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The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post‐transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti‐CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision‐making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted. [ABSTRACT FROM AUTHOR]

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post‐transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein‐Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre‐emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre‐emptive interventions in patients who are EBV seronegative pre‐transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre‐transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre‐emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority. [ABSTRACT FROM AUTHOR]

The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post‐transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre‐emptive strategies. While the group made a strong recommendation for pre‐emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre‐emptive strategy, largely due to insufficient or conflicting evidence. Current gaps and future research priorities are highlighted. [ABSTRACT FROM AUTHOR]

The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosuppressive therapy. If one could safely and effectively exploit neonatal tolerance for successful xenotransplantation of the heart, the challenge of severe cardiac failure in the newborn infant might be met. We discuss the need, the potential for applying neonatal tolerance in the setting of xenotransplantation and the possibility that other approaches to this problem might emerge. [ABSTRACT FROM AUTHOR]

To evaluate social development of pediatric heart transplant (tx) recipients who have lived 15 or more years after transplantation. Among 498 pediatric patients, age less than 18 years, who underwent heart transplantation, at a single institution, 337 were performed between 1985 and 1998. We identified all who survived more than 15 years and engaged them in a survey regarding employment, education, marital, and social status. One hundred and eighty-three recipients (54.3%; 183/337) have survived greater than 15 years; of these, 150 (81.9%) subjects are alive with age ranging from 15.04 from 28 years (median, 23.6 years). Forty-two patients (23%) are independent, 127 (69%) were living at home, and 14 (8%) have been lost to follow-up. Ninety-nine survivors (66%) responded to the survey study. Currently, five recipients are married. Seventy-four completed high school, 21 are enrolled in high school, and four did not complete high school. Of the 47 recipients who started college, 27 are currently enrolled, 11 graduated, and nine did not finish college. Ninety-four patients have health insurance, 40 are employed, and 31 receive financial assistance for a disability. The majority of recipients of pediatric heart transplantation are able to reach reasonable academic milestones, achieve social well-being, and professional independence. [ABSTRACT FROM AUTHOR]

Pediatric heart transplant patients at our institution are immunosuppressed with a CNI and another immune-modulating agent without utilizing corticosteroids. Patients whose renal function worsened and who did not respond to CNI minimization had their CNI discontinued. The clinical history of 35 pediatric heart transplant patients with significant renal insufficiency whose CNI was discontinued was retrospectively analyzed. Data including serum creatinine and weight were collected before, at time of, and every 3-6 months after CNI discontinuation. This was used to calculate an eGFR. Cardiac allograft rejection and mortality data were also collected. CNI discontinuation occurred 39 times in 35 patients. The median eGFR significantly increased by 14 mL/min 3 months after CNI discontinuation and the increase continued to be significant ( P≤.05) at 5 years. Freedom from rejection analysis showed no difference between graft rejection 2 years before versus after CNI discontinuation ( P=.437). No mortality was associated with CNI discontinuation. Immunosuppression free of CNIs and corticosteroids appears to be a safe alternative in pediatric heart transplant patients with significant renal insufficiency. Furthermore, this strategy can significantly reverse renal insufficiency, even late after transplantation. [ABSTRACT FROM AUTHOR]

Chinnock TJ, Shankel T, Deming D, Cutler D, Sahney S, Fitts J, Chinnock RE. Calcineurin inhibitor minimization using sirolimus leads to improved renal function in pediatric heart transplant recipients. Pediatr Transplantation 2011: 15: 746-749. © 2011 John Wiley & Sons A/S. Abstract: The introduction of cyclosporine revolutionized the practice of immunosuppression for solid organ transplant recipients, and has resulted in a significant increase in survival. While CNI use has been the mainstay of immunosuppressive therapy in pediatric heart transplantation, CNIs have been associated with an increased risk of nephropathy leading to significant morbidity and mortality. We evaluated the effect on renal function of a CNI minimization protocol using SRL in pediatric heart transplant patients with CNI induced renal insufficiency. An IRB approved retrospective chart review and case control study was performed. There were 20 patients identified with renal insufficiency who had been converted to SRL (target 5-8 ng/mL) and cyclosporine (target 50-75 vs. 125-150 ng/mL). Renal insufficiency was defined as isotopic (Indium 111 DTPA) GFR <60 mL/min per 1.73 m2 or sCr >1 mg/dL. Outcome variables evaluated were GFR and sCr at time of conversion and at two yr post conversion. Comparison was made with case control subjects matched for age at Tx, time from Tx to conversion, and initial GFR. The median age at Tx = 81 days (S.D. ±26), median time of conversion after Tx = 10 yrs (s.d. ±0.65). Self-limited/treatable side effects included hypercholesterolemia (10), neutropenia (6), aphthous ulcer (3), edema (2), anemia (2), and tremor (1). One patient rejected in the two yr prior to conversion, and one patient had two rejection episodes following conversion. GFR at conversion for study group was 51 ± 14 vs. 60 ± 22 at two yr, p = 0.018. GFR at inclusion for control group was 56 ± 20 vs. 53 ± 21, p = 0.253. This report demonstrates that minimizing CNI exposure by addition of SRL to the immunosuppressant regimen in pediatric heart transplant recipients result in improved renal function in comparison to historically managed patients. Furthermore, immunotherapy with SRL and lower-dose CNI can effectively prevent rejection with an acceptable side-effect profile. [ABSTRACT FROM AUTHOR]

Vascularization of transplanted islets must be maintained to provide long-term graft function. In vivo assessment of new vessel formation in islet grafts has been poorly documented. The purpose of this study was to investigate whether neovascularization was detectable in vivo in a Feridex-labeled murine syngeneic subcapsular islet mass using DCE MRI over 180 days. Subcapsular transplants could be visualized at post-transplant days three, seven, 14, and 28 using T2-weighted MRI and at post-transplant day 180 by immunohistochemistry. Injection of the contrast agent gadolinium (Gd)-DTPA for DCE at three, seven, and 14 days showed increased signal in the transplant area consistent with new vessel formation. Areas under contrast enhancement curves suggested peak angiogenesis at 14 days. At 180 days, there was no observable change in signal intensity after contrast injection suggesting established vascularization or islet mass reduction. Immunohistochemistry confirmed MRI and DCE findings. These data suggest that islet angiogenesis occurs early after transplantation and is likely established after one month of transplantation. This study provides an in vivo time-line of neovascularization in subcapsular islet grafts. We anticipate that contrast extravasation captured by MRI may provide useful monitoring of graft angiogenesis if reproduced in a clinically relevant intraportal model. [ABSTRACT FROM AUTHOR]

To determine the characteristics of pediatric liver transplant recipients who develop GI and/or PTDM, data on children undergoing their first liver transplant from the SPLIT database were analyzed (n = 1611). Recipient and donor characteristics that were evaluated included age at transplant, gender, race, primary disease, hospitalization status at transplant, BMI, recipient and donor CMV status, donor type, donor age, and primary immunosuppression. GI/PTDM was found in 214 individuals (13%) of whom 166 (78%) were diagnosed within 30 days of transplantation (early GI/PTDM). Multivariate analyses suggests that age >5 yr at transplant, hospitalization at transplant, a primary diagnosis other than BA, early steroid use, and tacrolimus use are associated with increased incidence of early GI. Routine monitoring for the development of GI and post-transplant diabetes is indicated in the short- and long-term care of children after liver transplantation. [ABSTRACT FROM AUTHOR]

Most infants and children referred for cardiac transplantation have low cardiac output with concurrent renal hypoperfusion leading to renal insufficiency and failure. This article is a review of the literature of and a single center's experience with combined heart and kidney failure in infants and children less than 10 yr of age. While 39 infants less than 10 yr of age were dialyzed pre- or peri-operatively, none required dialysis support at the time of discharge or in 5–10 yr follow-up. Based on our experience we recommend heart transplant alone in infants and young children with primary heart disease even though they have renal dysfunction. [ABSTRACT FROM AUTHOR]

We report long-term follow up data on cadaveric renal transplantation for end stage renal failure (ESRF) in spina bifida children. Between February 1989 and July 2001, 12 cadaveric renal transplants were performed in 10 children, eight females and two males. Mean age at transplantation was 13.4 yr (range 9–16). Of the patients, eight were wheelchair bound and two were independently mobile. Before transplantation surgical management of the urological tract included, enterocystoplasty and clean intermittent-self catheterization in five patients and ileal conduit urinary diversion in one. A total of eight patients were on renal replacement therapy before receiving the graft while two underwent pre-emptive transplantation. The 1- and 5-yr graft survival rates were 81 and 81%, respectively. Four grafts failed - two patients have successfully undergone subsequent transplantation. Causes of graft failure were chronic rejection in two, acute rejection and vascular thrombosis in one and vascular thrombosis in one patient, respectively. Two patients died after graft nephrectomy. At a median follow-up of 4.08 yr (range 1 day to 10.65 yr), eight of the 12 grafts are functioning with median serum creatinine of 123 mmol/L (range 65– 169). These data demonstrate the feasibility of cadaveric renal transplantation in patients with spina bifida and ESRF. We currently recommend that patients with spina bifida should not be deprived of the benefits of renal transplantation. [ABSTRACT FROM AUTHOR]

This review details the indications for heart transplantation in children. Contraindications have evolved from absolute to relative. Controversial issues remain and this paper represents a consensus of more than a dozen centers that have programs that remain active performing pediatric heart transplants. [ABSTRACT FROM AUTHOR]

This study was undertaken to assess the incidence, indications, and predisposing factors for pacemaker placement in a pediatric heart transplant population. From November 1985 to May 1994, 246 pediatric patients have undergone cardiac transplantation at Loma Linda University Medical Center. Seven (2.8%) have received pacemaker placement with an 8-50 month follow-up period. Median age at transplant was 462 days (0 days to 2.5 years). The median time to pacemaker placement was 190 days (18-1,672 days) after transplantation. Indications were sick sinus syndrome (SSS) in 5 and heart block in 2 patients (1 during acute rejection). Three patients with SSS underwent electrophysiology studies (EPS); 1 was normal and 2 showed sinus node dysfunction. The mode of pacing was WIR in 6 patients and WI in 1 patient. All 6 survivors are doing well and 5 patients' pacemakers still provide support. These 7 patients were compared with 185 pediatric patients (0 days to 12-years-old) transplanted during 1985 through 1993 who survived at least 6 months after transplantation. There was no correlation between the receipt of a pacemaker and graft cold ischemic time, rejection history, donor age, or recipient age at transplantation. The 5 patients with SSS had significantly lower average heart rates in the first month after transplantation (108 ± 16 vs 130 ± 12; P = 0.0002). The need for permanent pacemakers in this population is uncommon. Pacemakers, however, can be safely performed when necessary with excellent clinical results. [ABSTRACT FROM AUTHOR]

Editorial. Comments on the ethical and moral issues which practitioners and the pediatric community must address about the transplantation of organ in infants and infants who became organ donors. Discussion on the beginning and ending of life; Human organs that are commonly needed in infant transplantation.

The authors reflect on the paper of T. L'Ecuyer and colleagues on accepting prolonged cardiopulmonary resuscitation (CPR) donors in pediatric heart transplant recipients. They mention that the authors explores the question on the existence of difference in recipient survival where donors received CPR greater than 30 minutes. They state that L'Ecuyer and colleagues show that the perceived risks in accepting prolonged CRP donors may not be as risky as it seems.