April 14, 2003
The state of the art in stem cell transplantation
Regina Sheldon donates stem cells for her sister with help from nurse Sue Skop.
The original idea behind bone-marrow transplantation was daring but straightforward: Treat leukemia patients with high doses of chemotherapy to kill as many cancer cells as possible, then give them a transplant to replace their marrow, which had been destroyed by the chemotherapy. The fresh marrow cells would take up residence inside the bones, where they would begin producing vital components of blood and the immune system.
For all the challenge and complexity of the procedure — and the fortitude it requires of patients — transplants were conceived essentially as "supportive" therapy, a way of overcoming the damaging side effects of high-dose chemo and radiation treatments.
But bone marrow had some surprises in store for physicians and researchers.
"As we gained more experience with transplants, it became clear that much of their benefit comes from marrow itself," says Jerome Ritz, MD, of Dana-Farber's Adult Hematologic Malignancies program. "The new tissue not only takes the place of what has been lost, but immune cells within that tissue attack leftover leukemia cells — what is known as the graft-versus-leukemia (GVL) effect."
When patients receive a bone marrow transplant or its newer cousin, a peripheral blood stem cell transplant, "they're being given a new immune system," Ritz explains. "Marrow and stem cell transplants are coming to be thought of as immune-based therapies in their own right."
The discovery of the GVL effect has given fresh energy to efforts aimed at improving bone marrow transplantation — to increase its effectiveness while making it safer for patients. Dana-Farber, which operates one of the largest adult transplant services in the world with its inpatient partner, Brigham and Women's Hospital (BWH), is also a center for some of the most innovative research in the field. The same is true of pediatric transplants, conducted through a separate program at Dana-Farber and Children's Hospital Boston.
The clinical and laboratory leaders of adult stem cell transplantation at DFCI include (l. to r.) Jerome Ritz, MD, Robert Soiffer, MD, Joseph Antin, MD, Arnold Freedman, MD, and John Gribbon, MD, DSc
Institute physicians performed their first bone marrow transplant more than 30 years ago, just a short time after the procedure had proved practical. In November 2002, the Institute marked its 500th adult transplant using stem cells from an unrelated donor. The total number of adult transplants performed at DFCI and BWH is in the thousands. Today, as in the past, the focus is not solely on providing the best clinical care possible, but on finding ways to boost the procedure's chances of success and minimize risks and complications.
Adult transplant research at Dana-Farber and Brigham and Women's encompasses nearly 30 clinical trials evaluating new transplant techniques and supportive therapies in patients. It also includes a wealth of laboratory studies in which scientists seek basic molecular explanations of why transplants work and why they sometimes spawn problems of their own.
It is the collaboration between investigators in the lab and clinic, as much as the ingenuity of the researchers themselves and the courage of patients in clinical trials, that has enabled the two hospitals (allied as the Dana-Farber/Brigham and Women's Cancer Center) to offer transplant procedures that are truly state-of-the-art.
Next page: Bone marrow basics
