A sad fact about bone-marrow transplants is that the chemotherapy used to kill the diseased cells and prevent rejection increases patients' risk of graft-versus-host
disease (GVHD). But new research suggests a way to avoid this serious
complication: by replenishing a natural antibiotic protein that's depleted when neutrophils are destroyed by chemotherapy. A multicenter clinical trial led by Children's and the Dana-Farber Cancer Institute is about to test this idea, using a recombinant form of the antibiotic, called bactericidal/permeability-increasing
protein (BPI).
Prior studies provide a strong rationale for trying BPI, says Ofer Levy, MD, PhD, in Children's Division of Infectious Diseases. In mice, chemotherapy damages the intestinal lining, allowing bacterial endotoxin to enter the bloodstream. The
endotoxin then provokes an inflammatory response that mobilizes donor immune cells, helping trigger GVHD. Blocking endotoxin reduced the incidence of GVHD in mice.
BPI, which Levy has studied for years, is a natural endotoxin blocker.
Reporting at the American Society of Hematology meeting in December, Levy and Eva Guinan, MD, of Dana-Farber and Children's Division of Hematology/
Oncology, showed that patients undergoing chemotherapy and bone-marrow
transplants not only have a marked post-transplant rise in endotoxin, but also a sharp drop in BPI—just when they need it most. GVHD risk was greater in the
BPI-deficient patients.
If initial safety tests go well, Levy and Guinan will lead a randomized, controlled trial of BPI in 30 to 40 patients undergoing bone-marrow transplants for cancer or blood diseases. Unlike other treatments to prevent GVHD, BPI doesn't suppress the immune system and has shown virtually no toxicity to date.
