Bone marrow may improve odds for heart recipients
Bone marrow may improve odds for heart recipients
Same-donor infusions looks promising
Research teams at the University of Miami School of Medicine and Temple University in Philadelphia are in the midst of randomized prospective trials to see if outcomes might be improved if heart transplant patients receive a simultaneous infusion of bone marrow donated from the same person. Camillo Ricordi, MD, a professor of surgery at Miami, is a member of the team that is collaborating with investigators from Temple. The teams, sponsored by the National Institutes of Health, set out to determine whether a same-donor bone marrow infusion promotes the survival of heart transplant patients and prevents chronic rejection. "We are interested to see whether it has an effect on immediate immunosuppression and future immunosuppression," Ricordi says.
At a meeting of the International Society for Heart and Lung Transplantation in San Francisco this past spring, another group of researchers reported preliminary results that among 31 heart transplant patients given bone marrow injections, only 38% experienced episodes of acute cellular rejection, compared to 82% of the 24 patients who received heart transplant without the marrow infusion. The patients have not been followed long enough to assess chronic rejection.
Ricordi’s trials are performed in a blinded fashion so the heart transplant surgeon does not know if his patient is receiving cryopreserved bone marrow from the donor or a sample of blood from the recipient, the control group. "Other similar trails were criticized," he says, "because they were not randomized prospective, and there were problems of credibility."
He says he and his colleagues don’t know at this point whether their findings on same-donor bone marrow infusion is an important finding from a clinical standpoint. "There are indications of encouragement: From nonrandomized trials we have evidence that bone marrow infusion decreases the incidence of chronic rejection. That has also been observed in kidney transplant patients. I believe we have some evidence that this trial will extend that knowledge to heart transplants."
Chimerism seems to be key to donor-recipient coexistence. The marrow transplant produces white blood cells that recognize the donor organ and help ward off attacks by the recipient’s immune cells. The donor’s and recipient’s white cells coexist in long-term survivors, a state called chimerism. (See box, below.)
Clyde W. Yancy, MD, cardiac transplant medical director at St. Paul Cardiovascular Institute in Dallas, says he has had no personal experience with infusion of bone marrow during heart transplant, but that theoretically it’s an important step. "In essence," he says, "the Holy Grail in this business is tolerance. If we can find a way to promote organ tolerance, we can minimize rejection and the kind of toxicities and harmful side effects that are associated with the drugs that we use to suppress the immune system."
He says there’s every rationale to want to find a way to generate tolerance where the host, the heart recipient, finds a way to coexist with the donor. "One approach is to see if you can end up with two coexistent populations of white blood cells that the bone marrow recognizes. If one of them happens to be the donor organ and the other is the recipient’s own native cells, that would retard rejection."
Yancy points out that some people in the study still had problems with rejection. "The technique is clearly not absolute, but it’s a step in the right direction," he says. "As we come to understand which cells or which factors are most responsible for the rejection process and find a way to interfere with those cells, either by generating tolerance by developing a chimera, as this approach would dictate, or by finding a very specific immunosuppressant drug with minimal side effects, either situation would work."
Ricordi stresses it is feasible to procure bone marrow from the cadaver that donated the heart. He explains that bone marrow harvesting is done at the end of multiorgan harvesting from cadaver donors. "After we take the heart and liver, we take a segment of the vertebral column and send it to a specialized facility in Miami where the bone marrow is extracted." The processing of cells is complex and follows Food and Drug Administration guidelines. The vertebral column is split and marrow extracted in special rooms with positive pressure and filtered air. "Those areas are actually cleaner than regular operating rooms," he says.
Similar studies are being done on transplants of other organs such as lungs, livers, and combined kidney-pancreas. After following those patients for up to six years, results from those studies were that among 268 patients given bone marrow and organ transplants, 82% have functioning grafts compared to 77% of 131 patients who were given organ transplants alone. Among all bone marrow-organ transplant patients in studies reported so far, the overall incidence of acute cellular rejection is a little more than half, while among patients with no bone marrow, the overall rejection rate is 67%. When the trials began, researchers in Miami gave a single injection of donor bone marrow within 24 hours of the heart transplant operation. Now, they give cells over a three-day period because it seems to induce chimerism more effectively than when only a single injection is administered. The bone marrow procedure costs between $7,000 and $8,000.
Ricordi says the ultimate goal of this research is to see if bone marrow transplants can help wean patients off immune-suppressing drugs. The bone marrow treatment seems to be safe because patients are not treated with radiation to kill their own white cells before the procedures; the donor immune cells cannot overpower the recipient’s immune system and attack otherwise healthy organs.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.