A Brief History of the Brief History of Low-Dose Transplants

Extract

There have been few steps forward in the realm of allogeneic transplants since their inception as a treatment for leukemia more than 30 years ago. Stepwise advances have widened the pool of potential donors for each patient, nudged downward the incidence of graft-versus-host disease, and gone a long way toward eliminating post-transplant viral infections, once a major problem.

Despite this progress, allogeneic transplants are still like “playing Russian roulette. There’s a pretty fair chance you’ll die from it,” said Robert Collins, M.D., director of bone marrow transplantation at the University of Texas Southwestern Medical Center, Dallas.

So a few years back when researchers from three major cancer centers began touting less toxic transplants that would leave patients’ bodies in better shape to fight side effects as well as disease, the whole field listened.

Two advances primed the field for this arrival. The first, an advanced immunosuppressant that doubles as an anti-leukemia drug, fludarabine, was brought to market in 1991. Bone marrow and stem cells transplants are like any other transplant: If the recipient’s immune system is fully functional, it will simply reject the new tissue, rendering the entire procedure moot. By whacking the recipient’s immune T cells, fludarabine gives the donor’s cells a fighting chance to engraft. Unlike high doses of total body irradiation—the conventional method for beating back the immune system—fludarabine does not cause hair loss, sterility, or other serious side effects.