High Survival Rates for SCD Patients with Groundbreaking Transplant Approach
A bone marrow transplant strategy that avoids high-dose chemotherapy to prevent an immune reaction against donor stem cells has demonstrated high rates of event-free and overall survival in sickle cell disease (SCD) patients, according to a Phase 2 clinical trial. This innovative approach includes a non-myeloablative pre-transplant conditioning regimen, which effectively prepares the body for the new cells without eliminating all existing stem cells, reducing the risk of donor cell rejection, especially in adult recipients.
Two years after transplant, the event-free survival rate — the proportion of patients living without graft failure — neared 83%, while the overall survival rate was an impressive 94%, as reported by the researchers. While eight out of thirty-two children experienced graft failures, no such cases were observed in the thirty-eight adults participating in the trial.
Furthermore, this regimen is less expensive and simpler to manage compared to traditional myeloablative gene therapy and gene editing techniques. This cost-efficiency suggests its potential as a viable treatment option for resource-limited regions, including many African countries.
The study, titled “An International Learning Collaborative Phase 2 Trial for Haploidentical Bone Marrow Transplant in Sickle Cell Disease,” was published by a global team of researchers in the journal Blood.
The study enrolled 70 children and adults diagnosed with SCD across North America, Europe, and Asia. The median age was 19.1, and the majority (95.6%) received a transplant from a parent or sibling. Graft failure occurred in eight patients (11.4%), all under 18 years of age.
“No adult participants were excluded due to stroke or severe pre-existing heart, lung, and kidney disease,” the scientists highlighted.
Researchers anticipated that at least 80% of patients would survive without graft rejection within two years post-transplant. The actual event-free survival rate was 82.6% at two years, with an overall survival rate of 94.1%. There was no significant difference between children and adults.
Most patients experienced successful engraftment, where transplanted stem cells survived and proliferated within the bone marrow. Out of 59 individuals with full engraftment, 57 (96.6%) discontinued immunosuppressive medications one year after the transplant.
Complications included severe acute graft-versus-host disease in about 10% of patients one year post-transplant, with no distinction between children and adults (12.5% and 7.9%). Approximately the same proportion experienced moderate or severe chronic graft-versus-host disease after two years of follow-up. Five patients (7.1%) passed away due to infections.
“To our knowledge, we conducted the first multicentre, international phase 2 trial of a non-myeloablative haploidentical BTM using thiotepa and PTCy to treat children and adults with SCD,” the researchers stated. They believe this approach is readily accessible for SCD patients in middle- and high-income countries and emerging availability in Africa, where over 70% of the world’s children with SCD are born.
This bone marrow transplant method and conditioning regimen have become a therapeutic curative option for adults with SCD in middle-high income BMT centers, the researchers concluded.
