Stem cell transplants: More patients, more cells, more cures
Karl Stasko of the Cell Manipulation Core Facility helps ready stem cells for a transplant patient.
The concept of knocking out a patient's cancerous blood cells and replacing them with healthy, disease-fighting ones may have sparkled in some scientific eyes 60 years ago, but it was not until the 1970s and early '80s that Dana-Farber and its partners in care began successfully offering adult and pediatric bone marrow and stem cell transplants.
Since then, the transplantation field has improved steadily, thanks to advances in drugs and technology that have boosted the availability of blood-making stem cells, as well as the ability of these cells to "take hold."
"One critical benefit of [allogeneic] transplants is that the donor's immune system provides an anticancer effect that lasts for months or years beyond the patient's completion of chemotherapy or radiation," says Joseph Antin, MD, chief of the Stem Cell Transplant Program of Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC). "Our goal is to harness this immunological benefit to make it more effective and reliable."
Here are some highlights of changes in adult transplants over the past few decades, as related by Antin and colleagues Robert Soiffer, MD, and Jerome Ritz, MD.
• Transplants, once considered highly experimental, "last resort" procedures, are now used more often in earlier phases of disease. They are effective with blood cancers such as leukemias, lymphomas, and myeloma, and some noncancerous blood conditions such as aplastic anemia, sickle cell anemia, and thalassemia.
• Previously limited to young patients, transplants are now an option for people into their 70s. The DF/BWCC performed nearly 370 adult transplants last year, with Dana-Farber and Children's Hospital Boston performing 70 transplants for pediatric patients.
• Stem cells now can be harvested from more sources, including the patient him/herself, relatives (sibling or parent), unrelated volunteer donors, and discarded umbilical cord blood from newborns. The chance of locating compatible stem cells for transplantation has grown to 80-90 percent.
• Finding a donor is a more rapid, refined, and accurate process, thanks to the development of molecular methods for typing tissue antigens – a critical step in determining whether donor and recipient tissue will "get along." Several million potential stem cell donors are now available through computerized registries.
• Using drugs to mobilize stem cells into the blood stream, it is now possible to collect more of these cells from patients or donors without bone marrow harvest operations. Serious infections are rarer, and patients spend less time in the hospital.
• Drugs to combat nausea, infection, cell rejection, and other potential complications have improved, as has the ability to predict which patients may develop problems.
• Reduced-intensity transplant regimens, which do not involve high-dose chemotherapy or radiation therapy, have been developed for patients not eligible for fullintensity procedures.
• Researchers are studying new agents to improve the transplant process, including growth factors, monoclonal antibodies, cytokines, chemokines, and vaccines.
"Patients go through this because transplantation offers the possibility of a long-term cure without continuing chemotherapy," says Ritz, who also heads the Connell and O'Reilly Families Cell Manipulation Core Facility at Dana-Farber, which processes stem cells. "Much progress has been made: More patients can receive this treatment, results have improved, and we understand better what happens with patients before and after transplantation. There is still room for improvement, and I'm optimistic about further progress."
