1. ¹Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
2. ²Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
3. ³Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
4. ⁴Children's Hospital and Research Center of Oakland, Oakland, CA, USA

Correspondence: Dr JT Horan, AFLAC Cancer Center and Blood Disorders Service, Blood and Marrow Transplant Program, 1405 Clifton Road NE, Atlanta, GA 30322, USA. E-mail: john.horan@choa.org

Received 22 July 2004; Accepted 14 September 2004; Published online 8 November 2004.

Abstract

Summary:

Patients with sickle cell disease (N=3) and thalassemia (N=1) with high-risk features received hematopoietic stem cell transplantations (HCT) to induce stable (full or partial) donor engraftment. Patients were 9–30 years of age. Fludarabine, rabbit anti-thymocyte globulin (ATG), and 200 cGy total body irradiation were administered pre-transplant. Patients received bone marrow (N=3) or peripheral blood stem cells (N=1) from HLA-identical siblings, followed by mycophenolate mofetil and cyclosporine for post-grafting immunosuppression. Significant lymphopenia, but only moderate neutropenia and thrombocytopenia developed post transplant. No grade IV nonhematological toxicities or acute graft-versus-host disease (GVHD) were observed. At 3 months after transplantation, three of four patients had evidence of donor myeloid chimerism (range, 15–100%). However, after post transplant immunosuppression was discontinued, graft rejection occurred in all but one patient. This patient is now doing well 27 months post transplant with full donor engraftment. One patient died after a second transplant, and another patient experienced a stroke as her graft was being rejected. These results suggest that stable donor engraftment after nonmyeloablative HCT is difficult to achieve among immunocompetent patients with hemoglobinopathies and that new approaches will need to be developed before wider application of this transplantation method for hemoglobinopathies.