An immune booster
A method developed at Dana-Farber over the past few years seeks to strengthen the GVL side of the equation. Technically called non-myeloablative transplants, but better known as "mini" transplants, these procedures involve giving patients relatively low doses of chemotherapy followed by an infusion of disease-fighting T cells from a compatible donor. This method, available through clinical trials, has become a promising partner to full-scale stem cell transplants.
Traditional transplants embody the principle of overwhelming force in fighting disease: using high-dose therapy to send cancer into submission, then "rescuing" patients with a transplant. Mini transplants are more subtle weapons, says Dana-Farber's Edwin Alyea, MD. Low, initial doses of chemotherapy "stun" tumor cells into not growing for a while; infusions of donated T cells then take up the main battle against the cancer.
The clinical and laboratory leaders of adult stem cell transplantation at Dana-Farber include (left to right) Jerome Ritz, MD, Robert Soiffer, MD, Joseph Antin, MD, Arnold Freedman, MD, and John Gribben, MD, DSc.
The technique essentially reverses the roles that chemotherapy and donor tissue have long played in transplants, Alyea observes. While high doses of chemotherapy and/or radiation have traditionally done the brunt of the cancer-killing work, the low doses of chemo in mini transplants serve mostly as stagesetters for the transplanted T cells. "The chemo quells the growth of the cancer cells long enough for the immune cells to engraft — take hold within the body — and multiply," Alyea remarks.
Clinical trials of non-myeloablative transplants at DFCI and BWH are open to patients at high risk for complications from a conventional transplant because they are elderly, have other medical problems, or have relapsed after a previous stem cell transplant. Physicians at the two institutions have performed more than 100 of these transplants over the past couple of years, and they have found the procedure works best for patients with chronic lymphocytic leukemia, multiple myeloma, low-grade Hodgkin's lymphoma, preleukemia, and some acute myeloid leukemias.
"We're encouraged by the results so far," Alyea says. "Patients generally tolerate the lower doses of chemotherapy well, and the donor cells often grow well after transplant." He adds, though, that the technique is still evolving and has substantial room for improvement. Researchers are now working to customize it for specific diseases.
Although mini transplants spare patients intense-dose chemotherapy, "there is nothing 'mini' about the risks they entail," stresses Alyea. Recipients face the same odds of developing GVHD that conventional transplant recipients do. "We still have much to learn about how mini transplants work on a molecular level," he says. "That will be essential to our ability to reduce complications."
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