Allogeneic hematopoietic stem-cell transplant protocol successful in adult sickle cell disease

A protocol that combines allogeneic hematopoietic stem cell transplantation with total-body irradiation and treatment with alemtuzumab and sirolimus allowed for the successful reversal of the sickle cell phenotype in adults with the disease.

The protocol was tested in a phase-1/2 study. Ten adults with severe sickle cell disease underwent nonmyeloablative transplantation with CD34+ peripheral-blood stem cells. Each patient’s donor underwent several days of granulocyte colony-stimulating factor mobilization. In addition to the transplantation, the researchers tested a conditioning regimen.

As part of the conditioning regimen, patients received 1 mg/kg of alemtuzumab, a humanized monoclonal antibody directed against CD52, in increasing doses on days seven and three prior to transplant. A single dose of 300 cGy of total body irradiation on day two and oral sirolimus starting the day before transplant was also given.

Patients have been followed for a median of 30 months. At that time, all ten patients were alive; graft was retained in nine patients.

Mean donor-recipient chimerism for T cells was 53.5%; mean percentage of circulating donor myeloid cells was 83.3%.

Most importantly, no acute or chronic graft-versus-host disease developed in any of the patients.

“We believe that our results are due to the conditioning regimen. Total-body irradiation at a dose of 300 cGy must have created enough bone marrow space to allow a degree of hematopoiesis from donor stem cells that was sufficient to reverse the sickle cell disease phenotype,” the researchers wrote. “In addition, this level of radiation supplements the immunosuppression required to prevent rejection of the allograft.”

Hsieh MM. N Engl J Med. 2009;361:2309-2317.