Chemotherapy-free transplant approach for sickle cell disease - Children's National

For children with sickle cell disease (SCD), a stem cell transplant from a matched sibling donor can offer a cure, but the intensive chemotherapy traditionally used before transplant can cause significant short- and long-term side effects.

A new multicenter clinical trial led by Children's National and published in Blood Advances points to a potentially safer path forward. Researchers evaluated a regimen that avoids chemotherapy and found it was feasible, well tolerated and did not result in graft-versus-host disease (GVHD), one of transplantation's most serious complications.

While additional work is needed to improve long-term transplant success, the findings mark an important step toward safer curative therapy for children with SCD.

Why it matters

For decades, chemotherapy has been considered an essential part of preparing patients for stem cell transplant. While effective, it can carry risks ranging from short-term illness to long-term health complications.

This study challenges this long-standing approach by showing that a matched sibling donor transplant may be possible without chemotherapy. Researchers also found that no patients developed GVHD, a potentially life-threatening complication in which donor immune cells attack the patient's body.

The study also captured how patients were feeling in the weeks after transplant, offering an early look at the patient experience during recovery.

"One of the most exciting findings was that patients' reported quality of life did not decline in the early period after transplant," Robert Nickel, MD, study author and pediatric hematologist at Children's National, said. "That is noteworthy because we typically expect patients to experience significant side effects and a temporary worsening in how they feel during the weeks immediately following transplant.""

Moving the field forward

Researchers found that approximately one in five patients experienced graft rejection, causing SCD to return.

The ongoing trial has been modified to improve donor cell engraftment while preserving the regimen's favorable safety profile.

The next phase will focus on strengthening long-term transplant success.

"Our goal is to make curative therapy for sickle cell disease safer without compromising its effectiveness," said Dr. Nickel. "These results show that a chemotherapy-free transplant is possible and help us understand how to improve engraftment so more children can benefit."

Children's National leads the way

Children's National led the international multicenter trial and enrolled the largest number of patients. The study is among the first to evaluate this approach in children with SCD - an option not currently available at most pediatric transplant centers.

The research was supported by the Doris Duke Foundation.

Read the full study, "Nonmyeloablative HLA-identical sibling transplant for sickle cell disease in children: a multicenter prospective study," in Blood Advances.

Additional Children's National authors include Allistair Abraham, MD, Steven J. Hardy, PhD, Maryanne Odinakachukwu, Julia Malloy, and Anqing Zhang, PhD.