Mass. General transplant method prevents organ rejection
By Patricia Wen, Globe Staff
A Massachusetts General Hospital research team is reporting a major advance in the years-long effort to overcome the rejection of organ transplants.
Four out of five patients who underwent an experimental kidney transplant were able to stop taking powerful immunosuppressive drugs, and they have so far lived between 15 months and almost five years without experiencing rejection. At the time of their transplant, the patients received bone marrow from the same donor.
The report in tomorrow's New England Journal of Medicine is considered particularly significant because the patients received kidneys that were different from their own tissue type. Transplants of such mismatched organs are the most common, and the most likely to be rejected, even when patients take immunosuppressive drugs.
One of the five patients rejected the kidney during the experimental program, and researchers ultimately concluded that was due to an unexpected antibody reaction. The team later tweaked their protocol to include a new drug to prevent such a scenario from happening again.
Dr. David H. Sachs, a 66-year-old Harvard Medical School professor who has spent his career trying to induce tolerance for organ transplants, said he was encouraged by his team's "initial success" with the procedure.
"While we need to study this approach in a larger group of patients before it is ready for broad clinical use, this is the first time that tolerance to a series of mismatched transplants has been intentionally and successfully induced," said Sachs, who co-authored the study with two transplant surgeons, Dr. Tatsuo Kawai and Dr. Benedict Cosimi, as well as a dozen other researchers at Mass. General.
Sachs, director of Mass. General's Transplantation Biology Research Center, has long believed that a donor's bone marrow -- from which immune cells originate -- could play a pivotal role in giving transplant patients "induced tolerance" to a donated organ.
Under Sachs' approach, five days prior to transplant surgery, patients begin low-dose chemotherapy to kill off some of their own marrow cells and make room for the injection of the donor's bone marrow.
The patients also receive a drug and radiation to the thymus to eliminate a type of immune system cell, known as a T cell, that typically attacks any tissue perceived as foreign.
On the day of the procedure, surgeons attach the new kidney while injecting the donor's bone marrow into a blood vessel in the patient's arm. The donor's bone marrow mixes with the patient's, creating a temporary state called "mixed chimerism." This tricks the patient's immune system into recognizing for years -- and possibly forever -- the donated organ as part of the "self."
After the surgery, the immune system is still in a period of adjustment, and doctors give patients anti-rejection drugs that are gradually tapered off. Most patients were off the drugs by the ninth month.
Sachs first tried this approach successfully on mice, pigs, then monkeys. In 1998, he won approval to try his treatment on a select group of Mass. General patients with severe kidney failure, all of whom were offered matching kidneys from close relatives. When these six patients did well, Sachs moved on to the most ambitious test of his method, trying it out on patients with mismatched donors.
Sachs' study represents a pivotal moment in organ transplantation, organ transplant researchers say. It shows that it may be feasible to eliminate immunosuppressive drugs with their debilitating side effects, such as skin warts, cataracts and increased risks of heart disease, diabetes and serious infections. Also, patients may no longer need to live with the fear of organ rejection. Within 10 years, half of all transplanted kidneys fail because of chronic rejection, a bleak predicament in this era of organ shortages.
"This is landmark work," said Dr. Joshua Miller, an organ transplant researcher from Northwestern University's Feinberg School of Medicine in Chicago. "It gives us hope that recipients of organ transplants will be relieved of being on chronic immunosuppressive drugs for the rest of their lives."
Researchers cautioned, though, that only the healthiest patients may be able to endure the rigorous pre-transplant treatments.
Consider trying it with a pig. Transplant marrow from the patient into the pig first, this may effect it's organs in a similar way, setting up the organs as both. Then the pig marrow to the patient followed by the required organ.
wow this is promising research.
my daughter needs a kidney.
she's been waiting for about 18 mos.
Having received both a living related kidney and a cadaveric pancreas from Dr. Cosimi's team, all with great success, I have tremendous confidence that once they determine that it is truly the breakthrough apparent, it will be safe. i intend to outlive these organs and hopefully when I come back for seconds, this process will be perfected . As the immunosuppressant drugs present the only material risk post operatively, a process like this, once perfected, will result in fewer wasted organs and, in turn, a swift reduction in the ' lists '.
Congratulations doctors, if this pans out, history will look back kindly upon you.
This is remarkable great thinking. Instead of using chemotherapy and patient bone marrow, it should also be able to be done using molecular method, such as using recombinant protein and antibodies. The only concern is that the market is a little too small for industry to develop the needed materials.
I underwent a simliar trial at Beth Israel Deaconess (Dr. Anthony Monaco & Dr. Martha Pavlakis) back in '04. Instead of getting the marrow, I received an infusion of my donor's blood marrow stem cells. I was weaned off prednisone and Neoral but now take CellCept and Rapamune instead. So far, so good. Sure, I'd be happy not to take any drugs at all, but any day not hooked up to a dialysis machine is a good day!
Great job!! you are the Real Gods on earth!!!
My Uncle who is very much in need of Kidney trasplantation operation lives in India.he is waiting since 2003 and his age is 42 now.He is going for dialysis twice in a week.
Is it possible to do this operation for him????
Thanks in Advance,
Rani
Rani,
Mass. General says the next phase is not yet enrolling patients. But they are keeping a list of people who inquire.
Elizabeth Cooney
White Coat Notes
As a laboratorian involved in assessing immunosuppressant drug levels, I welcome the possible advent of reducing the need for monitoring drug levels so frequently. Think of the impact on already shrinking healthcare resources.
I hope each of the correspondents above has written in parallel to protest the attacks by PETA and others on medical researchers' use of animal models. Or actively contributed to FBR, the Foundation for Biomedical Research.
Frank
Is there a way to become part of Dr. Sachs study....I have a hereditary kidney disease and my kidneys are failing. I need a transplant and would be interested in being part of the cases that are being treated by this method.
What is the possibility of using this method for type I diabetics? If a matching donor could give islet cells and stem cells or bone marrow, would this be the answer? Or would the cure still be worse than the disease?
I am currently under the care of Doctor JH at NEMC and have polysystic kidney disease.......My kidneys are operating at 11 per cent and I will soon have to go on dialysis.....I have a friend who has agreed to donate kidney and is going through the process now...Everything looks good as of now for the transplant.....At age 30 and in good physical condition would I be a good candidate to participate in your study........Keep up the good work!!!!!!
Less than a year ago my parents went through a kidney transplant in Romania .My father was the donor because my mother had a kidney failure 5 years ago, due to an autoimmune disease(Rapidly progressive glomerulonephritis- anti GMB).
At this point the transplanted kidney is functioning perfectly, but my mother is confronting problems with the immunosuppresants drugs.
Can my mother receive the donor's (my father) bone marrow at this point?
Does this experiment include other organs as well. Only the kidney is mentioned. My daughter needs a double lung transplant and I'd be very interested in knowing if it's been tried on lung transplantation or is it a possibility in the near future???
Great job...medicine has come a long ways and gives us new hope in believing!
Your feedback would be very much appreciated!!
MY daughter (12) is receiving a kidney on 6/17/08 from her brother-in-law. I would love someday if she could be free of the required presnt meds. I thought the bonemarrow sharing donor to recipient was only trial ? Can my son in law provide marroow at a later date? My daughter is adpted from china no records
of blood relatives available to us. Does it work as well with non related donors?
ANY feedback would be greatly appreciated.ILL hope and pray this becomes
successful medical practice keep going...................
I would like to know if this system of bone marrow can be done of patients transplanted 2 years ago because i was tranplanted in Feb,2006
Nambaje Elias,
I do not know the answer to your question, but here is the person to contact at Mass. General Hospital:
Nina Tolkoff-Rubin
Director of Hemodialysis and CAPD Units
Medical Director for Renal Transplantation
Massachusetts General Hospital
Elizabeth Cooney
White Coat Notes
This blogger might want to review your comment before posting it.
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