FDA clears test to help patients with kidney transplants

The U.S. Food and Drug Administration today announced that it has cleared a test to help manage potential organ rejection in kidney transplant patients. The test, called QMS Everolimus Immunoassay, monitors the blood level of everolimus, a drug that helps prevent rejection in kidney transplants.

Everolimus, marketed under the trade name Zortress, was approved by FDA in April 2010 for use in adult kidney transplant patients who are at low-to-moderate immunologic risk.

Transplant patients are routinely given drugs that suppress the immune system (immunosuppressants) such as a regimen containing everolimus, cyclosporine, basiliximab, and corticosteroids. These drugs help prevent organ rejection, which occurs when the body’s immune system attacks and destroys a transplanted organ.

Some immunosuppressants are associated with toxic side effects that can injure transplanted kidneys. Balancing the levels of immunosuppressants is critical since transplant patients must take these drugs for the rest of their lives.

“QMS Everolimus is the first FDA-cleared test physicians can use to maintain appropriate levels of the immunosuppressant everolimus,” said Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health.

QMS Everolimus is one of a number of FDA-cleared or -approved tests physicians can use to monitor and manage immunosuppressant levels, including tests for cyclosporine, tacrolimus, and sirolimus. These tests, along with careful monitoring of clinical signs and symptoms of organ rejection, tissue biopsies, and other lab tests, may increase the chance of having a successful transplant and possibly extend the survival of a transplanted kidney.

In addition to other evaluations, Thermofisher, the manufacturer of QMS Everolimus, demonstrated the performance of the test by comparing results from the new test to the results from everolimus reference tests used in the clinical trial of everolimus. When the clinical trial blood samples were tested with QMS Everolimus, the results, on average, were similar to those of the clinical trial reference test.

More than 87,000 patients are awaiting a kidney transplant in the United States, according to the Health Resources and Services Administration’s Organ Procurement and Transplantation Network.

QMS Everolimus is manufactured by Waltham, Mass.-based Thermofisher. Zortress is marketed by East Hanover, N.J.-based Novartis.

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Chronic Health Conditions Common for Stem Cell Transplant Survivors

/PRNewswire/ -- Although hematopoietic cell transplantation (HCT) cures many blood diseases, two-thirds of long-term survivors report at least one chronic health condition after the procedure, according to a recent study published online in Blood, the journal of the American Society of Hematology. Overall, these patients were three and a half times more likely to develop a severe or life-threatening health condition, such as cardiovascular, endocrine, or musculoskeletal problems, as well as new cancers, when compared with their cancer-free siblings.

"Although hematopoietic cell transplants have helped thousands of patients survive cancer, the burden of chronic illnesses borne by these survivors is substantial," said senior study author Smita Bhatia, MD, MPH, professor and Ruth Ziegler Chair in Population Sciences at City of Hope Comprehensive Cancer Center in Duarte, CA. "We hope the results of this study build awareness of the problem to help ensure a continued high quality of life among transplant survivors through life-long follow-up and proactive care."

It is estimated that more than 45,000 patients undergo HCTs each year to combat life-threatening diseases such as leukemia, lymphoma, and aplastic anemia. The procedure restores blood-forming cells in the patient's bone marrow that have been destroyed by anti-cancer treatments, such as chemotherapy. Although previous studies have shown that more than 70 percent of those who survive the first two years after HCT are expected to become long-term survivors, the elimination of the cancer has not always led to a full restoration of health. The high-intensity chemo- and radiotherapies needed prior to transplantation can damage many organs and have a negative impact on the overall health of HCT survivors.

The researchers for this study examined the prevalence and severity of chronic health conditions reported by 1,022 HCT survivors who received their transplants at City of Hope or the University of Minnesota between 1974 and 1998 for a blood cancer or severe aplastic anemia. The results were compared to those of 309 siblings of the participants. Each of the HCT survivors and siblings completed a questionnaire, which included questions regarding physical health conditions, access to and use of medical care, and sociodemographic characteristics.

The results showed that chronic health conditions were widespread in the HCT survivors. Sixty-six percent of these patients reported at least one chronic condition, half reported at least two chronic health conditions, and more than a third (35 percent) reported three or more conditions. In comparison, 39 percent of the siblings reported at least one chronic health condition, but only 15 percent had two or more conditions, and 6 percent had three or more. A severity score of grade 1 (mild) through 4 (life-threatening) was also assigned to each health condition. Mild and moderate conditions include ocular issues, hearing impairment, hypertension, and sensory problems while severe conditions include cardiovascular, gastrointestinal, and muscuskeletal problems, as well as new malignancies. In the HCT cohort, 18 percent reported conditions of the severest level (grade 3 or 4), while only 8 percent of the sibling group had grade 3 or 4 conditions.

Additionally, 53 percent of the HCT survivors who had received grafts from a donor experienced chronic graft-versus-host disease (GVHD), a complication in which the foreign transplanted cells attack the cells in the recipient's body. Although GVHD is treatable, this complication contributed significantly to the increased risk of multiple severe or life-threatening conditions in these patients. Among the survivors with GVHD, nearly one-quarter had severe or life-threatening conditions such as cardiovascular and gastrointestinal disorders, and more than half had two or more health conditions.

The researchers concluded that HCT survivors have a high rate of illness due to chronic health conditions, especially those with chronic GVHD, and recommended that health-care providers conduct systematic and targeted follow-up of these high-risk patients.

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House, Senate Put Forth Legislation to Renew Funding, Bolster Nation's Bone Marrow and Umbilical Cord Program

/PRNewswire/ -- The National Marrow Donor Program® (NMDP) today applauded the introduction of the "Stem Cell Therapeutic and Research Reauthorization Act of 2010." Sens. Orrin Hatch (R-UT), Christopher Dodd (D-CT), Richard Burr (R-NC), Jack Reed (D-RI), John Ensign (R-NV), and Al Franken (D-MN) introduced the act in the U.S. Senate as S. 3751 on Thursday, Aug. 5. Last evening, Reps. C.W. Bill Young (R-FL) and Doris Matsui (D-CA) introduced the companion legislation, (H.R. 6081), in the House. This legislation seeks to reauthorize the C.W. Bill Young Cell Transplantation Program (National Program) and the National Cord Blood Inventory (NCBI). These programs must be reauthorized before the NCBI sunsets.

Last year 12,000 patients searched the national registry, publicly known as the Be The Match Registry®, for a marrow donor or umbilical cord blood unit. Congressional support of the National Program and the NCBI is critical to ensure all patients have access to transplant.

"I am pleased with the introduction of this legislation and continued bipartisan support," said Jeffrey W. Chell, M.D., chief executive officer of the NMDP. "The reauthorization will provide us with the opportunity to continue our efforts to increase the number of adult donors and umbilical cord blood units available through the National Program."

Since its inception in the mid-1980s, the NMDP has operated the National Program awarded via a competitive bid process administered by the Health Services Resources Administration (HSRA). Every day, the National Program helps thousands of patients with leukemia, certain lymphomas, and other life-threatening diseases find a matching donor or umbilical cord blood unit. For many of these patients, a transplant may be the best or only hope for a cure. To date, the NMDP has facilitated more than 40,000 transplants. This accomplishment would not have been possible without the ongoing, sustained support of Congress and its efforts to increase unrelated marrow and cord blood transplants in the United States.

The proposed legislation demonstrates the continued federal commitment to these programs and recognizes the importance of providing patients and physicians with a single point of access to marrow and cord blood units that can be used for transplant. It also addresses the importance of building a diverse registry of marrow donors and cord blood units. Additionally, the legislation includes modifications necessary to continue the successful work of these programs.

The NMDP applauds the hard work and dedication of Congress to produce a bipartisan and fiscally responsible bill that will assist the NMDP in advancing its life-saving mission. The NMDP looks forward to working with Congress, and its network partners in the transplant community including, physicians, cord blood banks, donors, patients, and their families, to gain additional support for continued success of cellular transplantation.

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Piedmont Hospital’s Transplant Services Continues to Enhance Patient Care By Launching Satellite Offices throughout Georgia

Piedmont Hospital Brings Dalton Its First Transplant Clinic

Piedmont Hospital Transplant Services is pleased to announce the opening of a new satellite transplant clinic in Dalton, Ga., on Friday, October 23. This facility will support continued efforts to enhance patient access to transplantation evaluation and follow-up care with strategically located satellite clinics throughout the state of Georgia.

These area clinics will make access to care more convenient for those patients who live long distances from Piedmont Hospital in Atlanta and reduce the initial evaluation time for kidney transplant candidates from two days to one.

“We are pleased and privileged to bring Dalton its first transplant clinic, increasing access to services for transplant patients across north Georgia and southeastern Tennessee,” said Mark Johnson, M.D., program director of Piedmont’s Transplant Services. “This clinic will provide pre- and post-transplant care to end-stage kidney and pancreas patients.”

Piedmont’s first satellite clinic opened in Savannah, Ga., in December 2007, and a second clinic opened in Albany, Ga., in February 2009. Each clinic offers education classes for those interested in the advantages and risks of transplantation, provides extensive information about the costs of post-transplant medication and how one can plan to meet those costs. Initial candidate screenings will be performed by a transplant physician and/or nurse specialist, allowing patients with potential disqualifying issues to take corrective action before making an appointment for a full evaluation at the Piedmont Hospital Mason Transplant Clinic in Atlanta.

Piedmont Hospital has one of only two adult liver transplant programs and one of three kidney/pancreas transplant programs in Georgia.

The new satellite transplant clinic in Dalton is located at 1109 Burleyson Road, Suite 101 Dalton, GA 30720, and will initially offer services for those with kidney and pancreas disease. For more information on the Piedmont Hospital Transplant Services Dalton Satellite Clinic, call 888-605-5888.
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FDA Clears Test to Help Doctors Manage Heart Transplant Patients

The U.S. Food and Drug Administration today announced it has cleared for marketing a non-invasive test that uses molecular expression techniques to assist doctors in managing heart transplant patients post-surgery for potential organ rejection.

"AlloMap can help contribute to an appropriate treatment plan by identifying those patients not experiencing post-operative heart transplant rejection," said Daniel G. Schultz, M.D., director of the FDA's Center for Devices and Radiological Health. "It is an example of how advancements in science and technology are leading to new medical care diagnostics."

AlloMap measures genetic information contained in the white blood cells (cells of the immune system that defend the body against invading viruses, bacteria or other foreign material) from a patient's blood sample.

Specifically the test measures gene expression—or how DNA transcribes its genetic instructions to RNA, the nucleic acid that translates and carries out those instructions—of 20 different genes, resulting in a score that indicates whether a heart transplant patient is unlikely to be rejecting the new organ.

Nearly every cell of the body contains a full set of chromosomes and identical genes but only a fraction of these genes are turned on or expressed in any given cell. Gene expression occurs when certain molecular information contained within DNA is transcribed to create molecules known as RNA. These molecules in turn make the proteins that perform most of the critical functions of cells.

Following a heart transplant, physicians regularly monitor patients for transplant rejection, a significant risk to patient survival. Rejection occurs when the patient's immune system fails to accept the new organ and begins to attack it. Successful heart transplants depend on a balanced immune system response—a response that is suppressed enough to accept the new organ but strong enough to protect the patient from infections.

Clinicians often rely on heart biopsy to gauge whether a patient is rejecting the transplanted heart. However, biopsies are difficult to perform and can be risky for the patient.

According to the National Heart, Lung and Blood Institute, half of all possible rejections happen during the first six weeks after surgery and 25 percent of patients have signs of possible rejection at least once during the first year following a transplant.

XDx Inc. developed AlloMap using blood and biopsy samples and other information collected from heart transplant recipients at nine U.S. heart transplants centers participating in the Cardiac Allograft Rejection Gene expression Observational study (CARGO). CARGO provided data from 153 patients on 300 medical visits at various times after heart transplant study.

According to the American Heart Association, there were more than 2,000 heart transplants performed in the United States during 2006.

AlloMap is the third in vitro diagnostic multivariate index assay (IVDMIA) cleared by the FDA. IVDMIAs are medical devices that combine the values of multiple variables to yield a single, patient-specific result.

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Transplantation of Kidneys from Black Cardiac-Death Donors Provide Black Recipients with the Best Long-Term Survival

Contrary to prevailing assumptions, Johns Hopkins researchers have shown that kidneys recovered from black donors who died from cardiac death offer the best survival rate for black recipients of a deceased-donor kidney.

This discovery, released online this week and appearing in the October 2008 issue of the Journal of the American Society of Nephrology, challenges the long-held belief that kidneys from white brain-death donors offers the best deceased-donor transplant survival rate for either black or white recipients.

“Our findings indicate that increased use of kidneys from cardiac-death donors could help reduce the organ shortage and improve outcomes for black kidney transplant recipients,” says lead author Jayme Locke, M.D., M.P.H., of the Department of Surgery at Johns Hopkins.

Locke and a team of Johns Hopkins researchers examined the outcomes of more than 25,000 black adults who received a deceased-donor kidney transplant between 1993 and 2006.

Results showed that black recipients who received a kidney from a black cardiac-death donor had a 70 percent reduction in the risk of kidney loss and a 59 percent reduction in risk for death when compared to black recipients who received a kidney from a white brain-death donor.

“Our data is consistent with the previous observation that black recipients seem to do better with kidneys from white brain-death donors than they do with kidneys from black brain-death donors or white cardiac-death donors, however, the fact that black recipients have the best outcomes with kidneys from black cardiac-death donors is significant,” says co-lead author Daniel Warren, Ph.D., of the Department of Surgery at Johns Hopkins.

He says that the exact mechanisms responsible for racial differences in outcomes after kidney transplantation are not known, however, the results suggest that the genetic background of the donor and recipient likely have a significant impact on long-term outcomes.

“We believe that an improved understanding of the molecular consequences of cardiac and brain death is critical to improving outcomes for all kidney transplant recipients and warrants further investigation,” he added.

There are currently more than 70,000 Americans waiting for kidney transplants. Only about 600 deceased-donor kidneys donated after cardiac death are currently used for transplantation versus 7,000 donated after brain death.

This discrepancy is due in part to the belief that kidneys that are exposed to cardiac death generally suffer more damage than kidneys that are exposed to brain death.

“Our results show this is not always true, and that is significant news for all patients waiting for a kidney,” says Locke.

Other researchers who worked on this study from Johns Hopkins include Robert Montgomery, M.D., Ph.D.; Andrew Cameron, M.D.; Joseph Melancon, M.D.; Dorry Segev, M.D.; Andrew Singer, M.D., Ph.D.; Christopher Simpkins, M.D., M.P.H.; Andrea Zachary, Ph.D.; Francesca Dominici, Ph.D.; Mary Leffell, Ph.D.; and Deborah McRann, B.S.N.

Louise Markert’s Little Schoolhouse

When the call came in late March, Louise Markert was ready. Across campus, through the hospital and into the operating room she marched. Nestled inside the sterile plastic container she held close to her body were precious slivers of a living human organ.

Those tiny slices held the promise of life for an innocent baby sleeping just beyond the operating doors. And Markert was the only doctor in the world who could deliver the experimental therapy they represent.

It was a similar phone call 16 years ago that brought Markert to these OR doors. She had been a pediatric immunologist on call when “I got a call about a baby in Knoxville, Tenn.,” she recalls in a staccato voice rounded by remnants of her northern New York origins. “The baby had DiGeorge syndrome and they wanted to know if we could help.”

DiGeorge syndrome is a quirk of nature that occurs when something goes terribly wrong during the first trimester of an embryo’s development. It sets the stage for a complicated disease and a host of maladies, including heart defects and calcium problems. In less than 1 percent of infants affected, a severe disruption of the immune system means almost certain death.

The Knoxville doctors had turned to Duke for help because of its leaders in clinical and basic immunology, including the late Bernard Amos, Rebecca Buckley and Barton Haynes. Among Duke’s notable achievements in this area was the tissue typing that led to the success of modern-day organ transplants.

Markert, who fell in love with immunology in high school, trained at Duke under Amos. “He recommended I do pediatrics. I didn’t like kids much at that time.” But that would soon change.

Markert eventually focused her efforts on the thymus. This vital but overlooked organ is located behind the breastbone and guides the immature white blood cells from the bone marrow so they can develop into T-cells that fight off infection.

“The thymus is like a schoolhouse,” Markert says simply, offering the analogy she uses with her patients. “When you open the doors, the students — in the form of immature white blood cells — are the children who run in. Eventually they graduate to be T-cells.”

Each year, fewer than 10 infants are born with complete DiGeorge, in which they lack a thymus entirely. Without the gland, babies have little to no chance of living past their second year.

Although thymus transplants had been attempted as early as the late 1960s for other immunodeficiency diseases, there had been little success, in part because no one knew which infants could benefit.

There also were concerns about the tissue’s viability. The thymus had to be harvested from a living donor and kept alive by being sliced into tiny pieces, which allows oxygen to reach all of the tissue’s cells while it’s being tested for safety prior to implant.

Pediatric heart surgeons routinely cut through the thymus to get to the heart, and it is normally discarded during open heart surgery on very young patients. That meant there was a fairly plentiful supply of the glands, but Markert keenly remembers her mounting frustration with keeping them viable for a transplant.

“I’d slice the tissue and after a week of culture, I’d bring it to Dr. Haynes’ lab where his technicians would section it. Then I’d go over to meet with Bart Haynes (an authority on T-cells and head of Duke’s human vaccine institute) who would tell me it was dead.”

Over and over again she tried. She learned how to sustain the thymus in a lab dish of special fluid and to slice it very gently. “That’s key,” she says. “If you use too much pressure, you kill the whole thing.”

Markert distinctly remembers the day when she arrived at Haynes’ door and learned that her persistence had paid off. “It was wonderful when he finally smiled and said, ‘It’s alive.’”

“The first transplant was so stressful, you can’t imagine. The child developed a horrible rash. I thought I had given her cancer. She was a real mess.”

The 3-month wait to biopsy that thymus seemed to take forever. Finally, she and Haynes peered into the microscope. “It looked like a normal thymus. It was unbelievable.”

Although that baby lived, complete success was not yet at hand. The next three babies died. By the time the fifth child survived, Markert was recognizing some of her missteps.

“We learned a lot about how to manage the children and do better.”

She also figured out why the first child developed the rash. “I run into it all the time. The child had developed rogue T-cells. Now I use cyclosporine (an anti-rejection drug) and have no problems.”

Today, that first baby is a healthy 14-year-old. And, after 52 transplants, Markert’s procedure now boosts a 73 percent success rate. Although still considered experimental, thymus transplants are covered by some insurance companies.

Markert receives funding from the National Institutes of Health and the Food and Drug Administration to continue the research. The amount of paperwork needed to track her program and continue its funding can feel insurmountable. Stacks of papers, files and folders consume her office, yet Markert remains committed. Her staff makes her work possible, and helps her field daily referrals from around the world.

She’s had highs when patients live, and lows when she thought her entire program would be put to a penniless death. But none of it has dampened Markert’s enthusiasm for what’s become her life’s passion.

“When I started, I was told I’d never get grants and that I should work with mice. I don’t really like mice,” she says matter-of-factly.

“Now I’m helping babies live who would die otherwise. That’s what’s important to me.”

Debbe Geiger is a senior media relations specialist in the Duke Medical Center