Adult Organ Transplant Research Articles

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.

The incidence of nonadherence after organ transplant: Ensuring that our efforts at counting really count

The incidence of nonadherence after organ transplant: Ensuring that our efforts at counting really count

Rituximab (Chimeric Anti-CD20 Antibody) for Posttransplant Lymphoproliferative Disorder after Solid Organ Transplantation in Adults: Long-Term Experience from a Single Center

Occurrence of posttransplant lymphoproliferative disorder (PTLD) after transplantation is known. Drastic reduction or withdrawal of immunosuppression with anti-viral therapy for Ebstein-Barr virus (EBV) is the primary treatment for all PTLD. Many PTLD are B cell in origin have CD20 antigen on the cell surface. Rituximab is a chimeric anti CD20 antibody, which has been used to treat PTLD with variable success. This study aims to report long-term experience with rituximab for PTLD from a single center. Seventeen patients (13 male, 4 female, mean age 51.2 years) received rituximab to treat PTLD. Five patients received rituximab with drastic reduction in immunosuppression (primary). Nine patients received rituximab after failure of primary therapy (rescue) and three patients received it after resolution of PTLD (prophylactic). Mean follow-up period was 60 months. Overall 1-, 3-, and 5-year patient survivals were 64.7%, 47.1% and 35.3%, respectively. In the primary group, three patients had complete and one had partial response; however, only two (40%) patients are currently alive. In the rescue group, none of the patients had a complete response, four patients had partial response, and only two (22%) patients are currently alive. In the prophylactic group, two patients died at 28 and 41 months due to recurrence and graft failure, respectively. Sixty percent (3 of 5) of patients who received rituximab as primary therapy had complete resolution, and 44% (4 of 9) of patients who received it as rescue therapy had partial response. Overall 5-year patient survival was a disappointing 35%.

Hypogammaglobulinemia in pediatric liver transplant recipients

Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.

Herpes Simplex Virus (HSV)-1 and -2, and Varicella Zoster Virus (VZV)

Herpes Simplex Virus (HSV)-1 and -2, and Varicella Zoster Virus (VZV)

Community-acquired respiratory viruses

Community-acquired respiratory viruses

SEVERE HYPOGAMMAGLOBULINEMIA AFTER PEDIATRIC LIVER TRANSPLANTATION

P702 Aims: Hypogammoglobulininemia has been reported after solid organ transplantation in adults, however, immunoglobulin replacement (IVIG) is only necessary in a minority of affected patients. We previously reported on a patient with severe B cell dysfunction following combined renal and liver transplantation caused by mycophenolate mofetil therapy. The aim of our present study is to present 3 pediatric patients with severe posttransplant hypogammaglobulinemia following liver transplantation (Ltx) receiving a standard immunosuppression consisting of prednisolone and cyclosporin. Patients and results: Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post Ltx the serum IgG was 1.7 g/l. Patient 2 was transplanted at the age of 12 years for acute liver failure. Four weeks later the IgG dropped to 2.6 g/l. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post Ltx severe hypogammaglobulinemia (IgG <1.48 g/l) was diagnosed during a severe infectious complication. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were even postoperatively in the normal range. There was no extensive loss of protein by ascites. Immunoglobulins were replaced in the three patients monthly without further complications. Conclusions: Severe hypogammaglobulinemia is a rare phenomenon following pediatric liver transplantation and seems to be caused by immunosuppressive drugs. Calcineurininhibitors might have a negative impact on IgG production by an impaired T cell help on B cells. A screening for hypogammaglobulinemia is helpful after pediatric Ltx, and further immunological research is necessary in affected patients.

Posttransplant Diabetes Mellitus: Cause, Impact, and Treatment Options

The incidence of diabetes mellitus (DM) is increased in adult organ transplant recipients. As many as 30% to 45% of solid organ adult transplant patients have DM before transplantation or develop posttransplant diabetes mellitus (PTDM). Risk factors for PTDM include family history, ethnic or genetic background, insulin resistance, and diabetogenic effects of immunosuppressive medications. Posttransplant hyperglycemia may result in increased platelet aggregation, increased wound infections, dehydration, and loss of lean body mass. More significantly, long-term complications of DM such as coronary artery disease and peripheral vascular disease may be exacerbated with the use of immunosuppressive medications whose known side effects include hyperglycemia, hyperlipidemia, and hypertension; these effects may lead to premature transplant graft dysfunction. Treatment goals for PTDM reflect those of the American Diabetes Association guidelines; long-term management is linked with early, patient-centered education and optimizing minimally diabetogenic immunosuppressive medication regimens. A multidisciplinary team including the patient, family/support people, transplant surgeon, transplant physician, transplant nurse coordinator, transplant social worker, pharmacist, dietitian, and diabetes educator is crucial to long-term management of PTDM.

Evidence-based immunosuppression after pediatric renal transplantation—A dream?

IT IS INCREASINGLY evident that only prospective, randomized controlled clinical trials provide the highest level of evidence to compare therapeutic regimens. Clinical trials provide the framework to search for more effective and less toxic immunosuppressive agents to control solid organ transplant rejection. While systematic reviews have been presented on immunosuppression after solid organ transplantation in adults, the pediatric literature on randomized controlled clinical trials remains extremely scarce. Most trials have evaluated the safety and efficacy of recombinant human growth hormone after pediatric renal transplantation. In a relatively small trial after pediatric liver transplantation, two antihypertensive agents were compared in addition to a cyclosporine-based immunosuppressive protocol. Large-scale randomized controlled clinical trials have been few until recently. There was one trial comparing the efficacy and safety of prophylactic treatment with OKT3 monoclonal antibody versus antilymphocyte globulin induction therapy after pediatric renal transplantation. There have been several large-scale, randomized, multicenter trials in adult renal transplant recipients comparing the clinical efficacy and safety of both calcineurin inhibitors, combined with azathioprine and corticosteroids as adjunctive therapies. Acute allograft rejection was significantly reduced with tacrolimus compared with cyclosporine-based immunosuppressive therapy. There is only one similar trial in children. However, there also is a large randomized controlled trial in the United States comparing OKT3 induction therapy with IV cyclosporine. This trial has not yet been published. The aim of this manuscript is to review the existing trials to find explanations for the lack of development but obvious need for such trials in pediatric solid organ transplantation.

The pathogenesis and management of influenza virus infection in organ transplant recipients.

Infection with influenza viruses poses specific problems in adult and pediatric organ transplant recipients, including a higher rate of pulmonary and extra-pulmonary complications. Also, data suggest that influenza is associated with acute cellular rejection and chronic allograft dysfunction. The main strategy of influenza prevention has been influenza immunization in order to stimulate local and systemic antibodies. However, studies have shown that antibody response to inactivated influenza vaccine is decreased in all groups of organ transplant recipients. A live attenuated influenza virus vaccine is nearing approval in the United States. However, studies are needed in organ transplant recipients to determine whether the live attenuated influenza virus vaccine can enable these patients to mount a protective immune response and what degree of protection or amelioration of illness is provided by such vaccine. It is also important to verify the safety of this vaccine in organ transplant recipients because live virus may cause severe disease in these patients. Therefore, other modalities of prevention against influenza, such as chemoprophylaxis with antiviral drugs, should be considered in this patient population. The current review provides an overview of the incidence, clinical manifestations, and strategies for the prevention and management of influenza in organ transplant recipients.

Intrathoracic organ transplantation in adults with congenital heart disease

Background: Advances in the management of congenital heart disease mean that many children now survive to adulthood. They constitute an increasingly important population, many of whom will eventually require an intrathoracic transplant.

The diagnostic value of high resolution ultrasound in non-melanoma skin cancer

The predisposition to skin cancers in childhood is the hallmark of xeroderma pigmentosum (XP), a rare autosomal recessive disorder, deficient in DNA repair and hypersensitive to ultraviolet irradiation. Human papillomavirus (HPVs), are common infections of the skin which are often found associated to benign lesions and non-melanoma skin cancers (NMSC), mainly squamous cell carcinomas (SCC) and basal cell carcinomas (BCC). Our study is the first to analyse 40 SCCs, 27 BCCs and nine normal skin biopsies from XP patients for HPV DNA which are found more frequently in SCCs (20/40) than in BCCs (4/27) or normal skin (2/9). The HPV spectrum includes 22 different epidermodysplasia verruciformis (EV) HPV types, which predominate in SCCs (48%) compared to BCCs (15%) and normal skin (22%). Our data, showing an association between EV HPV and SCCs from young XP patients is comparable to that found for NMSC from adult immunosuppressed organ transplant patients and raises the question of the importance of HPV infection in skin carcinogenesis.

Recovery after Organ Transplantation in Adults

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Hypertension after renal transplantation.

Hypertension is a frequent complication after organ transplantation in both children and adults and is a significant risk factor for the development of cardiovascular disease and graft dysfunction. There are multiple mechanisms responsible for the development of posttransplant hypertension. In the precyclosporine era, chronic rejection was the most common cause. The introduction of cyclosporine A has increased the prevalence of hypertension in solid organ transplant recipients. Cyclosporine increases renal vascular resistance by causing vasoconstriction of the afferent arteriole. From a pathophysiologic point of view, a calcium channel blocker should be used as the initial therapy in patients with cyclosporine-associated hypertension. Hypertension needs to be treated aggressively in all transplant recipients in an attempt to minimize allograft and cardiovascular damage.