell transplantation led to significantly greater reductions in brain blood flow velocity and stenosis (narrowing of blood vessels in the brain). Scores related to quality of life were also generally better in the transplant group.
“The present trial demonstrates that [stem cell transplant] patients experienced significantly fewer hospitalizations and crises than those on [blood transfusions] or hydroxyurea, resulting in improved [quality of life], and most likely, in a drastic reduction in costs,” the researchers wrote.
They added that those in the transplant group “had significantly less difficulties engaging in sport, less pain, feeling less anger, experiencing greater ability to do more activities, being less forgetful, and missing less school or work because [of] not feeling well.”
Unlike the original study, the long-term follow-up found significant group differences in cognitive function. In general, cognitive scores tended to worsen slightly in the year immediately following the stem cell transplant, but improved over the next several years of follow-up.
In contrast, cognitive scores of participants on standard care improved in the first years of the study, but then worsened over longer follow-up.
“These findings support recommending [stem cell transplant] before the age of 15 in children with symptomatic [sickle cell anemia and available match-sibling donor] to preserve cognitive functions, enabling them to realize their social and professional dreams,” the researchers concluded.
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