Induction of Stable Chimerism for Sickle Cell Anemia

BACKGROUND:

Hematopoietic cell transplantation (HCT) has curative potential for individuals with sickle cell disease. While the results of conventional HCT have been good, this treatment carries risks of significant short- term and longterm toxicities. For this reason, HCT has been reserved for children who have experienced severe symptoms that predict a poor outcome. Of interest, some patients developed stable donor-host hematopoietic chimerism after conventional HCT. Due to a natural enrichment of donor erythrocytes in the blood, those who developed stable chimerism had a significant clinical benefit, even when there was a minority of donor cells. These observations have paralleled efforts to develop less-toxic, non-myeloablative preparative regiments for transplantation, proved first in a canine model of transplantation, and subsequently translated successfully in a clinical trial for older adults with hematological malignancies.

DESIGN NARRATIVE:

Multicenter open-label phase I-II study in 30 children with sickle cell disease that combines a non-myeloablative pre-transplant hematopoietic cell transplantation (HCT) therapy with modulated post-grafting immunosuppression to control host-versus-graft and graft-versus-host reactions. The approach relies on the ability to establish and maintain donor-host chimerism. The primary study endpoint is stable donor cell engraftment; secondary endpoints measure the impact of therapy on sickle cell-related symptoms and end-organ damage (disease-free survival, patient survival, graft-versus-host disease, complications etc). The trial will be conducted within the existing network of Comprehensive Sickle Cell Centers, and will be centrally coordinated by the Sickle Cell Coordinating Center.