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Researchers Looking for Patients to Participate in ‘Mini-Transplant’ Therapy

Researchers Looking for Patients to Participate in ‘Mini-Transplant’ Therapy

Researchers at the University of Nebraska Medical Center/Nebraska Health System (UNMC/NHS) are investigating one of the newest approaches to bone marrow transplantation with the hope that they will revolutionize certain cancer transplants. They are evaluating the safety and effectiveness of the so-called "mini-transplant" in adults with leukemia or lymphoma. The mini-transplant, which is rapidly being accepted and studied at transplant centers around the country, is performed on an outpatient basis with significantly less toxicity than is associated with a traditional allogeneic bone marrow transplant.

UNMC’s approach to the mini-transplant will involve using a familiar cancer drug—pentostatin (Nipent)—with a new twist, said Steven Pavletic, MD, a UNMC oncologist and associate professor of internal medicine. Dr. Pavletic and Greg Bociek, MD, UNMC oncologist and assistant professor of internal medicine, are principal investigators of the study.

Nonagressive Protocol

Pentostatin will be used in combination with doses of radiation that are six times smaller than those used in a traditional transplant, as well as a very gentle form of chemotherapy, Dr. Pavletic said. Because of their mildness, mini-transplants are expected to reduce the risk and side effects of graft-vs-host disease. "Our protocol is designed to be very nonaggressive," said Dr. Pavletic.

UNMC researchers aim to enroll 40 patients in the study. Half of the patients will receive allogeneic bone marrow transplant therapy from related donors, and the other half will receive bone marrow from unrelated donors through the National Bone Marrow Registry.

Those eligible for the study include patients who are responding to standard therapy, but whose disease is at a high risk of recurring, patients older than age 60, those who cannot tolerate high doses of radiation and chemotherapy, and those whose cancer recurrred after an autologous stem cell transplant.

"We use this therapy with patients who otherwise have very little hope. Instead of no chance for survival, we hope we can achieve a 30% to 50% cure rate. We want to find something for these patients," said Dr. Pavletic.

Underlying Mechanism

The premise behind traditional allogeneic bone marrow transplantation is to give patients high doses of radiation and chemotherapy, wipe out the bone marrow, wipe out the disease in the bone marrow, and wipe out the immune system to "create space" to infuse the donor’s bone marrow cells into the patient, said Dr. Pavletic.

"The theory then is that the donor’s bone marrow will engraft or become part of the patient," he added. "Then you have no leukemia and you are cured. With time, what we learned is that it’s not as simple as this."

Researchers think the success of the mini-transplant lies in what is called the "graft-vs-leukemia effect." Dr. Pavletic said he and his colleagues have learned that donor cells are probably the most critical part of therapy.

Future of Transplants

The UNMC/NHS transplant program was started by James Armitage, md, and the UNMC Lymphoma Study Group in 1982.

"I think this is where transplants are going,"said Dr. Armitage. "There is a lot to be learned but the initial promise is so clear. I think the approach of doing high-dose radiation and chemotherapy is going to be eliminated with time—probably 3 to 5 years from now. We want all this horrible toxicity associated with allogeneic transplantation eliminated.

"The mini-transplant is rapidly being accepted by transplant physicians," he added. "I truly think it’s going to revolutionize the allogeneic transplantation field. Our expectations are high, and I think the patients’ expectations should be high too."

For more information about the study, call Karen Taylor at (402) 559-6729.

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