It's called a "mini-transplant" but there's nothing diminutive about this innovative and lifesaving therapy. First developed at Fred Hutchinson Cancer Research Center in 1997, the mini-transplant is offering new hope for older patients with leukemia, lymphoma and other serious blood diseases — a population that is often medically unfit to withstand the rigors of a conventional blood (hematopoietic) stem-cell transplant. And, the therapy shows promise for treating some solid tumor cancers.
Traditional bone-marrow or peripheral-blood stem-cell transplant regimens include high doses of radiation and/or chemotherapy to destroy a patient's diseased bone marrow, followed by transfusion of donor cells to reconstitute a healthy blood and immune system. Although it cures many patients with life-threatening diseases, the process requires weeks of hospitalization and is poorly tolerated by patients older than 50 and younger patients with additional medical complications.
In contrast, the mini-transplant, developed at the Hutchinson Center by Dr. Rainer Storb and colleagues, uses a minimal dose of radiation, such that the patient's own immune system is not destroyed. Patients then receive a transfusion of donor cells and drugs to suppress the patient's own immune system to prevent graft rejection and a complication called graft-vs.-host disease. Mini-transplant recipients often require no hospitalization — and don't even lose their hair.
The key to a mini-transplant's curative powers are donor immune cells, known as T lymphocytes or T cells, which recognize the patient's cancer cells as foreign and target them for destruction — a property known as the graft-vs.-tumor effect.
The mini-transplant is not without some risks. Some cells in the mixture given to patients also recognize healthy cells, thus triggering an undesired immune response called graft-vs.-host disease, in which donor cells recognize the patient's healthy cells as foreign, sometimes resulting in destruction of healthy tissue. This can occur in transplants involving non-twin siblings or unrelated individuals.
Survival rates among patients who receive a mini-transplant range from 30 percent to 70 percent, depending on the underlying disease, disease stage and whether the patient has other illnesses at the time of treatment, according to Storb.
Hundreds of mini-transplants have been done at the Hutchinson Center and at more than a dozen other centers around the country that are collaborating with Hutchinson Center researchers to further refine the procedure. For example, the first mini-transplants were done only with donor cells from a patient's sibling; now unrelated donor cells are being transplanted as researchers find better ways to minimize graft-vs.-host disease.
Hutchinson Center researchers are now trying to improve the cancer-fighting immune response while minimizing side effects. Storb explained some of the new research:
"The initial regimen has been slightly modified by adding a drug and we are focusing right now on graft-vs.-host-disease prevention," he said. "For example, we have a randomized, phase II study going on in 2005 in which we are testing three preventive regimens in order to decrease the mortality associated with this complication. We've also recognized that in some patients with certain diseases, we want to add a little bit of anti-tumor therapy. Drs. John Pagel and Ajay Gopal have designed regimens where patients, in addition to the mini-transplant protocol, get treated with an antibody. In Dr. Pagel's research it is an antibody against a protein called CD45, which is expressed in all hematopoietic cells, and in the case of Dr. Gopal, it is CD20, which is expressed on lymphoma cells. And they've linked a short-lived radioactive isotope to these antibodies with the hope of targeting the therapy to the tumors — and thereby decrease the tumor burden."
Storb said the research team is also working in the laboratory to identify the actual target determinants that cause graft-vs.-tumor effect with the hope of eventually developing vaccines to increase the anti-tumor efficacy of these transplants.
In order to use the mini-transplant to treat more cancers, Storb and colleagues are developing a protocol for patients with acute myeloblastic leukemias and advanced myelodysplasias with a focus on patients younger than 65.
Continuing research into the uses of mini-transplants has found that the therapy may be effective for some solid-tumor cancers. In a recent study, Hutchinson Center researchers, as well as researchers at the National Institutes of Health, found that mini-transplants show initial promise as a therapy for an aggressive form of kidney cancer. The transplant eliminated or prevented worsening of metastatic renal-cell carcinoma in approximately one-third of terminally ill patients enrolled in the study. Researchers are optimistic that with further refinement, the procedure could offer new hope for patients with the disease, for which no effective chemotherapy exists.