Undergoing Stem Cell Transplant for Sickle Cell Disease in Childhood

Transplant recipients show better physical, school, and social functioning than those receiving transfusions and medications alone

LBA-5: Outcome of Cerebral Vasculopathy and Cognitive Performances 10 Years Post-Enrollment in the Drepagreffe Trial Comparing Allogeneic Stem Cell Transplantation to Standard-Care in Children with Sickle Cell Anemia and History of Abnormal Cerebral Velocities

(SAN DIEGO—Dec. 10, 2024) – Children who received a stem cell transplant for sickle cell disease (SCD) experienced better quality of life outcomes and cognitive performance 10 years after their transplant compared with children who received chronic transfusion therapy and the SCD drug hydroxyurea but did not undergo a stem cell transplant. This is according to new study results presented during the 66th American Society of Hematology (ASH) Annual Meeting and Exposition.

The findings reflect 10-year outcomes from the DREPAGREFFE-1 trial, which ran from 2010-2013 in France, and was the first head-to-head comparison of allogeneic stem cell transplantation versus standard of care for children with SCD. Combined with the study’s one-year and three-year outcomes, the 10-year findings further strengthen the evidence in favor of stem cell transplantation for reducing complications and improving the overall outlook for people living with SCD, according to the researchers.

“This trial demonstrated that following stem cell transplantation, patients had a better quality of life, not only for physical functioning but also for social and school functioning,” said the study’s lead author, Françoise Bernaudin, MD, a physician at Hôpital Intercommunal de Créteil, Université Paris-Est, in France. “We found that these patients can have a greater ability to do sports and run, attained higher academic degrees, are not anxious about their future, and experience less anger and less difficulty with memory compared with those who received chronic transfusions and hydroxyurea.”

SCD is an inherited blood disorder that causes red blood cells to become sickle-shaped, impeding the flow of blood and reducing the ability for blood to carry oxygen to tissues and organs. This results in episodes of acute pain as well as long-term damage, causing a range of complications throughout life and increasing the risk of premature death. One common SCD complication is abnormally high cerebral arterial velocities, an indicator of stenosis presence or reduced oxygen delivery to the brain, which can be associated with a greater risk of strokes and cognitive problems.

DREPAGREFFE-1 enrolled 67 children between ages five to 15 who were receiving chronic blood transfusions to prevent complications from abnormal cerebral arterial velocities. Those with a matched sibling donor (n=32) were transplanted while those without a matched sibling donor (n=35) continued their transfusions and then switched to hydroxyurea in absence of stenosis and if their cerebral arterial velocities normalized. At one and three years, those who received a stem cell transplant showed significant improvements in several measures compared with those who did not receive a transplant, but at those timepoints there was no difference in the presence of ischemic lesions (blood clots that block blood flow in the brain) or cognitive performance.

In the subsequent years, researchers continued to follow up with study participants, including through clinical evaluations, brain scans, and tools for assessing quality of life and cognitive functioning.

At 10 years, quality of life scores related to physical, school, and social functioning were significantly higher among those who received a stem cell transplant. For cognitive performance, participants who received a stem cell transplant showed significantly better performance on tests used to assess working memory and processing speed. There was no difference between groups in terms of verbal comprehension, perceptual reasoning, or emotional quality of life scores.

The researchers also assessed trends in the rate of silent cerebral infarcts (SCIs) – a type of small stroke that is visible on a brain scan but causes no obvious symptoms. While it is unclear whether SCIs influence cognitive functioning, they are considered to be a sign of increased SCD severity and complications. SCIs were found in 18 participants at the time of enrollment; at 10 years, five additional patients had developed silent cerebral infarcts in the standard-of-care arm compared to zero in the stem cell transplant arm.

Taken together, researchers said that the study findings suggest that undergoing stem cell transplantation results in better outcomes for children with SCD compared with chronic transfusions and hydroxyurea. While this can offer additional reassurance for patients, families, and physicians who are considering the procedure, Dr. Bernaudin noted that families should also be aware of the risks of undergoing a stem cell transplant, including infertility, which is a common side effect of the conditioning regimen used to clear the bone marrow in preparation to receive a transplant.

She said that fertility preservation procedures are available in France for all patients undergoing stem cell transplantation for SCD at no charge to the families, adding, “with this technique, we hope that the patients will be able to have children after the transplantation.”

Looking ahead, Dr. Bernaudin said that it would be useful to compare outcomes from haplo-identical stem cell transplant to gene therapy, a type of treatment that has become more widely available since DREPAGREFFE-1 was conducted. She also noted that additional work is needed to further improve transplantation techniques to minimize the risk of complications or treatment failure particularly after haplo-identical transplants in children.

This study was sponsored by the Centre Hospitalier Intercommunal de Créteil (CHIC Hospital) in France and was funded by the Agence de Biomédecine and Pfizer.

Françoise Bernaudin, MD, Hôpital Intercommunal de Créteil, Université Paris-Est, will discuss this study in the Late-Breaking Abstracts session on Tuesday, December 10, 2024, at 7:30 a.m. Pacific time in Hall B (San Diego Convention Center).

About the American Society of Hematology

The American Society of Hematology (ASH) (hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. Since 1958, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology.

The Blood journals (https://ashpublications.org/journals) are the premier source for basic, translational, and clinical hematological research. The Blood journals publish more peer-reviewed hematology research than any other academic journals worldwide.

Claire Whetzel, 202-629-5085
cwhetzel@hematology.org