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Transplant Update

More articles here           Updated July 18, 2006

 Transplant Meds Benefit Better

January 1, 2002 - Section 113 of the BIPA (Benefits Improvement) Act of 2000 removes Medicare time limits for covering immunosuppressive drug costs for heart transplant recipients. If your benefits for anti-rejection drugs ran out in the past, you can now get them again. This does not apply to such drugs used for end-stage kidney disease. The drugs covered area:

Source: www.cms.hhs.gov/providerupdate/april2002/janinstruct.asp
Medicare Human Services (DHHS) Hospital Manual Centers for Medicare & Medicaid Services (CMS), Transmittal 781.

 Weight Lifting Okay For Heart Recipients

December 19, 2001 - A recent study suggests that one long set of leg presses at moderate intensity is safe in heart recipients. Dr. Neil McCartney classed 23 patients into 3 groups and studied 4 areas:

 Patient Groups   Areas Studied 
Early
3 months after transplant - 6 patients
Intermediate
1 to 3 years after transplant, 7 patients
Late
5 to 14 years after transplant, 10 patients
  • on their back at rest
  • upright at rest
  • doing leg-presses -
    28 repetitions over 2 minutes 20 seconds
    at 50% of capacity
  • recovery

Right-heart cath was used to measure right heart pressures and cardiac output. Regular blood pressure and heart rate were recorded continuously with a finger cuff.

 Group   Cardiac Ouput   Heart Rate   Peak Systolic BP 
 Early  30%   5%  179 mmHg (15% increase)
 Intermediate  40%  11%  180 mmHg (27% increase)
 Late  54%  16%  176 mmHg (28% increase)

"Average pulmonary artery pressure did not exceed 30 mmHg and average PCWP did not exceed 15 mmHg in any group during the weight lifting," the investigators say. "[to meet the] needs of heart transplant recipients, future research should focus on training programs which include weight lifting exercise," Dr. McCartney concludes.
 
Source: Int J Cardiol 2001;81:61-74 and Reuters Health

 Pumping Iron

June 18, 1996 - Robert Lewis had a heart transplant at Shands Hospital 2 1/2 years ago. He is now in a weight lifting program designed to prevent osteoporosis, which commonly occurs as a side effect of the prednisone taken to prevent organ rejection.
     Randy Braith, an exercise physiologist says, "Multiple medications are given to transplant patients to prevent rejection, such as cyclosporin, azathoprin, and prednisone. One side effect of prednisone is thinning of the bones." Almost 100% of the people who have heart transplants develop osteopenia, or weakening of the bones, and half of these people will develop osteoporosis, a serious disease that can cause spontaneous fractures. Mr. Braith continues, "We measured bone density in heart transplant patients and began a program of weight lifting after surgery to see what effect pumping iron might have on strengthening bones."
     What they discovered was that bone density in heart transplant patients after surgery showed up to 25% loss during the first 2 months alone. However, transplant patients who began weight training 2 months after transplant surgery were able to recover and maintain bone density to the same level it was before the operation
     Braith and cardiologist Roger Mills enlisted 16 transplant patients for the study. Bone density was measured at study start, at 3 months, and again at 6 months. Researchers split patients into 2 groups: a control group that did only aerobic exercises and another group that combined aerobic exercises with weight training 3 times a week.
     In the weight-training program, people used a machine that isolates the lower back, an area where bones weaken quickly and break easily. Patients also used 8 other upper and lower body exercise machines.
     "A good strength building program can balance the effects of prednisone,"Dr. Mills said. "Patients can go back to work and not fear having fractures, which can affect a person's ability to sit, stand and bend."
 
For more information contact Nancy E. Dohn or Arline Dishong at 352-392-2621

 Exercise Important After Transplant

January 28, 1999 - In the January 28th issue of The New England Journal of Medicine, Dr. Jon Kobashigawa says there has been "reluctance to prescribe exercise training after heart transplant."
     Researchers randomized 27 heart transplant patients to either standard therapy or structured rehab for 6 months. Patients in the exercise group started exercising two weeks after transplant. Compared to non-exercising patients, people in the exercise group showed "significantly greater increases" in work load capacity (59% versus 18%), and peak oxygen consumption (49% versus 18%) or Vo2max.
     "Exercise training was well tolerated," the authors add, "and training did not increase rejection." Based on their findings, they recommend that structured exercise programs "be considered standard post-operative care for heart transplant recipients."
 
Source: N Engl J Med 1999;340:272-277

 Fewer Meds, Better Results

March 1, 1997 - One of patients' biggest expenses after a heart transplant is the cost of cyclosporine. In a study in the New England Journal of Medicine, Australian doctors showed that giving patients a fungus-fighting medicine called Nizoral can reduce the need for cyclosporine by 80%. It works by slowing the body's tendency to break down cyclosporine.
     The net saving was $5,200 in the first year after transplant and $3,920 each year after that. Also, patients taking the anti-fungus medicine were less likely to reject their transplanted hearts.
     In the same issue of The Journal, Dr. Jon Kobashigawa described another approach to improving heart transplant outcomes. They found that giving patients a cholesterol-lowering drug in addition to their anti-rejection medicine protects against rejection and substantially improves survival.
     Doctors tested the cholesterol drug Pravachol on 97 patients. One year after surgery, 97% of those taking Pravachol were still alive, compared to 78% who did not take the drug. The UCLA study was financed partly by Bristol-Myers Squibb, which makes Pravachol.
 
Source: Associated Press

 Breath Test Cuts Need For Biopsies

March 19, 2002 - More than 23,000 heart recipients have heart biopsies at least once every year. It is invasive, tiring, and expensive. Is it possible to spot organ rejection just by analyzing a breath sample?
     Rejection causes oxidative stress in the heart, which releases substances called alkanes in the breath. Researchers studied measuring these substances and relating the measurements to organ rejection. They studied how alkane levels related to each grade of rejection.
     539 heart transplant recipients had 1,061 heart biopsies at 7 medical centers. Biopsies were reviewed by 2 independent pathologists. The pathologists agreed in 743 biopsies and disagreed in 318. Obviously, better methods of testing for organ rejection are needed.
     Patients had breath analysis before each biopsy. These breath samples were analyzed for alkanes and methylalkanes. The results were:

 Grade of Rejection   Percentage of Patients 
Grade 060.8% (645 biopsies)
Grade 1A18.6% (197 biopsies)
Grade 1B7.9% (84 biopsies)
Grade 28.8% (93 biopsies)
Grade 3A4.0% (42 biopsies)

The positive predictive value of the test was only 6% or 24 of 419 biopsies. However, the negative predictive value of the test was 97% or 565 of 581 biopsies. So heart recipients who are going to have a heart biopsy and who have a breath analysis that is positive should still have the biopsy - the test does not predict the presence of rejection.
     On the other hand, if the breath analysis is negative, a biopsy is not needed because the breath test very accurately predicts cases where there is not any organ rejection. Applying this test would reduce the number of needed heart biopsies by 58%. This test can be done with an easy to use breath analyzer that measures these organic compounds released by the rejection process.
 
From: ACC Meeting, 2002
Topic: The HARDBALL Study - Heart Allograft Rejection Detection with Breath Alkanes in Low Levels
Presenter: Dr. Michael Phillips of Menssana Research, Inc

 New Anti-Rejection Drug Looks Good

March 2, 2000 - A new drug reduces rejection in heart transplant patients without increasing their risk of infections and cancer. The drug is known as daclizumab (Zenapax), according to a report in the March 2nd issue of The New England Journal of Medicine.
     "Daclizumab safely reduces the frequency and severity" of heart transplant rejection, says Dr. Ainat Beniaminovitz. Organ rejection occurs when the immune system attacks the donor organ. To avoid this, patients take drugs that suppress the immune system. Those drugs leave patients open to cancer, infections, and other serious side effects.
     Daclizumab is more specific than other anti-rejection drugs. It only blocks "activated" immune system cells that would attack the heart. Other immunosuppressant drugs block the whole immune system.
     In the study, 28 heart transplant patients took daclizumab in addition to other immunosuppressive drugs. On average, these patients had fewer rejection episodes than 27 patients who did not take daclizumab. Also, it took daclizumab patients longer to experience their first rejection episode, which is important because most episodes of rejection occur in the first 3 months after surgery.
     The daclizumab patients were just as likely to have infections or cancers compared to people who did not receive the drug, according to the report. The new drug did not seem to cause any major side effects. Beniaminovitz' center now uses daclizumab routinely in heart transplant patients.
     Another benefit of the drug is that it lets doctors "use less prednisone and other immunosuppressive drugs," according to Beniaminovitz.
 
Source: The New England Journal of Medicine 2000;342:613-619

 Tacrolimus Versus Cyclosporine

April 18, 1999 - We studied tacrolimus use after heart transplant, including side effects compared to cyclosporine. Eighty-five patients having their first heart transplant were randomized to either tacrolimus (39 people) or cyclosporine (46 people). All patients received 3-drug therapy, and 15 patients (18%) took OKT3 due to pre-transplant kidney failure. Heart biopsies were done at weeks 1, 2, 3, 4, 6, 8, 10, 12, 24, and 52. The study lasted one year.
     Patients were 87% male, 90% Caucasian, and an average age of 54 years. Fifty-five percent had heart transplant due to coronary artery disease and 41% due to dilated cardiomyopathy. Patient and graft survival were the same in both groups. Risk of organ rejection was the same in both groups.
     Through one year of follow-up, blood tests were similar except that the cyclosporine group had higher LDL, HDL, and triglycerides, requiring more cholesterol-lowering drug use. There were no differences in kidney function, blood sugars, magnesium or potassium levels during the first year. More cyclosporine patients (71% versus 48%) developed high blood pressure requiring drug treatment. Risk of infection was the same for the two groups (2.6 episodes per patient per year).
     Researchers concluded that tacrolimus seems safe and effective for preventing rejection during the first year after heart transplant. It caused less high blood pressure and less high cholesterol, and has no more side effects in other areas than cyclosporine.
 
Title: A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus
Authors: Taylor DO, Barr ML, Radovancevic B, Renlund DG, Mentzer RM Jr, Smart FW, Tolman DE, Frazier OH, Young JB, VanVeldhuisen P
Source: J Heart Lung Transplant 1999 Apr;18(4):336-45
PMID: 10226898, UI: 99243485

 Everolimus Reduces CAD

August 28, 2003 - Blocked coronary arteries are the most common problem for heart recipients. Most show signs of this within 5 years after transplant. The leading causes of death in transplant patients who live at least 5 years are chronic rejection and cancer. Anti-rejection drugs worsen - and may cause - both problems.
     The blocked artery problem is called many things but the result is the same as with CAD. Other names include vasculopathy, chronic rejection, transplant disease and posttransplant lymphoproliferative disorder or PTLD.
     A new drug named everolimus (Certican) was tested against a standard anti-rejection drug called Imuran (azathioprine) for preventing transplant disease. The trial was led by Dr. Howard Eisen and was funded by Novartis, maker of the drug. Results were quite good.
     Doctors at 52 heart transplant centers studied 634 patients having their first heart transplant. One third of the patients (214 patients) took azathioprine at a dose of one to 3mg per kilogram of body weight per day. Another third (209) took 1.5mg everolimus daily. The remaining third (211) took 3mg everolimus. All patients also took steriods, cyclosporine, and statins (cholesterol-lowering drugs).
     The trial's primary end point was death, need for another heart transplant, acute rejection grade 3A or worse, or rejection that seriously reduced heart function.
     Thirty-six percent of patients taking everolimus at 1.5mg reached the primary end point; 27% of the higher dose everolimus patients did so; while 47% of azathioprine patients did. Most of that difference was from rejection serious enough to require extra treatment. The number of deaths and need for another heart were similar between all groups.
     Fewer low dose (36%) and high dose (30%) everolimus patients developed CAD than azathioprine patients (53%). Cytomegalovirus infection was less in the low dose (8%) and in the high dose (8%) everolimus group than in the azathioprine group (22%). However, everolimus patients had slightly reduced kidney function and slightly higher cholesterol levels.
 
Source: AP
Source: N Engl J Med. 2003 Aug 28;349(9):847-58
Comment in: N Engl J Med. 2003 Aug 28;349(9):829-30 and N Engl J Med. 2003 Dec 4;349(23):2271-2; author reply 2271-2.
Title: Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients.
Authors: Eisen HJ, Tuzcu EM, Dorent R, Kobashigawa J, Mancini D, Valantine-von Kaeppler HA, Starling RC, Sorensen K, Hummel M, Lind JM, Abeywickrama KH, Bernhardt P; RAD B253 Study Group.
PMID: 12944570.

 Everolimus On Track For FDA Approval

October 21, 2003 - Novartis Pharma AG announced today that it has received an "approvable" letter from the US FDA for Certican (everolimus), to be used with cyclosporine to prevent rejection after heart or kidney transplant. Final approval awaits more data from Novartis for FDA review.
     Certican received its first approval from the Swedish Medical Products Agency in July of 2003. In Canada, Certican has received a fast-track designation for use in heart transplant patients.
 
Source: Novartis.

 Protein Level Spots CAD Early

July 27, 2000 - Heart transplant recipients with chronically high levels of troponin I are at high risk of transplant CAD. Dr. Carlos Labarrere reported on a prospective study in which blood levels of cardiac troponin I were monitored for a year in 110 heart transplant patients.
     Dr. Labarrere says that in heart transplant recipients, "there is a form of CAD that progresses very fast." Instead of taking 40 years to develop, transplant CAD develops in only 1 or 2 years. Early after transplant "patients may be having small heart attacks without feeling anything" because the nerves to the heart have been cut.
     "If patients are having small heart attacks, heart muscle cells begin to die. Once this happens, they release troponin I into the blood," he said. Measuring this protein is "superior to measuring other enzymes, such as creatine kinase MB, for detecting minor heart injuries."
     All patients had high troponin I levels immediately after transplant. In 54 patients, however, the protein levels fell to undetectable within one year. In the other 56 patients, troponin I levels remained high. These patients were at much higher risk for CAD and graft failure
     "Finding elevated cardiac troponin I in the blood is an independent risk factor that identifies recipients at high risk of developing CAD or graft failure," the investigators concluded.
 
Source: JAMA 2000;284:457-464

 Drug Lowers CAD After Transplant

July 6, 1999 - Heart transplant recipients who took a common anti-viral drug have less life-threatening CAD than untreated patients, according to a study by Stanford researchers. The drug - ganciclovir - is routinely used to control an infection that is harmless in most people, but can cause serious problems for transplant recipients.
     The researchers re-analysed data from a study of ganciclovir for treating CMV (cytomegalovirus) in transplant patients. They found that patients who received the drug were nearly 3 times less likely to suffer blockage of their coronary arteries. CAD is the leading cause of death for heart transplant recipients who have survived more then one year.
     Patients' troubles don't end after a successful heart transplant. Their new heart often develops dangerous plaque build-up in its arteries shortly after transplant. Studies have shown that at least half of patients develop this condition within 5 years after heart transplant. Although the exact reason is unknown, studies have shown a link between infection with CMV and CAD in transplanted hearts.
     CMV is a member of the herpes virus family and is commonly acquired in early childhood. It can remain unnoticed in the body, often causing no effect at all. Recent studies have shown that the virus can hide in the smooth muscle cells of the heart during these latent periods, then is passed along with the heart when it is transplanted.
     When the body's immune system is weakened, either by illness or by anti-rejection drugs, CMV may come out of hiding. In severe cases, active CMV can be life threatening. The virus multiplies fast, affecting multiple organs, and resulting in pneumonia, blindness or fatal infections.
     The anti-viral drug ganciclovir was first tested in the early 1990s to prevent CMV illness in heart transplant recipients. Ganciclovir slows the spread of the virus by interfering with the protein that produces virus DNA. Patients were given the drug or a placebo right after surgery and for 28 more days. Ganciclovir-treated patients with CMV were much less likely to develop CMV illness during the first year of follow-up. The results of the study were published in the New England Journal of Medicine in 1992.
     In addition to causing CMV illness, CMV stimulates infected cells to multiply. When these cells are in the artery walls, that cell accumulation can block arteries. Because of the relationship between CMV and CAD in transplanted hearts, researchers wondered if ganciclovir could also protect against plaque build-up. They analysed the previous study, this time studying the patients by the presence or absence of CAD during the 4 to 7 year follow-up.
     Ganciclovir treatment appeared protective, especially among patients who were not taking a calcium channel blocker. Although most patients were taking calcium channel blockers for another reason, the drug has since been shown to protect against plaque build-up. When the researchers compared different risks in heart transplant recipients, the lack of ganciclovir treatment right after surgery was the biggest danger factor, increasing risk of CAD nearly 300%.

 Using Both CellCept And Tacrolimus

February, 1999 - We tested the effectiveness and safety of using both tacrolimus and MMF (mycophenolate mofetil or CellCept) to prevent heart transplant rejection. Forty-five patients were enrolled - 15 into Phase I and 30 to Phase II of the study. Intravenous tacrolimus was given for 2 to 3 days before switching to oral drugs. Target blood levels were 10 to 15 ng/mL. Treatment also included steroids and MMF.
     During Phase I, a dose of 2g/day of MMF was given. In Phase II, doses were adjusted according to MPA (mycophenolic acid) levels in the blood, with target levels of 2.5 to 4.5 micrograms/mL. Average follow-up was 696 days in Phase I and 436 days for Phase II.
     No patients died during Phase I. Rejection was diagnosed in 67% of patients. It seems that MPA blood levels greater than 3 micrograms/mL prevent rejection. During Phase II, one patient died. Rejection was seen in 10% of patients. Steroids were successfully withdrawn from all patients who completed 6 months' treatment.
     Combination therapy with tacrolimus and MMF is effective for preventing rejection in heart transplant patients, but routine drug level monitoring is critical.
 
Title: Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation: importance of mycophenolic acid therapeutic drug monitoring
Authors: Meiser BM, Pfeiffer M, Schmidt D, Reichenspurner H, Ueberfuhr P, Paulus D, von Scheidt W, Kreuzer E, Seidel D, Reichart B
Source: J Heart Lung Transplant 1999 Feb;18(2):143-9
PMID: 10194038, UI: 99208381

 New Immunosuppressive Med Works

July 14, 1998 - A new drug for preventing organ rejection called Rapamune (sirolimus/rapamycin) improves kidney transplant survival. "For the first time since cyclosporin was first used 15 years ago, we have clearly shown an anti-rejection drug to improve graft survival," said Dr. Barry Kahan. The largest single group of patients being listed for transplants are those with previously failed transplants.
     Phase 3 trials compared Rapamune at 2mg per day and 5mg per day to azathioprine plus cyclosporin plus prednisone, in kidney transplant patients. Seven hunded and nineteen kidney transplant patients participated in the randomized, double-blinded trial.
     Graft loss was lowest among patients taking the lower 2mg per day dose; only 2% of those patients lost an organ, while 6% of patients in the control group lost an organ. Patients treated with Rapamune showed 60 to 70% less acute rejection. Only 10% of the 5mg per day patients and 15% of the 2mg per day patients had acute rejection episodes, compared to 24% of patients taking standard meds. Rapamune also reduced the need for antibody therapy to reverse rejection episodes. Antibody therapy is costly and can cause other complications.
     Anti-rejection drugs cause serious complications, including serious infections and greatly increased risk of cancers. These drugs also cause kidney and nervous system toxicity. Many of the toxic side effects of cyclosporin are caused by the way in which it acts, inhibiting calcineurin activity in non-immune cells. Rapamune works in a different way to selectively block T-cells, which are part of the body's immune response. Because of the way it works, Rapamune does not affect calcineurin - this may mean fewer side effects.
     Rapamune is made materials found in the the soil of Easter Island. Further studies are underway.
 
Source: The University of Texas-Houston Health Science Center
Contact: Sandra Henry, 713-500-3308, or Jackie Loeb, 212-880-5270

 Lung Capability Worsens After Transplant

January 9, 2001 - The lungs are less able to distribute carbon monoxide after heart transplant, and this may make exercising harder. Dr. Omar Al-Rawas studied how this affected exercise ability in 26 heart transplant recipients.
     Before transplant, lung-diffusing capacity for carbon monoxide in these patients was lower than normal. After transplant, this capacity went down even more insatead of improving: from 73% of predicted to 60% of predicted. Although response to exercise improved, this lung capacity stayed much lower than normal in transplant recipients.
     After transplant this lung-diffusing capacity was directly related to Vo2max. This lung-diffusing capacity was not related to heart function. The researchers say this likely shows a general problem with the lungs' gas exchange system after heart transplant.
 
Source: Chest 2000;118:1661-1670

 Cyclosporin Use Encourages Cancer

February 11, 1999 - Increased risk of cancer from cyclosporine use may result from a direct effect on cells, not just from suppressing the immune system. "The high rate of cancer and its aggressive spread in people taking immunosuppressive drugs are thought to be from the weakened immune system," Dr. Minoru Hojo explained in the February 11, 1999 issue of Nature. He shows for the first time that cyclosporine also acts through TGF-beta (transforming growth factor-beta) directly on tumor cells to encourage tumor growth.
     In lab research, cyclosporine causes "striking changes in cell structure, including many cell protrusions, increased cell motion, and invasive growth" in a variety of tumor cells, the scientists say. Cyclosporine-caused TGF-beta production is the villain.
     In a related article, Dr. Gary Nabel notes that several questions remain unanswered. For instance, "we do not know whether cyclosporine has a similar effect on pre-cancerous cells, or whether it helps convert cells from benign to cancerous."
 
Title: Cyclosporine Promotes Tumor Growth, Progression Via TGF-beta
Source: Nature 1999;397:471-472,530-534

 Cyclosporin-induced High BP

August 21, 2000 - Researchers have found one way that cyclosporine causes high blood pressure. Dr. Ronald Victor says, "This discovery involves a protein in sensory nerves of the kidney," he said. "By understanding how this works, maybe we can develop new drugs that block the bad effects of cyclosporine on blood pressure."
     Victor used genetically altered mice to spot molecules in sensory nerves that let the nerves sense cyclosporine. When mice lacked a family of proteins called synapsins, their blood pressure did not go up when cyclosporine was given.
     Cyclosporine greatly improves long-term survival of heart transplant patients, but it causes serious high blood pressure. About 90% of heart-transplant patients develop cyclosporine-induced high blood pressure. The drug causes the nervous system to stimulate nerves, causing blood vessels to contract, increasing blood pressure.
 
Source: Proc Natl Acad Sci U S A. 2000;97(17):9765-9770

 Transplant Patients Get Skin Cancers

April 16, 1999 - People who have a heart or lung transplant are at risk for developing aggressive skin cancers, which can be fatal, says an Australian study. Immune-system suppressing drugs that stop organ rejection increase their risk for cancer.
     Of 619 people who had a heart, lung or heart/lung transplant, 11% (66) developed skin cancer sometime after the procedure, including 27 diagnosed with aggressive skin cancer. Eight of the patients developed melanoma, a type of skin cancer that is very dangerous.
     At the end of the 11 year study, 13 of the patients with skin cancer had died. All but one of these patients died from their cancer. The patients were an average age of 44 when they had their transplant. The patients developed skin cancer anywhere from 8 months to 10 years after receiving their transplants.
     "Standard treatment for cancer fails to control disease in a significant proportion of patients," the authors say.
 
Source: Cancer 1999;85:1758-1764

 Total Suppression Not The Key

November 2, 1999 - Tests in mice show what a way to help prevent transplanted organs from being rejected. Researchers found a combination of drugs that singled out activated T-cells and prevented them from multiplying. Many of the cells then died in a type of cell suicide called apoptosis.
     Blocking the activated cells which attack a transplanted organ without shutting down the rest of the immune system allows the body to learn to tolerate the transplant and still defend itself against germs, explained Dr. Laurence Turka.
     Under normal circumstances, T-cells are vital in fighting off infections. Activated by the presence of invaders, they attack and destroy germs. However, they also identify transplanted organs as foreign tissue and attack them, causing the body to reject the organ. The drug cyclosporin is used to suppress the immune system but it must be taken for life and has serious side effects.
     The researchers gave mice a combination of drugs - MR1 and CTLA4Ig - which they called a "co-stimulation blockade." The drugs weren't always effective but when cyclosporin was added, the result was "incredibly potent immunosuppression," explained Dr. Terry Strom.
     That didn't allow the body to build up tolerance for the transplant. "When this combination of drugs is stopped, the recipient acts as if it is a fresh transplant. Everything just breaks loose all over again," Strom said. "The lesson is that maximum immunosuppression is not the way to get tolerance," he stressed.
     So the team tried combining the co-stimulation blockers with another drug - rapamycin - instead of cyclosporine. Rapamycin blocked the proliferation of activated T-cells, but it didn't block cell death. Dr. Strom believes that additional drugs should be developed and used together. "For tolerance to develop, it's not the size of the immune response but the type of immune response that counts."
     "We believe what happens is you've weakened one part of the immune system, and the cells commit a form of mass but not quite total suicide," he explained. That tips the balance to reduce rejection, while allowing the body to develop a tolerance for the new organ. "One of the nice things is that it only affects the activated cells," Turka said, so the rest of the immune system remains intact to fight off new attacks. The treatment has not been tested in larger animals.
     In another article, Dr. Hans Schlitt reported that the presence of some donor leukocytes (white blood cells) in transplanted tissue is essential to graft acceptance. Rats whose transplanted hearts were treated to destroy all donor leukocytes rejected those transplants, while rats whose transplanted hearts still had some donor leukocytes experienced long-term transplant survival.
 
Source: Nature Med 1999;5:1303-1307,1298-1302,1292-1297,1231-1232,1245-1248

 UNOS Posts Transplant Organ Info

September 10, 1999 - UNOS says it will immediately start posting organ availability on a secure web site that can be accessed only by transplant surgeons and organ procurement officers. The goal is to speed up matches between organs and patients in need.
     Also, UNOS will publish statistics on waiting times and transplant results on a separate web site just for patients, allowing them to compare hospitals in their area. Among other things, the consumer site at www.transplantliving.org/ will show transplant recipient survival rates at 6 months, one year, and 3 years. Previously, the most current data was for 1994, which was just ridiculous! The site will also show how long patients at each center wait for transplants.
     A separate database called UNET will be accessible only to healthcare professionals and transplant coordinators. In that system, a coordinator will be able to tell UNET an organ is available and check regional waiting lists for appropriate patient matches. UNET will eliminate paperwork and phone calls, and hopefully speed up the transplant process.
 
Source: Reuters Health

 Recycling Used Hearts

At age 67, with a failing heart, Jim Shirley appeared to be a goner. He's alive today thanks to a heart program at UCLA. "Up to one third of people waiting on the heart transplant list die before getting a heart," explained UCLA cardiologist Jon Kobashigawa. "There was a very large, untapped pool of older donors who had fine hearts. So the idea was, why not use these older donor hearts for older recipients?"
     Mr. Shirley received a heart from a 52 year old man. The heart's arteries were slightly clogged and doctors say it normally would have been discarded - but a year later, it's still beating in Shirley. After his annual checkup, the old cowboy was given a clean bill of health. Doctors at the UCLA Medical Center say the "alternative donor program" using imperfect hearts of older donors, could increase the availability of donor hearts by 10%. "His heart is beating normally and is providing him with enough blood flow to let him to do all the activities he used to do, including horseback riding."
     Well, almost everything. "I can't chase women. I can't drink whiskey. I can't go out and move around like I used to," admitted Shirley. But he's back to riding a bulldozer and that's just fine with him. "I feel like a new man," Shirley says.
 
From: The LA Times

 Making More Hearts Available

November 20, 2000 - Less than perfect hearts from older donors can be successfully used for older patients, UCLA transplant surgeons said at the annual meeting of the American Heart Association.
     At UCLA, patients younger than 65 are placed on the standard heart transplant waiting list. Those older than 70 are placed on an alternate list, to receive hearts from older donors. Those between the ages of 65 and 70 can choose which list they want to be on. Dr. Daniel Marelli said that many of these patients choose the alternate list, so younger patients can get the younger hearts.
     Transplant results with the older hearts in older patients have been good, with a lot of improvement in quality of life, Dr. Marelli reported. He reviewed 175 patient cases age 62 or older, 54 of whom were placed on the alternate list. For those on the standard list, survival was 92% at 30 days and 72% at 5 years. For those getting older hearts, survival was 90% at 30 days and 78% at 4 years.
 
Source: Reuters Health

 Xenotransplantees Can't Donate Blood

January 14, 2000 - An FDA committee has recommended that people who have had live animal tissue or cell transplants should never be allowed to donate blood or plasma products. Blood and plasma already donated by xenotransplant recipients should be recalled and destroyed, said the members of the Xenotransplantation Subcommittee of the Biological Response Modifiers Advisory Committee. Xenotransplantation means transplants of non-human tissue into humans.
     Most of the advisors also agreed that people who have had "intimate contact" with xenotransplant recipients should not give blood or plasma either. The FDA proposed adding 3 questions about xenotransplants to the 32-question donor screen already in use. The concern is that people receiving or being exposed to animal tissues might transmit pathogens such as porcine endogenous retrovirus through their blood.
     If the new blood donation policy is adopted, it would apply only to a small number of actual transplant recipients. Only about 50 people have had animal tissues or organs directly transplanted into their bodies. But at least 700 others have had their own cells or tissues augmented outside their bodies with animal cells or tissues, FDA's Jay Siegel says. "The numbers are likely to grow" as research accelerates, said Siegel.
     The FDA has already expanded the definition of xenotransplant to include any procedure involving the transplant, implant, or infusion into humans of live cells, tissues, or organs from a nonhuman animal source; or human body fluids, cells, tissues or organs that had contact with live, nonhuman animal cells, tissues or organs.
 
Source: Reuters Health

 Xenotransplant Looking Less Likely

February 9, 2001 - Serious doubts about successful pig-to-human organ transplants have been expressed by a government expert advisory committee. Several companies, including Britain's PPL, Switzerland's Novartis and America's Biotransplant, have been backing xenotransplant research, hoping that animal organs could supplement human donor organs.
     Chances of success may be getting slimmer, according to the annual report of the UK Xenotransplantation Regulatory Authority. The report notes that genetic modification of donor animals - to remove the gene that causes hyperacute rejection and to add genes to stop later rejection - is only in the "very early stages."
     It adds that, "Survival times in animals (primates) do not provide any proof that xenotransplanted organs can sustain life in humans. ... The absence of data is a concern." The report also notes that it is probably impossible to eliminate all possible risk of transferring infectious agents through xenotransplantation. "Moreover, the possibility of seeing previously unrecognised organisms has to be kept in mind."
     The report concludes, "It seems that xenotransplant - particularly for heart transplant - being available anytime soon is unlikely."
 
Source:Reuters Health

 Taking Iron Changes Cellcept Level

February 1, 2001 - Taking both Cellcept and iron-ion preparations - both commonly given to transplant recipients - should be avoided. Taking both lowers Cellcept absorption a lot, according to a new report.
     In the first phase of the trial, Dr. Kazuyuki Ueno gave 7 volunteers one gram of Cellcept. Then after a 7-day washout period, the patients took one gram of Cellcept and 2 tablets of iron ion preparation. In each study phase Dr. Kazuyuki measured Cellcept blood levels.
     The researchers say that blood levels of the anti-rejection drug were greatly reduced during the trial's second phase. During the first phase, the average area under the curve per hour was 32.9 µ/mL versus 2.92 µ/mL during the second phase.
     Peak Cellcept levels were also much lower during the study's second phase. Average peak drug level per hour during the first phase was 20.1 µg/mL versus 1.30 µ/mL in the second phase. (Jon's note: that's a huge difference!)
 
Source: Clin Pharmacol Ther 2000;68:613-616.

 Virus May Promote Organ Rejection

May 17, 2001 - A common virus of the heart is a major reason for heart transplant failure in children, say researchers at Baylor College of Medicine. The discovery was reported in the May 17 issue of the New England Journal of Medicine. The study concludes that frequent biopsies are the best way to identify the virus.
     The research team, led by Towbin and Bowles, has been studying heart transplant failure in children for 10 years. "The bane of all transplant doctors is the development of coronary artery disease in transplant patients. It leads to either sudden death or the need for re-transplant," said Towbin.
     The team studied 553 biopsies from 149 transplant recipients, from newborns to 18 year olds, over a 5 year period. The biopsies were tested for common viral infections. Results showed that 85 percent of the patients who at some point tested positive suffered an adverse event within 3 months of that result.
     "The infection isn't there at transplant ... suddenly it's just there," Towbin said. It may be from an upper respiratory illness. In most cases the infection appeared more than two years after transplant.
     When the heart shows signs of rejection the treatment is more steroids and immunosuppresent drugs. However, this does not affect the virus, which may still be sitting there to create rejection again and again. Towbin and Bowles said their discovery suggests that all heart recipients should be biopsied routinely with PCR testing done every time.
 
Source: Baylor College of Medicine
Contact person: Lori Williams - loriw@bcm.tmc.edu

 Kids Need Monitoring Longer

February 28, 2000 - Heart biopsies to test for rejection should be done on a regular basis for pediatric patients longer than 2 years after their heart transplant, even if the patients do not show rejection symptoms.
     Dr. Clifford Chin reviewed 481 heart biopsies taken from 44 patients two years or more after they had a heart transplant. The authors note that "of the positive rejection episodes, 75% occurred in patients without symptoms."
     "Although rejection is uncommon in pediatric patients more than 2 years after transplant, episodes of treatable rejection can happen without any symptoms," Dr. Chin's group concludes. "Surveillance biopsies lead to quicker detection of high-grade rejection so therapy can be started to avoid progression and all of its complications and mortality."
 
Source: J Pediatr 2000;136:238-242

 Mis-Matching Blood Types In Babies

March 14, 2001 - Dr. Lori West has transplanted a donor heart into a 2 week old boy, where the donor had a different blood type. Although blood types should match, Dr. West hoped that the immature immune systems of babies would tolerate hearts from non-matching donors. In adults, doing so would cause the new heart to clot and stop in minutes.
     Ten transplants and 5 years later, she and her colleagues are reporting a survival rate of 80%, which equals the rate using matched blood types. The doctors transplanted hearts of mis-matching blood type into 10 infants with failing hearts. The children - who were as old as 14 months - almost all had type O blood. In most, their immune systems were not yet producing antibodies against other blood types.
     Many children, especially with type O blood, die waiting for a matching heart. Type O babies are compatible only with type O donors. Recipients with A, B and AB blood can be matched with at least 2 other types. Eight of the 10 patients survived in this study, which followed them for up to 5 years. Two died, but the causes seem unrelated to blood type.
     "I think there is enough evidence to say this is safe to do in babies, providing that they don't have the antibodies," West said. Babies usually develop antibodies to incompatible blood at 6 to 14 months of age. However, Dr. Mark Boucek, who wrote an accompanying editorial, said such experiments should be duplicated before the practice is accepted as standard.
 
Source: The Associated Press

 St. John's Wort And Cyclosporine

February 16, 2000 - Swiss researchers have reported 2 cases of acute heart transplant rejection from an interaction between St. John's wort and cyclosporine.
     Dr. Georg Noll reports a 61 year old patient who had a heart transplant 11 months before being admitted for a heart biopsy. The patient had been on 125mg cyclosporine twice a day, 100mg azathioprine daily and 7.5mg prednisone daily. The patient started treating himself for depression with 300mg St. John's wort 3 times a day, about 3 weeks before being admitted.
     Upon admission, Dr. Noll noticed low cyclosporine blood levels. The biopsy showed acute organ rejection, and the doctors suspended the St. John's wort. Noll's group tried mildly increasing the man's meds but another heart biopsy showed that the acute rejection persisted. At this point, they took serious drug action, which stopped the rejection episode.
     One week later, a 63 year old patient was admitted to the hospital, also for heart biopsy. This patient had undergone heart transplant 20 months earlier and had been maintained on the same three anti-rejection drugs. Three weeks before admission, a psychiatrist started the patient on 300mg St. John's wort 3 times a day because of anxiety and depression. This patient also had a low cyclosporine level and his biopsy also showed acute organ rejection.
     Dr. Noll halted the St. John's wort, and cyclosporine levels increased to the proper level. The researchers believe that St. John's wort caused the drop in blood levels of cyclosporine, leading to rejection. They point out that St. John's wort extracts contain naphtodiantrons, which alter the way a human body metabolizes cyclosporine.
 
Source: Lancet 2000;355:548-549

 Hope For Recipients With High Pulmonary Pressures

June 17, 2000 - Yale University researchers have developed an experimental heart transplant surgery that spares the right ventricle. This may benefit patients with pulmonary hypertension. "We believe the technique holds promise for the dilemma of heart transplant in the face of high pulmonary pressures," says a research team led by Dr. John Elefteriades.
     The researchers point out that right heart failure remains the leading cause of early death following heart transplant, since the donor right ventricle is not used to high pulmonary artery pressure. "If it were possible to preserve the conditioned right ventricle of the recipient, while replacing the weak and enlarged left ventricle, this could be of great benefit," they say.
     Dr. Elefteriades successfully did a right ventricle-sparing transplant surgery in 4 dogs, which is detailed in the journal. In each case, the left ventricle was removed and bleeding was easily controlled. Stable heart rhythm was maintained in the recipient right heart of all 4 animals. All were removed from the heart-lung bypass machine without any serious complications. After removal, the average arterial blood pressure ranged from 60 to 110 mm Hg.
     "These experiments show that such a technique is feasible," the authors conclude.
 
Source: Ann Thorac Surg 2000;69:1858-1864

 Blood Test May Spot Rejection

April 15, 2002 - Two recent studies suggest that a blood test called an "enzyme linked immunosorbent assay" - or ELISA - can spot heart recipients at risk for rejection. Dr. Adriana Zeevi - part of both studies - said, "This is an easy, risk-free blood screening test." The ELISA detects HLA antibodies
     In one study, blood samples taken within 30 days before transplant in 36 pediatric heart transplant patients were tested. ELISA tests were positive in 10 of them. Five of these patients developed severe rejection, compared to only 3 of 26 ELISA-negative patients.
     Similar results were seen in a study of 75 adult lung transplant recipients. Six of the 14 with a positive ELISA developed persistent acute rejection compared to only 9 of 61 negative patients. Dr. Zeevi said, "If we know ahead of time who is at risk for rejection, we can customize therapies to prevent rejection."
 
Source: Reuters Health
From: The 22nd Annual Scientific Sessions of the International Society for Heart and Lung Transplantation

 Vitamins Help After Transplant

March 28, 2002 - Antioxidant vitamins like vitamins C or E may help heart transplant patients keep their arteries clear, says a new study. At least 70% of heart recipients develop artery blockages within 3 years. This transplant-related atherosclerosis is one of the biggest threats to survival for these patients. The study found that daily vitamin C and E slowed the growth of plaque in artery walls for up to a year after transplant.
     Forty patients within 2 years of their transplant surgery took either 500mg vitamin C plus 400 IU vitamin E twice a day (19 patients), or placebo (21 patients) for one year. Primary end point was the change in blood vessel openness as measured by intravascular ultrasound. Vitamin C and E blood levels were also measured at study start and at one year follow-up. All patients also took the cholesterol-lowering drug pravastatin.
     Vitamin C and E levels increased in the vitamin group but did not change in the placebo group. During the one year of treatment, blood vessel openness went down in the placebo group by 8% but did not change in the treatment group.
     More study is needed to see if the benefits of vitamin C and E lasts over several years, when most cases of transplant-related CAD occur.
 
Title: Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial
Authors: James Fang, Scott Kinlay, John Beltrame, Hiroyuki Hikiti, Marco Wainstein, Dominik Behrendt, Jung Suh, Balz Frei, Gilbert Mudge, Andrew Selwyn, Peter Ganz
E-mail: jfang@partners.org
Source: Lancet 2002; 359: 1108-13

 Testosterone May Spur Rejection

April, 2002 - Hormone therapy with leuprolide acetate (Lupron) is often used to treat prostate cancer. Testosterone supplements are often used in adult men with reduced sex drive or impotence, and low blood testosterone level. Although these hormone therapies are generally safe, we have seen 3 cases of acute heart rejection linked to use of these drugs in men who have had a heart transplant.
 
Title: Hormone therapy in men and risk of cardiac allograft rejection
Authors: Schofield RS, Hill JA, McGinn CJ, Aranda JM
Source: J Heart Lung Transplant 2002 Apr;21(4):493-5
PMID: 11927227

Donor Bone Marrow Cells Help Transplant 

June 4, 2003 - Children who receive bone marrow cells from the organ donor during heart transplant have less acute rejection after 6 months than other heart recipients. Bone marrow cells are injected into several areas of the thymus before the chest is closed during transplant surgery.
     Dr. Steven Webber presented findings from the first 14 children to get "intrathymic" bone marrow. Average age at surgery was 7-1/2 years. These 14 young patients were compared to 23 matched controls who had standard heart transplant. Average follow-up was 30 months.
     Risk of acute rejection was the same in both groups for the first 6 months after surgery. However, longer follow-up showed that rejection happened less often in the group that got donor bone marrow.
     One child who received this therapy died of lymph cancer at 6 months. One control patient died of chronic rejection at 8 months. The rest are alive and well, according to Dr. Webber. There have been no cases of speeded-up rejection, over-sensitivity in the body, or graft-versus-host disease in the study group. Infection rates were the same in both groups.
     Between 6 and 12 months, there was one case of acute rejection in the marrow group versus 6 episodes in the control group. One year and longer after transplant, there were 2 cases of rejection in the 13 remaining marrow patients versus 20 cases in the remaining 22 control patients.
     No adverse events have been seen yet. The next step is to reduce anti-rejection drug use over time to see what happens. Researchers will also use monoclonal antibodies to reduce T cells in recipients before transplant.
     Dr. Joren Madsen said, "This is the first try to induce tolerance in a human heart transplant setting ... We need to start taking anti-rejection drugs away and we need to prove that tolerance has occurred. We have no test to prove that. We're flying by the seat of our pants."
 
Source: Martha Kerr on ATC 2003: Abstract 62. Presented 06-01-03.


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, 2006 Jon C.

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