Approximately 50 to 60 percent of adults who receive an allogeneic stem cell transplant experience a complication called chronic graft-versus-host disease (GVHD) that occurs because of the genetic differences between the patient and the donor stem cells. In essence, the donor cells recognize the recipient's own cells as foreign and react by trying to attack and destroy the cells in the patient's body, causing debilitating and sometimes life-threatening symptoms such as skin rashes, blisters, joint pain, stiffness, dry mouth, and dry eyes.

Chronic GVHD is the leading cause of mortality among people who survive two or more years following a stem cell transplant, and currently there are no effective treatment options to aid in preventing this complication.

Recent research has indicated that dysregulation of B cells, a type of white blood cell that produces antibodies to fight infection, may play a role in the development of chronic GVHD. Studies have shown that rituximab, a monoclonal antibody that works by depleting B cells, may play a role in the treatment of the condition. The purpose of this exploratory phase II study was to determine if the use of rituximab following an allogeneic stem cell transplant could help prevent chronic GVHD.

Researchers from the Dana-Farber Cancer Institute in Boston enrolled a total of 64 patients who were in remission following an allogeneic stem cell transplant to receive rituximab once every three months for one year (three, six, nine, and 12 months post-transplant). The primary endpoint of the study was to determine the incidence of steroid-requiring chronic GVHD at one year following an allogeneic stem cell transplant. Historically, researchers at Dana-Farber have found that 60 percent of all cases of chronic GVHD require treatment with corticosteroids within one year following transplant. However, treatment with corticosteroids is not optimal as these therapies are known to cause severe and unfavorable side effects.

To date, a total of 54 patients have been evaluated at 12 months after receiving all prescribed courses of rituximab. The study found that the cumulative incidence of any chronic GVHD was 44.6 percent with only 31.2 percent of patients requiring treatment with corticosteroids. Additionally, only 22.4 percent of patients were on corticosteroids at 12 months, and 50 percent were able to discontinue immunosuppressant therapy. Relapse-free survival was 71.1 percent, and overall survival was 88.6 percent.

"Results of this study indicate that rituximab is a promising therapy for the prevention of chronic graft-versus-host disease following an allogeneic stem cell transplant," said lead study author Corey Cutler, MD, MPH, FRCPC, Assistant Professor of Medicine, Harvard Medical School and Dana-Farber Cancer Institute in Boston. "It appears that the use of rituximab may reduce the need to use corticosteroids by up to 50 percent when compared with what we have used historically. However, these results need to be confirmed in a larger randomized clinical trial."


Source: ASH