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Hemoglobinopathy

Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin

Bone Marrow Transplantation volume 35, pages 171–177 (2005)Cite this article

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.

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Acknowledgements

We are grateful for the kind and thoughtful advice provided by the advisory panel members Dorothy Moore (New Jersey Medical School) and Phyllis Bazen (Upstate Medical University and Executive Director of the Syracuse Sickle Cell Association). We also thank those advisory panel members who served on the adjudication committee: Mary Jane Petruzzi, Children's Hospital of Buffalo; Stephan Dubansky, Upstate Medical University; Norma Lerner, University of Rochester; Sharon Space, Boston University; Charles Packman, Carolinas Medical Center; Maala Varma, New Jersey Medical School. This work was supported by grants from the Genzyme Corporation, the Strong Children's Research Center and the National Institute's of Health grant no. HL 68091.

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Authors and Affiliations

  1. Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    J T Horan

  2. Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    J L Liesveld & P Fenton

  3. Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    N Blumberg

  4. Children's Hospital and Research Center of Oakland, Oakland, CA, USA

    M C Walters

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  1. J T Horan
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  2. J L Liesveld
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Correspondence to J T Horan.

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Horan, J., Liesveld, J., Fenton, P. et al. Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. Bone Marrow Transplant 35, 171–177 (2005). https://doi.org/10.1038/sj.bmt.1704745

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