Under the direction of Dr. Walters, the Blood and Marrow Transplant Program offers transplantation using allogeneic and autologous stem cell donations to benefit children with cancer or blood disorders. Particular attention is paid to blood and marrow transplantation for children with β–thalassemia major and sickle cell disease, including innovative research, under Walters direction, to reduce complications after transplantation for patients with these diseases. Clinical investigations to study the role of sibling donor and unrelated donor umbilical cord blood transplantation for hemoglobinopathies also are under way.
Walters is leading efforts to conduct long-term follow up evaluations in an NIH-sponsored multi-center cooperative study of bone marrow transplantation (BMT) for sickle cell disease (SCD). These data are being compared to outcomes observed in the natural history of sickle cell disease, as reported by the Cooperative Study of Sickle Cell Disease (CSSCD). This comparison will be very important in helping clinicians determine who and when to consider transplantation for SCD. There is also an ongoing clinical trial to explore the possibility of performing transplantation with less intensive, non-myeloablative pre-transplantation therapy. This approach, performed in the clinic, aims to establish a condition termed stable mixed chimerism whereby tolerance to donor and host cells is maintained. Initial results in this clinical trial suggested that additional intensive immunosuppression was required to ensure stable donor engraftment, and a revised protocol was adopted which is currently enrolling patients. Another strategy that might expand the availability of transplantation is to utilize unrelated donors or donors who are not fully histocompatible. We are exploring novel methods that might promote donor tolerance and prevent graft-versus-host disease without impairing engraftment, a problem that has been observed after applying conventional methods of T-cell depletion to the stem cell graft. Encouraging results of pre-clinical studies in mice and dogs will be translated into a clinical trial in the near future. Finally, we are attempting to learn more about the cellular and molecular events associated with graft rejection when it occurs after transplantation for hemoglobinopathies. To do so, we are performing evaluations of cellular immune tolerance and microarray profiling of gene expression in individuals who are enrolled in our currently active trials so that we might identify patients at risk for this important complication and institute appropriate preventive therapy. These clinical investigations are closely linked to the HLA, genomic core, and RBC biology laboratories at CHORI and represent concerted efforts by CHORI investigators to develop new therapies for individuals who inherit clinically significant hemoglobinopathies.
For information regarding clinical trials in the Blood and Marrow Transplant Program, please click here.