U.S. Department of Health and Human Services

Potential New Treatment Option for Adults with Sickle Cell Disease

A new blood stem-cell transplant regimen effectively reversed sickle cell disease in 26 of 30 adult participants and allowed them to achieve stable mixed donor chimerism, a condition in which a person has two genetically distinct cell types in the blood.  Also of importance, 15 of the 30 adults were able to stop taking immunosuppressant medications 1 year after transplantation. In sickle cell disease, sickle-shaped red blood cells block blood flow.  The blockage can cause severe pain, organ damage, and stroke.  Mature red blood cells arise from stem cells.  Transplantation of blood stem cells, obtained from bone marrow or another source such as umbilical cord blood, has been used to cure children with severe disease.  However, the medical procedures used for preparing patients for transplantation have thus far been too toxic to be used in adults.

In this new regimen, instead of using chemotherapy to destroy the person’s bone marrow before infusing donor stem cells—as in the standard, prohibitively toxic procedure—the researchers used a low dose of radiation combined with two immunosuppressive drugs.  This type of procedure is referred to as “non-myeloablative,” meaning that it does not destroy the person’s own bone marrow.  Rather, it is thought to create “space” for the donor stem cells to successfully engraft.  After undergoing the non-myeloablative procedure, the participants, who all had severe sickle cell disease, were infused with peripheral blood stem cells from healthy sibling donors.  The researchers reported that the partial stem cell transplantation regimen effectively reversed sickle cell disease in the majority of adult participants, and half were able to stop immunosuppressant medications.  These medications are typically given to transplant recipients to prevent the immune system from rejecting the transplanted donor cells and to prevent donor cells from attacking the recipient (graft-vs-host disease).  However, immunosuppressant medications reduce immune system strength and can cause serious side effects such as infection and joint swelling.  The researchers reported that no graft-vs-host disease has been detected in patients after stopping immunosuppression medications at a median follow-up of 3.4 years.

This study represents an important advance to make a potentially transformative treatment available to a wider range of people, especially those who could not tolerate a standard stem cell transplant or long-term use of immunosuppressant medications.

Hsieh MM, Courtney D, Fitzhugh MD, Weitzel RP, Link ME, Coles WA, Zhao X, Rodgers GP, Powell JD, and Tisdale JF. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. JAMA 312: 48-56, 2014.