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| More current articles here | Updated April 2, 2005 |
April 21, 1999 - People receiving organ transplants are much less likely to reject them if they also receive some bone marrow from the organ donor. The presence of immune system cells from the donor help convince the recipient's system not to attack the new organ, Dr. Abdul Rao reports.
In lung transplants, where long-term chronic rejection is a problem, Rao said only 5% of patients who also got bone marrow showed signs of rejection, compared to 31% of those nor receiving marrow. Acute rejection of new hearts occurred in 38% of cases when marrow was also transplanted, compared to 82% of patients not getting marrow.
Rejection episodes damage the "new" organ and require strong doses of drugs to suppress the immune system. The drugs leave the patient vulnerable to infections.
Rao studied 269 patients who received bone marrow with transplants of various organs, including livers, pancreases, kidneys, intestines, hearts, and lungs. The results were compared to 131 patients who received transplants without bone marrow.
People who had long-term success with liver transplants tend to have at least some donor immune cells in their bodies that came with the liver even years after the transplant surgery. The co-existence of donor and recipient immune cells, called chimerism, is thought to be essential to long-term transplant success.
By reducing the body's tendency to reject a new organ, these cells allow lower doses of immune-suppressing drugs to be used; that reduces the chance of the patient getting an infection his immune system can't fight off. None of the patients in the study have been taken completely off anti-rejection drugs.
How does the bone marrow work? During fetal development the body's thymus gland, which controls the immune system, desensitizes systems to its own cells so the human immune system doesn't attack itself. When donor marrow cells are introduced, they seem to find their way to the thymus and deactivate systems that would attack them and their related organs.
Source: Reuters Health
November 27, 2000 - Cholesterol lowering drugs called statins may help reduce rejection after heart transplant. A 1995 study showed that patients taking statins for high cholesterol had better survival after heart transplant than patients taking placebo.
Senior investigator Dr. Francois Mach studied the effect of statins on human endothelial cells and macrophages. In both cell types the drugs reduced the effect of genes that stimulate the immune system.
In a commentary, Dr. Wulf Palinski said that before statins can be routinely given to transplant patients, more study is needed. He expressed concern that there may be currently unknown side effects to using these drugs in transplant patients. "Adverse effects on one's ability to fight infection cannot be ruled out," he said.
Source: Nat Med 2000;6:1311-1312,1399-1402
October 27, 2000 - A new method for spotting HLA-specific antibodies can identify transplant recipients at risk for rejection. Dr. Howard Gebel's team explains that a new procedure called FlowPRA is "significantly more sensitive" than standard "panel reactive" tests for spotting HLA antibodies, a sign of rejection.
Researchers did both tests on blood from 219 patients before heart transplant. Twelve patients were positive on panel reactive testing. Of the 207 with negative results on the traditional test, "72 had anti-HLA antibodies seen with FlowPRA," according to the study.
They also report, "Pre-transplant HLA levels spotted with FlowPRA were linked to actual rejection episodes that happened during the first year after transplant."
The authors also used the new method to study samples taken 3 to 6 months after transplant from 91 patients. "A positive donor cross-match was definitely associated with rejection," the researchers said.
Source: Transplantation 2000;70:1055-1059
August, 1999 - Vasculopathy is the coronary artery blockages that affect all heart recipients. It is the number one cause of heart recipient death. Heart transplant vasculopathy visible by cath at 5 years after transplant is 40 to 60%.
We investigated dobutamine stress echo as a less invasive way to check for vasculopathy. In 109 heart transplant recipients, 333 dobutamine stress echocardiograms were compared with 285 heart caths and 199 intravascular ultrasounds up to 5 years after transplant. Studies were repeated after 1, 2, 3, 4 and 5 years in 88, 74, 37, 18, and 7 patients, respectively.
The sensitivity of echo to detect vasculopathy is 57% and by cath 88%. Dobutamine stress echo increased echo's sensitivity from 57% to 72%. Worsening of dopamine stress echo results over time (a trend) indicated an increased risk of events. A normal dopamine stress echo justifies postponement of invasive studies like cath.
Based on these results, the authors started using dopamine stress echo for routine monitoring of their own heart transplant patients for vasculopathy. Once a patient has had a new heart for one year, cath is postponed if a dopamine stress echo is normal.
Title: Diagnostic and Prognostic Value of Serial Dobutamine Stress Echocardiography for Noninvasive Assessment of Cardiac Allograft Vasculopathy: A Comparison With Coronary Angiography and
Intravascular Ultrasound
Authors: Spes CH, Klauss V, Mudra H, et al
Source: Circulation. 1999;100:509-515
December, 1998 - We studied the effects of HLA mismatching and anti-rejection drug choice on early rejection in pediatric heart transplant recipients.
Between 1992 and 1997, 38 patients from age 10 days to 18 years, had 40 heart transplants. All were tissue-typed for HLA-A and HLA-B antigens, and also for HLA-DR antigens. All heart recipients were started on prednisone, and 38 got OKT3. The first 25 heart recipients received cyclosporine and azathioprine, and the last 15 were given tacrolimus.
There were 5 deaths in the cyclosporine group and none in the tacrolimus group during the study. HLA mismatching was similar between groups, with 94% of patients having 1 or 2 HLA-A mismatches and 96% having 1 or 2 HLA-B and -DR mismatches. Grades 2 to 4 rejections were greater in cyclosporine patients. Cyclosporine patients with 2 DR mismatches had worse rejection than those with one mismatch. In tacrolimus patients, there was no increase in rejection even with 2 mismatches instead of just one.
Patients treated with tacrolimus who had 2 DR mismatches had fewer serious rejection episodes than patients treated with cyclosporine who had only one DR mismatch. Grade 3 or 4 rejection episodes were not affected by HLA-A or B mismatching.
Two HLA-DR mismatches increased risk of high-grade rejection in pediatric heart transplant recipients treated with cyclosporine. The potent effects of tacrolimus lessened the impact of HLA-DR mismatching, because patients treated with tacrolimus who had 2 DR mismatches had less rejection than patients treated with cyclosporine who had one DR mismatch.
Title: The effects of HLA mismatching and immunosuppressive therapy on early rejection outcome in pediatric heart transplant recipients
Authors: Herzberg GZ, Rossi AF, Courtney M, Gelb BD
Source: J Heart Lung Transplant 1998 Dec;17(12):1195-200
PMID: 9883760, UI: 99098229
April 17, 1998 - A non-invasive test may identify heart transplant patients at high risk for rejection. Study results of 30 heart recipients followed for at least 3 months were reported by Dr. Howard Eisen.
Heart recipients who experience acute rejection within 3 months of a transplant were identified more often when using a pacemaker technique. A single diagnosis using an implanted pacemaker would eliminate the need for heart biopsy in up to 71% of routine follow-up exams. A clinical trial is in the works.
On average, patients face two episodes of rejection during the first year, with the first 3 months being the most critical. Heart biopsy is the gold standard for detecting organ rejection. Dr. Eisen says, "There is clearly a need for a less invasive and less expensive way to detect early signs of heart transplant rejection."
Contact: Joseph J. DiBartolomeo, Ph.D. DiBartoJ@mail.Temple.edu
March 30, 1998 - Local communities across the nation reacted strongly against HHS' proposed regulations to change the current organ transplant system. Under the new regulations, many regional transplant centers expect to see fewer organ donations. "It wastes more organs," said Dr. James Perkins, chief of transplant medicine at the University of Washington Medical Center. Patients awaiting transplants at the UW and similar-sized hospitals may wait 50% longer, according to UW Medical Center officials.
"Clinical outcome may be worse and the process of organ transplant may suffer if organs are prioritized for the sickest person, regardless of location," said Dr. Clifford Van Meter Jr., of Louisiana's Ochsner Clinic. "Organ donation occurs locally and is the result of concentrated local efforts," said David Lewis, executive director of Ohio Valley Life Center in Cincinnati. In addition, by removing the current regional system, costs for charter jets and patient airfare will dramatically increase the price of an already costly operation.
Watson Bell, husband of a liver transplant recipient, and former chair of the UNOS Patient Affairs Committee, said, "I am saddened that the U.S. government believes it is better able to make decisions over who lives and who dies than transplant officials. The rich patients who can afford to travel will continue to get transplants while the poor in rural areas will die."
Source: Reuters Health
September 20, 1998 - Louisiana has gone to court to keep the federal government from forcing it to participate in a national organ transplant program. A new rule by the HHS requires states to join a pool under which organs would be donated to whomever is first on the list, regardless of where they live.
The Louisiana legislature passed a law that said if an organ is donated in Louisiana, state residents get first right of refusal. Doctors here say the federal rule would allow organs donated in Louisiana to be transferred anywhere in the country. "We believe this federal rule will cause most Louisiana patients to wait much longer before receiving an organ transplant," Attorney General Richard Ieyoub said.
In a federal lawsuit, Ieyoub argues that a federal rule cannot preempt a state law. While federal laws routinely supersede state laws, there is no similar authority granted to rules, the attorney general said. The lawsuit seeks to permanently block the rule.
Source: The Associated Press
September 30, 1998 - The FDA has approved 2 portable LVADs. The devices will support transplant patients outside the hospital while they await a donor organ. Patients must be on a transplant waiting list to be eligible for the devices.
"Until now, patients on a heart-assist device had to stay in the hospital connected to a console which powered the pump," acting FDA commissioner Michael Friedman said. "These new devices allow patients far more freedom outside the hospital and may improve the quality of their lives," he said.
The devices are the HeartMate Vented Electric Left Ventricular Assist System made by Thermo Cardiosystems; and the Novacor LVAS made by Baxter Healthcare Corporation. Both units, which need to have the pump implanted surgically, can be powered by either battery packs or electricity. If patients are discharged, they must live near a hospital or transplant facility that knows how to manage the device.
Source: Reuters Health
July 1, 1999 - Cancer patients may be able to receive bone marrow transplants from donors who would otherwise be bad matches, thanks to a new immune-suppressing drug. The drug - CTLA4-Ig - suppresses only those white blood cells that cause a dangerous complication called GVH or graft versus host disease.
Other immune-suppressing drugs bring down all the body's defenses, leaving patients open to infections and other health problems. In a study published in the New England Journal of Medicine, researchers used the new drug to give marrow transplants to 12 young patients with advanced leukemia. All the patients would have died without a bone marrow transplant but the only marrow available were poor matches. After receiving bone marrow treated with CTLA4-Ig, the patients experienced no severe graft versus host disease.
The researchers said the drug, being developed by Repligen Corporation, could also make heart transplants safer.
June 1, 1999 - Drugs that teach the body to accept transplanted organs have remained effective for up to a year in monkeys who got kidney transplants. Researchers are planning human trials, said Dr. Allan Kirk of the Naval Medical Research Center in Bethesda, Maryland. He described the monkey study in the June issue of the journal Nature Medicine.
Two years ago, Kirk reported on a similar treatment that prevented rejection for 9 months in monkeys. The new treatment includes only one of the 2 substances used in the first trial.
The goal is to teach the immune system to accept transplanted organs rather than attack them. To do that, researchers injected the monkeys with a protein to prevent certain blood cells from delivering a "danger" signal to other cells - a danger signal that triggers the body's rejection process. The protein is called hu5C8.
The researchers gave it to 9 monkeys just after kidney transplant surgery. The monkeys then received it once a week for 4 weeks after that, and finally once a month for 5 months. Eight of the 9 treated monkeys remain alive with no organ rejection. Two have lived about a year so far since the end of treatment, and another for more than 6 months.
Source: Nature
October 15, 1999 - Proposed regulations from HHS to change distribution of organs for transplant would be permanently blocked under legislation approved by the House Commerce Committee Wednesday. The bill, which would reauthorize programs under the National Organ Transplant Act of 1984, would also strip HHS of much of its authority to oversee UNOS - the contractor that runs the organ transplant network. "Responsibility for organ transplant standards belongs in the private sector," the bill says.
"This bill would strengthen the independence of the organ transplant network," said the Commerce Committee Chairman. The bill's sponsor, Michael Bilirakis, says, "This recognizes that decisions about organ transplants and allocation are best left to the medical community, as Congress intended." President Clinton claims the legislation is nothing but a power grab by UNOS. He says UNOS wants to stop efforts to make the process more fair in order to protect the economic interests of transplant centers that could lose patients if the new rules pass. The Clinton administration vows the President will veto the bill.
Source: The Associated Press
November 18, 1999 - New transplant rules were in serious jeopardy today. In a late-night move, Senate Majority Leader Trent Lott slipped language into a bill that puts the rules on hold for 4 months.
The move came despite a deal negotiated between Congress and the White House last week. The new language would require a 90 day delay, then HHS would have to issue the rules again, causing another 30 day delay for public comments. HHS would then have to consider those comments. A delay of several months would give Congress time to return next year and pass pending legislation that would strip HHS of its power to arbitrarily set such rules in the first place.
The rules have been on Congressional hold since February of 1998. Under the current system, organs are distributed within local areas and then within regions. Supporters of the current system argue that local distribution encourages people to donate organs, knowing they will stay in the area.
As debate heated up in Washington, UNOS - which runs the transplant system - was in Baltimore for its semiannual board meeting. The network has fiercely opposed the regulations, but officials were prepared to begin writing a new policy. Under the rule, the network would have just 3 months to come up with a new way to distribute more livers, regardless of location. Both the spending bill with its 42 day delay, and the tax bill with the longer delay, must be signed before the year is out.
February 29, 2000 - The FDA has approved 2 test kits (assays) by Bio-Rad Laboratories for testing organ donor (corpse) blood samples for HIV and hepatitis B virus. The assays will mainly be used by tissue donation centers to check the safety of organs for transplant. The HIV assay tests for both HIV-1 and HIV-2. They will be marketed by Genetic Systems Corporation in Redmond, Washington.
"Bio-Rad is currently the only company to have FDA approval for testing cadaver samples," company officials said. "These enzyme immunoassay tests are sold as complete kits."
Source: Reuters Health
May 17, 2000 - Analyzing a registry of 5,000 heart transplant patients showed that survival was greater in the MMF (mycophenolate mofetil or CellCept) group compared to the azathioprine group. At one year, survival was 96% versus 93% and at 3 years, survival was 91% versus 86%.
A total of 5,599 patients were analyzed (4,942 patients got cyclosporine and azathioprine, while 657 took cyclosporine and MMF). Outcomes investigated at one year included rehospitalization, ejection fraction and survival. There were no differences in rehospitalization rates between the 2 groups. Ejection fraction at one year was slightly higher in the MMF group (59.4%) compared to the azathioprine group (57.6%).
The analysis included only patients who were on cyclosporine-based therapy, had survived long enough to be discharged from the transplant hospitalization, and were transplanted in the USA.
Source: Medscapewire
From: The 20th Annual Scientific Sessions of the International Society of Heart and Lung Transplantation
January, 1998 - Dr. Abraham Shaked and his team knew that 2 molecular signals trigger rejection. The signals start in a molecule known as MHC (Major Histocompatibility Complex). Responding to a perceived threat, MHC sends out 2 separate signals aimed at telling the immune system's T-cells to attack.
The Pennsylvania team engineered virus cells to carry genes that stimulate production of a protein called CTLA41g. This protein can block the second signal that switches on a T-cell attack. This engineered virus was mixed into the solution used to preserve donor livers before transplant. Surrounded by the solution, the liver "soaked up" the virus and along with it, the CTLA41g-manufacturing gene.
As a result, the livers were primed to prevent rejection before being transplanted. "We delivered the gene for a protein that stops the immune system from attacking the organ," Shaked explained, "and we were able to do so with a single treatment that removed the need for follow-up drug therapy. Although not now available, there is clear potential for future use. Future studies are needed."
Title: Gene Therapy Aids Organ Transplant
Source: Nature Medicine (1998;4:194-200)
November 5, 1998 - Taking a tip from tiny animals that can live for more than a century, Japanese researchers have invented a new way to store organs for transplant. If organ banks similar to blood banks could result, the frantic rush to bring organs straight from donors to the operating table could be avoided - hearts only last outside the body roughly 4 hours. This would allow more exact tissue matches, lessening rejection, and drug use and side effects. The main problem with keeping organs in storage is that water damages cell membranes at low temperatures. Removing water from tissues usually causes equal damage = Catch 22.
Kunihiro Seki knew that animals called tardigrades can stand extreme conditions by losing most of the water in their bodies (In Brief, 31 October, page 26). They can survive in this state for a century or more. When water was added to a dried-out moss kept in a museum for 120 years, tardigrades were soon found crawling all over it. To achieve this, tardigrades use a sugar called trehalose to stabilise the structure of their cell membranes. "This suggested that the same mechanism could apply to preserving mammal organs," says Seki.
To test this, the team flushed rat hearts with trehalose solution before packing them in silica gel to remove the water from their cells. The hearts were then immersed in perfluorocarbon, an inert compound, and stored at 4°C in airtight jars. Ten days later, the team took the hearts out of the jars and resuscitated them. Within half an hour, they were beating again. Measurements of their electrical activity suggested that the heart cells survived intact.
Seki believes the trehalose and perfluorocarbon replace the water inside the cells, preventing tissue damage. The researchers plan to prolong the storage for up to a year. Perhaps within a few years, the technique could be used to preserve human organs.
Source: The New Scientist
January 12, 2000 - The antirejection drug FK 506 reduces blood clot formation compared to cyclosporine in heart recipients. The drug may also help prevent heart transplant vasculopathy (CAD), researchers report in the December issue of The Journal of Heart and Lung Transplantation.
Dr. Ronald Freudenberger studied blood's tendency to clot. Blood from 17 patients who had a heart transplant was constantly circulated through a perfusion machine. Seven of the patients had been treated with tacrolimus for at least 2 weeks, and 10 had been treated with cyclosporine for at least 2 weeks. None of the patients were using blood thinners.
The researchers found significantly less clot formation in the FK 506 group compared to the cyclosporin group. The researchers say this finding "suggests that tacrolimus may help prevent heart transplant vasculopathy." They add that tacrolimus seems to work by impairing "one or more of the anticoagulant pathways."
Title: FK506 Has Better Antithrombotic Effect Than Cyclosporin After Heart Transplant
Source: J Heart Lung Transplant 1999;18:1228-1231
November 13, 2000 - OKT3 given along with other immunosuppressive drugs may successfully treat children with acute myocarditis - this may prevent need for heart transplant in such children. A UCLA team described 5 acute myocarditis patients from 15 months to 16 years of age. They were treated with a combination of OKT3, immunoglobulin, prednisone, cyclosporine and azathioprine.
In acute myocarditis, "an autoimmune function happens that can permanently damage the heart," Dr. Juan Alejos said. Using OKT3, they were able to reverse damage to the heart's ventricle. "It is an aggressive therapy that is very effective," he added. They have successfully treated 9 patients this way so far. "If we can get patients with acute myocarditis early enough, we have a good chance of reversing damage to their heart."
Dr. Alejos added that the patients, who were treated 3 to 4 years ago, "all have normal heart function, none are listed for transplant, and none are on any heart failure meds." One patient had a brief relapse several months after therapy, but responded to steroid treatment and is now free of medication.
Source: J Heart Lung Transplant 2000;19:1118,1121
September 6, 2000 - Researchers now think that only the sickest heart failure patients with a high risk of dying on the waiting list have a sufficient survival rate after transplant. Dr. Mario Deng and colleagues reported their findings in the September 2nd issue of the British Medical Journal.
They studied all 889 adult patients listed for a first heart transplant in Germany in 1997. The patients' risk of death from heart failure was classified as low, medium, or high. Over one year, they found that the high-risk patients had
the highest overall death rate, the highest risk of dying on the waiting list, and received a transplant more often.
A heart transplant improved survival only for patients at highest risk of death. "Patients with low to medium predicted risk had no reduction in risk of death with transplant; they should be managed with other therapies," say Dr. Deng and colleagues.
In a commentary, doctors Tom Treasure and Andrew Murday write that the results are "at odds with strongly held beliefs of those involved, both doctors and patients." They suggest that a clinical trial is necessary to test whether transplant improves survival in these patient groups.
In another editorial, Dr. Sharon Hunt says the findings "will probably spur development of organ allocation plans that only give donor hearts to those most likely to get survival benefit from them, and will help define that group of patients."
Source: BMJ 2000;321:526,540-545
All information on this site is opinion only. All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor. Use the reference information at the end of each article to search MedLine for more complete and accurate information. All original copyrights apply. No information on this page should be used by any person to affect their medical, legal, educational, social, or psychological treatment in any way. I am not a doctor. This web site and all its pages, graphics, and content copyright © 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004, 2005 Jon C.