NIH trial success suggests a new treatment option for older, sicker patients

Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Healths Clinical Center in Bethesda, Maryland, by researchers from NIHs National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.

The transplant done in the study reversed sickle cell disease in nearly all the patients. Despite having both donor stem-cells and their own cells in their blood, the patients stopped the immunosuppressant medication without experiencing rejection or graft-versus-host disease, in which donor cells attack the recipient. Both are common, serious side effects of transplants.

Blood drawn from a sickle cell patient. Source: NIH Molecular and Clinical Hematology Branch

Typically, stem-cell recipients must take immunosuppressants all their lives, said Matthew Hsieh, M.D., lead author on the paper and staff clinician at NIH. That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen.

In sickle cell disease (SCD) sickle-shaped cells block blood flow. It can cause severe pain, organ damage and stroke. The only cure is a blood stem-cell, or bone marrow, transplant. The partial transplant performed in the study is much less toxic than the standard full transplant, which uses high doses of chemotherapy to kill all of the patients marrow before replacing it with donor marrow. Several patients in the study had less than half of their marrow replaced.

Immunosuppressant medication reduces immune system strength and can cause serious side effects such as infection and joint swelling. In this study, 15 of 30 adults stopped taking the medication under careful supervision one year after transplant and still had not experienced rejection or graft-versus-host disease at a median follow up of 3.4 years.

Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease, said John F. Tisdale, M.D., the papers senior author and a senior investigator at NIH. Not having to permanently rely on this medication, along with use of the relatively less-toxic partial stem-cell transplant, means that even older patients and those with severe sickle cell disease may be able to reverse their condition.

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