A multicenter, phase II study published in Blood found that bone marrow transplantation with unrelated donor marrow resulted in high rates of one-year event-free survival (EFS) and overall survival (OS) in children with severe sickle cell disease (SCD); however, the authors also observed a high incidence of graft-versus-host disease (GVHD), which may make it inappropriate for widespread adoption.
The authors assessed the safety and efficacy of bone marrow grafts from unrelated adult donors in 30 children with a median age of 14 years (range = 6-19 years; 53% were boys). All of the patients received a conditioning regimen consisting of alemtuzumab, fludarabine, and melphalan.
The median follow-up was 26 months (range = 12-62 months). Rate of EFS at one year (the study’s primary endpoint) was 76 percent (95% CI 56-88), and OS was 86 percent (95% CI 67-95). At two years, EFS was 69 percent (95% CI 48-82) and OS was 79 percent (95% CI 59-90).
At 100 days post-transplant, the cumulative incidence of grade 2-4 acute GVHD was 28 percent (95% CI 13-45) and of grade 3/4 acute GVHD was 17 percent (95% CI 6-33). After one year, the cumulative incidence of chronic GVHD was 62 percent (95% CI 41-77); the authors classified 38 percent of these cases as “extensive.” Eight patients died, and seven of these deaths were related to GVHD complications.
“The GVHD rates were higher than those seen after matched, unrelated donor transplantation in other disorders,” said lead author Shalini Shenoy, MD, professor of pediatrics at Washington University School of Medicine and director of the pediatric stem cell transplant program at St. Louis Children’s Hospital. “We believe this is multifactorial, and may be related to race or ethnicity, patient age among recipients who developed GVHD, the design of the conditioning regimen used to target engraftment, or the inflammatory nature of SCD itself.”
Sources: Shenoy S, Eapen M, Panepinto JA, et al. A BMT CTN phase II trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood. 2016 September 13. [Epub ahead of print]