Pediatric transplantation

Analysis of the OPTN/SRTR database demonstrates that, in 2002, pediatric recipients accounted for 7% of all recipients, while pediatric individuals accounted for 14% of deceased organ donors. For children fortunate enough to receive a transplant, there has been continued improvement in outcomes following all forms of transplantation. Current 1-year graft survival is generally excellent, with survival rates following transplantation in many cases equaling or exceeding those of all other recipients. In renal transplantation, despite excellent early graft survival, there is evidence that long-term graft survival for adolescent recipients is well below that of other recipients. A causative role for noncompliance is possible. While the significant improvements in graft and patient survival are laudable, waiting list mortality remains excessive. Pediatric candidates awaiting liver, intestine, and thoracic transplantation face mortality rates generally greater than those of their adult counterparts. This finding is particularly pronounced in patients aged 5 years and younger. While mortality awaiting transplantation is an important consideration in refining organ allocation strategies, it is important to realize that other issues, in addition to mortality, are critical for children. Consideration of the impact of end-stage organ disease on growth and development is often equally important, both while awaiting and after transplantation.     

Pediatric Transplantation in the United States, 1995–2004

This article reviews trends in pediatric solid organ transplantation over the last decade, as reflected in OPTN/SRTR data. In 2004, children younger than 18 years made up nearly 3% of the 86 378 candidates for organ transplantation and nearly 7% of the 27 031 organ transplant recipients. Children accounted for nearly 14% of the 7152 deceased organ donors. The transplant community recognizes important differences between pediatric and adult organ transplant recipients, including different etiologies of organ failure, surgical procedures that are more complex or technically challenging, effects of development on the pharmacokinetic properties of common immunosuppressants, unique immunological aspects of transplant in the developing immune system and increased susceptibility to posttransplant complications, particularly infectious diseases. For these reasons, and because of the impact of end-stage organ failure on growth and development, the transplant community has generally provided pediatric candidates with special consideration in the allocation of deceased donor organs. Outcomes following kidney, liver and heart transplantation in children often rank among the best. This article emphasizes that the prospects for solid organ transplantation in children, especially those aged 1–10 years are excellent. It also identifies themes warranting further consideration, including organ availability, adolescent survival and challenges facing pediatric transplant clinical research.     

Current status of kidney and pancreas transplantation in the United States, 1994–2003

This article reviews the OPTN/SRTR data collected on kidney and pancreas transplantation during 2003 in the context of trends over the past decade. Overall, the transplant community continued to struggle to meet the increasing demand for kidney and pancreas transplantation. The number of new wait-listed kidney registrants under the age of 50 has remained relatively stable since 1994, but the number of new registrants aged 50 to 64 has doubled. However, there was only a 2.3% increase in the total number of kidney transplants performed in 2003. Expanded criteria donor kidneys made up 20% of all recovered kidneys and 16% of all transplants performed, compared with 15% in the prior year. In May 2003, new rules were implemented to promote equity in kidney organ allocation. These changes seem to have improved access for historically disadvantaged groups, though they have reduced the quality of HLA matching. The effects on long-term outcomes have yet to be measured. Although the majority of SPK recipients are white (82%), the percentage of simultaneous kidney-pancreas recipients who are African-American has increased from 9% in 2000 to 16% in 2003. The percentage of Hispanic/Latino recipients increased from 5% to 9% over the same period.     

Liver and intestine transplantation: summary analysis, 1994–2003

With nearly two years of data available since the inception of the MELD and PELD allocation system, this article examines national OPTN/SRTR data to describe trends in waiting list composition, waiting list mortality, transplant rates, and patient and graft outcomes for liver transplantation.
Following a 6% reduction in the size of the waiting list after MELD was implemented in 2002, the number of patients on the waiting list grew by 2% from 2002 to 2003, while the number of liver transplants increased by 6%. The overall death rate while on the liver waiting list has decreased from 225 deaths per 1,000 patient years in 1994 to 124 deaths in 2003. As with the waiting list death rates, post-transplant death rates have also decreased over the past decade. Unadjusted one-year patient survival was lower for older donor age groups (88% for donors aged 18–34, 87% for donors aged 35–49, 85% for donors aged 50-64); a similar trend was observed at three and five years following transplantation.
Intestine transplantation is performed with slowly increasing frequency and success. Early graft losses and rejection rates have changed little since 1994, but rejection is easier to control and long-term survival is improving.     

Thoracic organ transplantation in the United States, 1994–2003

Using OPTN/SRTR data, this article reviews the state of thoracic organ transplantation in 2003 and the previous decade. Time spent on the heart waiting list has increased significantly over the last decade. The percentage of patients awaiting heart transplantation for >2 years increased from 23% in 1994 to 49% by 2003. However, there has been a general decline in heart waiting list death rates over the decade. In 2003, the lung transplant waiting list reached a record high of 3,836 registrants, up slightly from 2002 and more than threefold since 1994. One-year patient survival for those receiving lungs in 2002 was 82%, a statistically significant improvement from 2001 (78%). The number of patients awaiting a heart-lung transplant, declining since 1998, reached 189 in 2003. Adjusted patient survival for heart-lung recipients is consistently worse than the corresponding rate for isolated lung recipients, primarily due to worse outcomes for heart-lung recipients with congenital heart disease. A new lung allocation system, approved in June 2004, derives from the survival benefit of transplantation with consideration of urgency based on waiting list survival, instead of being based solely on waiting time. A goal of the policy is to minimize deaths on the waiting list.     

Thoracic Organ Transplantation in the United States, 1995–2004

This article reviews trends in thoracic organ transplantation based on OPTN/SRTR data from 1995 to 2004. The number of active waiting list patients for heart transplants continues to decline, primarily because there are fewer patients with coronary artery disease listed for transplantation. Waiting times for heart transplantation have decreased, and waiting list deaths also have declined, from 259 per 1000 patient-years at risk in 1995 to 156 in 2004. Fewer heart transplants were performed in 2004 than in 1995, but adjusted patient survival increased to 88% at 1 year and 73% at 5 years. Emphysema, idiopathic pulmonary fibrosis and cystic fibrosis were the most common indications among lung transplant recipients in 2004. Waiting time for lung transplantation decreased between 1999 and 2004. Waiting list mortality decreased to 134 per 1000 patient-years at risk in 2004. One-year survival following transplantation has improved significantly in the past decade. The number of combined heart-lung transplants performed in the United States remains low, with only 39 performed in 2004. Overall unadjusted survival, at 58% at 1 year and 40% at 5 years, is lower among heart-lung recipients than among either heart or lung recipients alone.     

Kidney and Pancreas Transplantation in the United States, 1995–2004

This article examines OPTN/SRTR data on kidney and pancreas transplantation for 2004 and the previous decade, and discusses recent changes in kidney-pancreas (KP) allocation policy and emerging issues in kidney donation after cardiac death (DCD). Although the number of kidney donors continues to increase, new waiting list registrations again outpaced the number of kidney transplants performed, rising by 11% between 2003 and 2004 and contributing to a 1-year increase of 8% in the number of patients active on the waiting list. DCD has increased steadily since 2000; 39% more DCD transplants were performed in 2004 than 2003. Both deceased donor and living donor kidney graft survival rates remain excellent and are improving. The number of people living with a functioning kidney transplant doubled between 1995 and 2004, to 101 440 with a functioning kidney-alone and 7213 with a functioning KP. Health care providers in all settings are more likely to be exposed to these transplant recipients. Patient survival following simultaneous pancreas-kidney (SPK) transplantation is excellent and has improved incrementally since 1995; death rates in the first year fell from 60 per 1000 patient-years at risk in 2001 to 45 in 2003. The number of solitary pancreas transplants increased dramatically in 2004.     

Pediatric Transplantation in the United States, 1996–2005

Solid organ transplantation is accepted as a standard lifesaving therapy for end-stage organ failure in children. This article reviews trends in pediatric transplantation from 1996 to 2005 using OPTN data analyzed by the Scientific Registry of Transplant Recipients. Over this period, children have contributed significantly to the donor pool, and although the number of pediatric donors has fallen from 1062 to 900, this still accounts for 12% of all deceased donors. In 2005, 2% of 89 884 candidates listed for transplantation were less than 18 years old; in 2005, 1955 children, or 7% of 28 105 recipients, received a transplant. Improvement in waiting list mortality is documented for most organs, but pretransplant mortality, especially among the youngest children, remains a concern. Posttransplant survival for both patients and allografts similarly has shown improvement throughout the period; in most cases, survival is as good as or better than that seen in adults. Examination of immunosuppressive practices shows an increasing tendency across organs toward tacrolimus-based regimens. In addition, use of induction immunotherapy in the form of anti-lymphocyte antibody preparations, especially the interleukin-2 receptor antagonists, has increased steadily. Despite documented advances in care and outcomes for children undergoing transplantation, several considerations remain that require attention as we attempt to optimize transplant management.     

Kidney and pancreas transplantation

Data from the Scientific Registry of Transplant Recipients offer a unique and comprehensive view of US trends in kidney and pancreas waiting list characteristics and outcomes, transplant recipient and donor characteristics, and patient and allograft survival. Important findings from our review of developments during 2002 and the decade's transplantation trends appear below.
The kidney waiting list has continued to grow, increasing from 47 830 in 2001 to 50 855 in 2002. This growth has occurred despite the increasing importance of living donor transplantation, which rose from 28% of total kidney transplants in 1993 to 43% in 2002.
Policies and procedures to expedite the allocation of expanded criteria donor (ECD) kidneys were developed and implemented during 2002, when 15% of deceased donor transplants were performed with ECD kidneys. Unadjusted 1- and 5-year deceased donor kidney allograft survivals were 81% and 51% for ECD kidney recipients, and 90% and 68% for non-ECD kidney recipients, respectively.
Although more patients have been placed on the simultaneous kidney-pancreas waiting list, the number of these transplants dropped from a peak of 970 in 1998 to 905 in 2002. This decline may be due to competition for organs from increasing numbers of isolated pancreas and islet transplants.     

Liver and Intestine Transplantation in the United States, 1995–2004

Three years of survival data are now available and the impact of the model for end-stage liver disease (MELD) allocation system is becoming clear. After a decline in new registrants to the waiting list in 2002, the number increased to 10 856 new patients in 2004. Since the implementation of MELD, the percentage of patients who have been on the list for 1–2 years has declined from 24% to 19%. There has been a shift upward in the percentage of patients with higher MELD scores on the waiting list.
An increasing percentage of adult living donor liver recipients are over the age of 50 years; from 1% in 1997 to 51% in 2004. Parents donating to children (93% of living donors in 1995), represented only 14% in 2004. Long-term adjusted patient survival declined with increasing recipient age in adults following either DDLT or LDLT.
Cirrhosis caused by chronic hepatitis C virus (HCV) is the leading indication for liver transplantation and is associated with reduced long-term survival in recipients with HCV compared to those without HCV, 68% at 5 years compared to 76%.
Although the intestine waiting list has more than doubled over the last decade, an increasing number of centers now perform intestinal transplantation with greater success.     

Liver and intestine transplantation

The most significant development in liver transplantation in the USA over the past year was the full implementation of the MELD- and PELD-based allocation policy in March 2002, which shifted emphasis from waiting time within broad medical urgency status to prioritization by risk of waiting list death. The implementation of this system has led to a decrease in pretransplant mortality without increasing post-transplant mortality, despite a higher severity of illness at the time of transplant.
The trend over the last few years of rapidly increasing numbers of adult living donor liver transplants was reversed in 2002 by a decline of more than 30% in the number of these procedures. In 2002, a greater percentage of women received livers from living donors (43%) than deceased donors (34%), possibly because of size considerations.
From 1993 to 2001, the waiting list increased more than sixfold, from 2902 patients to 18 047 patients. For the first time since 1993, the waiting list size decreased in 2002, dropping 6% to 16 974 candidates. The percentage of temporarily inactive liver candidates also increased from 2001, thus the net decrease in the active waiting list for 2002 was 12%. This may reflect a trend toward less pre-emptive listing practices under MELD.
Intestine transplantation remains a low-volume procedure limited to a few transplant centers and is still accompanied by significant pre- and post-transplantation risks. As this procedure matures, its application may increase to include recipients at an earlier stage of their disease with better likelihood of success.     

Thoracic organ transplantation

This article presents an overview of factors associated with thoracic transplantation outcomes over the past decade and provides valuable information regarding the heart, lung, and heart-lung waiting lists and thoracic organ transplant recipients. Waiting list and post-transplant information is used to assess the importance of patient demographics, risk factors, and primary cardiopulmonary disease on outcomes.
The time that the typical listed patient has been waiting for a heart, lung, or heart-lung transplant has markedly increased over the past decade, while the number of transplants performed has declined slightly and survival after transplant has plateaued. Waiting list mortality, however, appears to be declining for each organ and for most diseases and high-severity subgroups, perhaps in response to recent changes in organ allocation algorithms. Based on perceived inequity in organ access and in response to a mandate from Health Resources and Services Administration, the lung transplant community is developing a lung allocation system designed to minimize deaths on the waiting list while maximizing the benefit of transplant by incorporating post-transplant survival and quality of life into the algorithm. Areas where improved data collection could inform evolving organ allocation and candidate selection policies are emphasized.     

Liver and Intestine Transplantation in the United States, 1997–2006

Liver transplantation in 2006 generally resembled previous years, with fewer candidates waiting for deceased donor liver transplants (DDLT), continuing a trend initiated with the implementation of the model for end-stage liver disease (MELD). Candidate age distribution continued to skew toward older ages with fewer children listed in 2006 than in any prior year. Total transplants increased due to more DDLT with slightly fewer living donor liver transplants (LDLT). Waiting list deaths and time to transplant continued to improve. In 2006, there also were fewer DDLT for patients with MELD <15, fewer pediatric Status 1A/B transplants and more transplants from donation after cardiac death (DCD) donors. Adjusted patient and graft survival rates were similar for LDLT and DDLT. This article also contains in-depth analyses of transplantation for hepatocellular carcinoma (HCC). Recipients with HCC had lower adjusted 3-year posttransplant survival than recipients without HCC. HCC recipients who received pretransplant ablative treatments had superior adjusted 3-year posttransplant survival compared to HCC recipients who did not. Intestinal transplantation continued to slowly increase with the largest number of candidates on the waiting list since 1997. Survival rates have increased over time. Small children waiting for intestine grafts continue to have the highest waiting list mortality.