In children, graft‑versus‑host disease (GVHD) can be a severe complication of allogeneic hematopoietic stem cell transplantation. Patients with steroid‑refractory acute GVHD (SR‑aGVHD) often have high mortality rates because treatments have offered limited efficacy and significant toxicity. However, the recent FDA approval of mesenchymal stromal cell (MSC) therapy for pediatric patients aged 2 months and older with SR‑aGVHD represents a major clinical milestone grounded in clinical trial evidence led by Joanne Kurtzberg, MD, and Kris M. Mahadeo, MD, PhD, clinician researchers and bone marrow transplant specialists at Duke Children’s.

Mahadeo explains that two patients have been treated with MSC therapy at Duke Children’s since FDA approval, “but we’ve been administering this therapy for many years with clinical trials.”

The FDA approval of MSC therapy for pediatric patients was based on data from a phase 3, prospective single-arm multicenter study evaluating children with primary SR-aGVHD, led by Kurtzberg and supported by Mahadeo. The MSC product with remestemcel-L significantly improved the overall response rate at day 28 in approximately 70% of treated pediatric patients, with the response sustaining through day 100. Early response also translated into improved survival; overall survival was 74.1% at day 100 and 68.5% at day 180. 

“The results of this study showed that this treatment is effective and very well tolerated by pediatric patients, who experienced no infusion-related toxicities, infections, or safety concerns,” says Mahadeo. “This evidence was central to FDA approval as a novel first-line therapy in pediatric patients with graft versus host disease and steroid resistance.”

“Mesenchymal stromal cells have immunomodulatory effects without further suppressing immune function,” says Mahadeo. Unlike steroids, MSC therapy calms immune dysregulation as a result of both the bone marrow transplant and resulting GVHD. “It doesn’t hinder immune cells or suppress the immune system like steroids do,” he adds. While steroids are still the first-line standard of care treatment for GVHD, MSC therapy may have expanded indications in the future. 

MSC therapy does not require donor‑recipient matching and is administered intravenously. Mahadeo adds, “We can administer this therapy rather quickly. It can often be given outpatient, usually two times per week for four weeks, helping some patients avoid hospitalization and recover from GVHD in the comfort of their home and with their families.”

While GVHD affects each child differently, manifestations of severe skin rashes, gastrointestinal distress, and/or liver dysfunction can significantly affect the quality of life and function of a child. “If a child is resistant to steroid therapy, they previously didn’t have a good option to stop GVHD and reverse its potentially debilitating effects. Now, they do. This treatment can help a small subset of children in a big way,” Mahadeo says.

Delivering MSC therapy requires specialized expertise, coordination, and infrastructure. Centers offering this treatment, like Duke Children’s, have dedicated pediatric transplant teams, experience managing severe GVHD, and established protocols for administering cell‑based therapies safely. 

“Our stem cell lab is Foundation for the Accreditation of Cellular Therapy (FACT) accredited, meeting qualifications to receive and produce stem cell products. Our clinical staff is also trained and experienced with administering these products through our infusion protocols. It takes a dedicated team, which we have at Duke, to deliver these advanced therapies and provide the best care to patients,” concludes Mahadeo.