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

August 1, 2001

Researchers at the University of Nebraska Medical Center/Nebraska Health System (UNMC/NHS) are investigating one of

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

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

Nonagressive Protocol

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

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

Those eligible for the study include patients who are respondingto standard therapy, but whose disease is at a high risk of recurring, patientsolder than age 60, those who cannot tolerate high doses of radiation andchemotherapy, and those whose cancer recurrred after an autologous stem celltransplant.

"We use this therapy with patients who otherwise have verylittle hope. Instead of no chance for survival, we hope we can achieve a 30% to50% cure rate. We want to find something for these patients," said Dr.Pavletic.

Underlying Mechanism

The premise behind traditional allogeneic bone marrowtransplantation 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 outthe immune system to "create space" to infuse the donor’s bonemarrow cells into the patient, said Dr. Pavletic.

"The theory then is that the donor’s bone marrow willengraft or become part of the patient," he added. "Then you have noleukemia and you are cured. With time, what we learned is that it’s not assimple as this."

Researchers think the success of the mini-transplant lies inwhat is called the "graft-vs-leukemia effect." Dr. Pavletic said heand his colleagues have learned that donor cells are probably the most criticalpart 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 soclear. I think the approach of doing high-dose radiation and chemotherapy isgoing to be eliminated with time—probably 3 to 5 years from now. We want allthis horrible toxicity associated with allogeneic transplantation eliminated.

"The mini-transplant is rapidly being accepted bytransplant physicians," he added. "I truly think it’s going torevolutionize 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.