Preventing graft-versus-host disease disease after bone marrow transplant -- without toxicity

Unless the donor is an identical twin, patients undergoing bone-marrow transplant (also known as hematopoietic stem cell transplant, or HSCT) must first receive powerful chemotherapy drugs to wipe out their immune system and prevent their bodies from rejecting the donated cells. Research from Childrens Hospital Boston and the Dana-Farber Cancer Institute has helped demonstrate that this punishing regimen increases the risk of graft-versus-host disease (GVHD), in which the donors cells mount an immune response against the patient. But the most recent findings also suggest that the risk for GVHD can be reduced by replacing a natural antibiotic protein, known as bactericidal/permeability increasing protein (BPI), which is depleted when patients undergo chemotherapy.

Now, a multicenter study is about to test this idea in HSCT patients, using a manufactured form of BPI known as rBPI21 (XOMA Ltd.) Unlike other treatments to prevent GVHD, BPI does not suppress the immune system and has shown virtually no toxicity.

Researchers Ofer Levy, MD, PhD, of Childrens Hospital Boston, and Eva Guinan, MD, of Childrens Hospital Boston and Dana-Farber Cancer Institute, will present their most recent findings and discuss the new clinical trial on December 11 at the American Society of Hematology (ASH) Annual Meeting in Orlando, Fla. (abstract # 2856).

The new trial is the culmination of over five years of collaborative research by Levy and Guinan in human patients. "Many basic and translational studies, including our own, have provided a strong rationale for a trial of BPI in patients undergoing hematopoietic stem cell transplants," says Levy. "Replenishing a natural host defense factor that is deficient due to chemotherapy makes theoretical and practical sense, and we hope that bringing our bench work to patients will reduce the complications they suffer."

GVHD occurs when immune cells from donor attack the recipient, and can lead to multiple

Contact: Anna Gonski
Children's Hospital Boston

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