"Tricking" The Immune System By Giving Bone Marrow To Heart Transplant Patients
PHILADELPHIA -- Once a compatible organ is found and after it is successfully sewn into place and is beating rhythmically, a heart transplant patient still faces one big worry: rejection.
To ward off the acute form of rejection, which appears quickly and can be treated with immunosuppressive drugs, a patient must swallow up to 30 pills a day for the rest of his or her life.
Arteriopathy, or chronic rejection, is more insidious. It is a gradual thickening of the walls of vessels surrounding the transplanted heart, arising from the patient's own immune system reaction to the foreign organ.
Temple University School of Medicine is now in the second year of a four-year, $3 million study to investigate chronic rejection and to determine whether donor bone marrow can coax recipients' immune systems to coexist without rejection of the transplanted hearts. Funding for the study is provided by the National Institute of Allergy and Infectious Disease of the National Institutes of Health (NIH).
The trial will determine whether arteriopathy can be prevented by infusing donor bone marrow shortly after transplantation. Through a process known as microchimerism, white cells from the two immune systems blend in the recipient, inducing tolerance that protects the new organ from attack by the recipient's white blood cells.
Sooner or later, graft arteriopathy becomes a problem for every patient who receives a solid organ transplant. It affects approximately 40 percent of patients by the third year after transplantation and is the major cause of death after the first year.
"It gets everyone eventually," says Dr. Chris D. Platsoucas, chairman of Temple's Department of Microbiology and Immunology and principal investigator of the program project grant from the NIH.
Though studies have been done elsewhere on the effects of donor bone marrow in liver and kidney transplantation, Temple's study is significant because it is the first double-blind, randomized trial of bone marrow infusion in solid organ transplantation.
Any patient who meets the general criteria -- that this is their first heart transplant and they do not require any other organs -- is accepted. Neither the patients nor almost all of the Temple personnel involved in the study know who does or does not receive bone marrow with their hearts.
When the donor heart is harvested, six or seven pieces of the vertebral bone are removed as well. Within four to seven days after surgery, patients receive an intravenous solution of donor bone marrow or placebo; a second infusion is administered six days after the first.
If the Bone Marrow Infusion Trial proves that the failure of transplanted hearts can be prevented, "it will have an absolutely revolutionary effect," says Dr. Howard Eisen, medical director of Temple's Heart Transplantation Program and co-principal investigator of the study.
"If this works, it will become standard therapy for all solid organ transplants. It has a low risk and is easy to do. If we can prevent or reduce transplant arteriopathy it will mean longer survival, and much less immunosuppressive therapy."
It will also mean fewer re-transplantations. About five percent of the heart transplants performed at Temple each year are re-transplantations made necessary by arteriopathy. If those can be avoided, it will be "one of the most significant advances ever in heart transplantation," says Dr. Valluvan Jeevanandam, surgical director of Temple's Heart Transplantation Program and co-principal investigator of the study.
Temple University Health System
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