The AJT Report: News and issues that affect organ and tissue transplantation

Abstract

This month, “The AJT Report” takes a look at ways to improve quality of life for pediatric transplant patients, and also reviews China's new organ donation policy.

Our Generation of Chronically Ill Children

While life-saving transplantation is typically the first concern for a family with a critically ill child, the longerterm issues can also be significant. According to Angela Green, PhD, pediatric researcher at Arkansas Children's Hospital in Little Rock, “Parents often acknowledge that they were told about complications prior to transplantation, but at the time were focused on the ‘here and now’ to keep their child alive. The chronic nature of the illness and potential morbidity were in the back of their minds.”

A number of studies have looked at quality-of-life (QOL) issues for transplanted children. Researchers have noted improvements such as mucus-free lungs for cystic fibrosis patients or functioning kidneys for children with end-stage renal disease. However, other studies have pointed to concerns such as delayed physical development, diminished stamina, self-esteem problems related to health and social interactions and fear of skin pricks or biopsies.

Dr. Green, who has conducted extensive QOL research with transplanted children and their parents, says, “Transplantation is palliative rather than curative for most children; we merely exchange one chronic illness for another.” In a study of perceived QOL for children ages 6 to 12, she found that “parents may not fully appreciate the impact of struggles on their children's quality of life.”¹ For example, children noted teasing and bullying. One child says kids poked fun at her scar.

Too often, QOL is under-evaluated. “While we have made a lot of progress in survival and in managing medical morbidity in transplant children, we have paid less attention to psychosocial issues and quality of life,” says Dr. Green. “We have to move past this and help children deal with the myriad issues they face after transplant,” she adds. “The first step in this is systematically assessing QOL in the clinical setting.”

At Stanford Medical Center in Palo Alto, Calif., pediatric nephrologist Minnie Sarwal, MD, PhD, is doing just that. After publishing a paper in Pediatric Transplantation on risk factors for nonadherence in children, she and her colleagues changed their practice to include both a dedicated psychologist and social worker in the transplant clinic to handle psychosocial problems, especially those related to non-adherence.²

Studies Underway

In an effort to take a comprehensive look at pediatric quality of life in kidney, liver and heart recipients, Stacee Lerret and Gail Stendahl, transplant coordinators at Children's Hospital of Wisconsin in Milwaukee, are undertaking a 10-year study with 150 children. “We see patients and families experience many stressors,” says Lerret. “Every day we monitor their drug levels; we look to see how their graft is functioning. But we needed to get a better understanding of how they're dealing with quality-of-life issues.” Lerret and Stendahl hope to identify patterns of adaptation that differ in the heart, kidney and liver, as well as determine changes in recipient QOL over time.

Meanwhile, a number of researchers are also looking at alternatives to heavy immunosuppression for children. “We're creating a population of children who see the consequences of long-term drug use,” says Lori West, MD, PhD, director of Heart Transplantation Research at the University of Alberta in Edmonton. “One way of getting around it is to understand the immature immune system better. Scientifically, we're not taking as much advantage as we could to exploit the naïve juvenile immune system to diminish an immune response.”

Several years ago, Dr. West and her colleagues began studying ABO blood group mismatch transplants. By exploiting the fact that babies don't mount a vigorous immune response to blood groups and therefore don't have the hyperacute rejection that older patients do, her team began infant heart transplants without aggressive immunosuppression in 1996. They reported their work in 2001, and by 2005 there were about 15 to 20 centers in six countries using their protocol, she says.³ Today that number has risen to about 25 centers in 10 countries.

While we have made a lot of progress in survival in transplant children, we have paid less attention to psychosocial issues.—Angela Green, PhD

Dr. West is continuing her studies, looking at the full spectrum of pediatrics. “People sometimes forget that the infant is different from the toddler, who is different from the young child, who is different from the adolescent. It's a moving target. It may be that the infant is the only one with these particular immaturities that can be exploited. On the other hand, there may be certain features of childhood immunity that we just don't understand well enough.”

Meanwhile, at Stanford Medical Center, Dr. Sarwal has joined forces with Allan Kirk, MD, PhD, professor of surgery in the Division of Transplantation at Atlanta's Emory University, and a team at the University of California, Los Angeles Mattel Children's Hospital in a three-year study looking at the role of viruses in heightening a child's immune response to a renal transplant. “We'll look at children aged 1 through 20 [years] to determine their specific response to some very defined viruses (e.g., cytomegalovirus, Epstein-Barr, BK, adenovirus) that we know are important in transplantation,” says Dr. Kirk. “Our hypothesis is that the amount of overlap between immune response to a virus and immune response to an organ will determine how aggressively people will respond and the likelihood of rejection.”

The Emory-Stanford-UCLA study, which will also catalog and define how pediatric kidney transplant patients' T-cell repertoires evolve as they get older, is one of four studies funded by Clinical Trials in Organ Transplantation in Children (CTOTC). Another of these studies seeks to understand how viral infections trigger chronic problems in lung transplant recipients. A third CTOTC study will look at pediatric heart transplantation across a positive donor-specific cross-match, and the fourth study is investigating immunosuppression minimization to single-drug therapy with sirolimus in pediatric transplantation.

Improving Quality of Life

Dr. Sweet adds that developing tools to effectively assess QOL in children, both pre- and post-transplant (as well as in adults), is imperative. “I think that as we evolve our ability to allocate these scarce organs, being able to fold quality of life into that allocation process will be critical,” he says.

China Begins New Donation System

China's Vice Minister of Health, Huang Jiefu, MD, and the English-language newspaper China Daily announced in late August that China has established new national organ donation system to increase consented donors, halt rgan trafficking and quell the long-time dependence on use of organs from executed prisoners.¹ A pilot project for the system, which will be operated mainly by the Red Cross Society of China with assistance from the Ministry of Health, will begin in 10 provinces and cities.

Within the China Daily article Dr. Huang says that prisoners, whom experts estimate account for more than 65% of total donors, “are not a proper source for organ transplants,” nor should transplantation be a privilege for the rich.

Noting that “the candid observation by the Vice Minister is courageous and commendable,” Francis L. Delmonico, MD, director of medical affairs for The Transplantation Society, advisor for human transplantation for the World Health Organization and a Harvard professor of surgery, says the concern of the international community regarding the recovery of organs from executed prisoners is that the need for organs has fueled the need, or demand, for executions. “The expectation that a foreign patient can undergo transplantation in China on a specified date—with blood type compatibility—brings that concern to a reality,” he adds. He also says the international community, as represented by the Istanbul Declaration, supports the intention of China to establish a deceased donation system.

Statement From The Transplantation Society

While we can see some ‘green shoots’ of a new and ethical transplant program focused on meeting the needs of the Chinese community with end-stage organ failure, there is a long way still to go. There is no doubting that the Chinese Government in Beijing is determined to curtail the grisly trade in executed prisoners, so it seems mostly to have gone underground and a new trade in commercial living kidney and liver transplantation appears to be springing up. The Transplantation Society remains in contact with many people throughout China and is committed to helping to encourage these new signs of appropriate use of transplantation therapy, while remaining steadfast in opposition to the sale of organs to rich foreign patients.

—Jeremy Chapman, MD, president, The Transplantation Society

The latest efforts in China follow the 2007 Human Organ Transplantation Act that was designed to ban illegal organ trade, give priority to Chinese citizens, and provide new criteria for facilities and surgeons.² At that time, the Ministry of Health said it also hoped to establish a national agency to oversee procurement, allocation and post-transplant data management.