Sickle Cell Disease Potentially Cured with Nonmyeloablative HLA-Matched Allogeneic Stem Cell Transplantation

John F. Tisdale, MDMedicalResearch.com Interview with:
Dr. John Tisdale MD
Molecular and Clinical Hematology Branch
National Institute of Diabetes and Digestive and Kidney Diseases,
National Heart, Lung, and Blood Institute, Bethesda, Maryland


MedicalResearch: What are the main findings of the study?

Dr. Tisdale: Using a nonmyeloablative allogeneic HLA-match peripheral blood stem cell transplantation strategy aimed at tolerance induction, we were able to revert the phenotype in 26 of 30 adult patients with severe sickle cell disease ranging in age from 16 to 65 years. In contrast to standard transplantation strategies which rely on high doses of chemo and/or radiotherapy after which the entire bone marrow and blood system is replaced by that of the donor, our patients had a mixture of their own and that of their donor. This procedure was well tolerated, with no non-relapse mortality, and led to complete replacement of red blood cells by that of the donor in successfully engrafted patients. This replacement resulted in decreases in pain, pain medication usage, hospitalizations, and improvements in organ function.


MedicalResearch: Were any of the findings unexpected?

Dr. Tisdale: There were two unexpected, but welcome findings in the study.

  • The first was the absence of graft-versus-host disease, a very common complication of bone marrow transplantation in which the immune cells of the donor attack the skin and organs of the patient. This complication can be severe, even fatal, but was not observed in any of our patients.
  • The second unexpected finding was that despite our patients having a mixture of both donor and patient cells in the bone marrow and blood termed mixed chimerism, we were able to successfully stop immunosuppression medication in more than half of the successfully engrafted patients with continued stable mixed chimerism.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Tisdale: Clinicians should consider nonmyeloablative allogeneic HLA-matched peripheral blood stem cell transplantation in adults with severe sickle cell disease and should incorporate a discussion of this potentially curative option into their care.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Tisdale: Future research in this area should include extension of this potentially curative approach to half-matched family members, and such studies are currently underway.

Citation:

Nonmyeloablative HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Phenotype

Last Updated on August 23, 2014 by Marie Benz MD FAAD