Solid Organ Transplantation In Children Research Articles

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: IV-consensus guidelines for the management of post-transplant lymphoproliferative disorders in children and adolescents.

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.

The IPTA Nashville Consensus Conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: III - Consensus guidelines for Epstein-Barr virus load and other biomarker monitoring.

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.

Prevention and management of CMV infection in pediatric solid organ transplant recipients.

Human cytomegalovirus (CMV) remains one of the most common opportunistic infections following solid organ transplantation in children. CMV causes morbidity and mortality through direct tissue-invasive disease and indirect immunomodulatory effects. In recent years, several new agents have emerged for the prevention and treatment of CMV disease in solid organ transplant recipients. However, pediatric data remain scarce, and many of the treatments are extrapolated from the adult literature. Controversies exist about the type and duration of prophylactic therapies and the optimal dosing of antiviral agents. This review provides an up-to-date overview of treatment modalities used to prevent and treat CMV disease in solid organ transplant (SOT) recipients.

The IPTA Nashville consensus conference on Post-Transplant lymphoproliferative disorders after solid organ transplantation in children: II-consensus guidelines for prevention.

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.

The IPTA Nashville consensus conference on post-transplant lymphoproliferative disorders after solid organ transplantation in children: I-Methodology for the development of consensus practice guidelines.

The International Pediatric Transplant Association (IPTA) Consensus Conference on Practice Guidelines for the Diagnosis, Prevention, and Management of Post-Transplant Lymphoproliferative Disorders after Solid Organ Transplantation in Children took place on March 12-13, 2019, and the work of conference members continued until the end of December 2021. The goal was to produce evidence-based consensus guidelines on the definitions, diagnosis, prevention, and management of PTLD and related disorders based on the critical review of the literature and consensus of experts. This report describes the goals, organization, and methodology of the consensus conference and follow-up activities. The results of each working group (Definitions, Prevention, Management, and Epstein-Barr viral [EBV] load/Biomarker Monitoring) are presented in separate manuscripts within this volume of Pediatric Transplantation.

Long-term respiratory outcomes following solid organ transplantation in children: A retrospective cohort study.

Solid-organ transplantation (SOT) has become commonly used in children and is associated with excellent survival rates into adulthood. Data regarding long-term respiratory outcomes following pediatric transplantation are lacking. We aimed to describe the prevalence and nature of respiratory pathology following pediatric heart, kidney, and liver transplant, and identify potential risk factors for respiratory complications. Retrospective review involving all children under active follow-up at the provincial transplant service in British Columbia, Canada, following SOT. Of 118 children, 33% experienced respiratory complications, increasing to 54% in heart transplant recipients. Chronic or recurrent cough with persistent chest x-ray changes was the most common clinical picture, and most infections were with nonopportunistic organisms typically found in otherwise healthy children. A history of respiratory illness before transplant was significantly associated with risk of posttransplant respiratory complications. Eight percentage8% were diagnosed with bronchiectasis, which was more common in recipients of heart and kidney transplant. Bronchiectasis was associated with recurrent hospital admissions with lower respiratory tract infections, treatment of acute rejection episodes, and treatment with sirolimus. Respiratory morbidity is common after pediatric SOT, and bronchiectasis rates were disproportionately high in this patient group. We hypothesize that this relates to recurrent infections resulting from iatrogenic immunosuppression. Direct pulmonary toxicity from immunosuppression drugs may also be contributory. A high index of suspicion for respiratory complications is needed following childhood SOT, particularly in those with a history of respiratory disease before transplant, experiencing recurrent or severe respiratory tract infections, or exposed to intensified immunosuppression.

Promoting bone health in children and adolescents following solid organ transplantation

Solid organ transplantation in children and adolescents provides many benefits through improving critical organ function, including better growth, development, cardiovascular status, and quality of life. Unfortunately, bone status may be adversely affected even when overall status is improving, due to issues with pre-existing bone disease as well as medications and nutritional challenges inherent post-transplantation. For all children and adolescents, bone status entering adulthood is a critical determinant of bone health through adulthood. The overall health and bone status of transplant recipients benefits from attention to regular physical activity, good nutrition, adequate calcium, phosphorous, magnesium and vitamin D intake and avoidance/minimization of soda, extra sodium, and obesity. Many immunosuppressive agents, especially glucocorticoids, can adversely affect bone function and development. Minimizing exposure to "bone-toxic" medications is an important part of promoting bone health in children post-transplantation. Existing guidelines detail how regular monitoring of bone status and biochemical markers can help detect bone abnormalities early and facilitate valuable bone-directed interventions. Attention to calcium and vitamin D supplementation, as well as tapering and withdrawing glucocorticoids as early as possible after transplant, can provide best bone outcomes for these children. Dual-energy X-ray absorptiometry can be useful to detect abnormal bone mass and fracture risk in this population and newer bone assessment methods are being evaluated in children at risk for poor bone outcomes. Newer bone therapies being explored in adults with transplants, particularly bisphosphonates and the RANKL inhibitor denosumab, may offer promise for children with low bone mass post-transplantation.

Diarrhea in the pediatric solid organ transplantation recipient: A multidisciplinary approach to diagnosis and management.

Diarrhea in the pediatric solid organ transplantation (SOT) recipient is a frequent complaint that is associated with significant morbidity and impaired quality of life. There are limited published data regarding the specific epidemiology, diagnostic evaluation, and treatment of diarrhea after SOT in children. Pediatric SOT recipients have an increased risk of developing diarrhea because of a generalized immunosuppressed state, epidemiologic exposures, and polypharmacy. There is a need to standardize the diagnostic evaluation of diarrhea in children after SOT to facilitate an accurate diagnosis and timely treatment. Herein, we review the available published data and propose a systematic, stepwise approach to the evaluation of diarrhea in this high-risk population, focusing on timely diagnosis of both infectious and non-infectious causes, in order to provide focused management. Prospective studies are needed to better assess the true prevalence, risk factors for, etiologies, and complications of diarrhea in pediatric SOT patients that will guide optimal management. Development of effective vaccines and antiviral therapies for enteric viruses may also contribute to improved outcomes.

Risk factors for Clostridioides (Clostridium) difficile infection following solid organ transplantation in children.

Clostridioides (Clostridium) difficile infection (CDI) in pediatric solid organ transplant (SOT) recipients is a growing problem, though CDI risk factors in this population are poorly understood. Our objective was to characterize CDI risk factors in pediatric SOT recipients. This retrospective case-control study, performed at a single freestanding academic children's hospital, included all SOT recipients age 1-22years who were tested for C.difficile by toxin B gene PCR between August 2009 and August 2017. CDI risk factors were assessed by comparing PCR-positive and PCR-negative cases by generalized linear mixed models. Between August 2009 and August 2017, 409 SOTs were performed of which 138 (33.7%), 134 (32.8%), 131 (32.0%), and 6 (1.5%) were kidney, liver, heart, and small intestine transplants, respectively. Of 205 SOT recipients were tested for CDI, with 723 C.difficile PCR tests performed among these patients. 68/205 (33%) patients developed CDI at least once during the study period. Median (interquartile range) time to diagnosis of first CDI following SOT was 8.9 (1.2, 19.6) months. CDI was independently associated with calcineurin inhibitor use at time of C.difficile testing (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.08, 5.24, P=0.03) and systemic antibiotic exposure within 30days of C.difficile testing (OR 1.74, 95% CI 1.08, 2.79, P=0.02). CDI is a common, relatively late post-transplant complication and independently associated with calcineurin inhibitor and systemic antibiotic exposure. The potential impact of specific immunosuppressive drug and antibiotic selection on CDI risk reduction requires further investigation.

Vascularized composite allotransplantation in children: what we can learn from solid organ transplantation.

This review will focus on the lessons learned over several decades of solid organ transplantation in children, and their relevance to the emerging field of pediatric VCA. Particular attention will be focused on the risk-benefit ratio of immunosuppression as it applies to children receiving a life-enhancing transplant as compared with a life-saving transplant. Potential indications for pediatric VCA will be considered. The report in 2015 of the first child to receive a VCA, bilateral upper extremity grafts from a nonrelated deceased donor, is a seminal event. The case is unique in that the child was already immunosuppressed after a prior kidney transplant. Early graft function is excellent and cortical re-organization has been described. Although the risks of immunosuppression remain a formidable obstacle to the wider spread application of VCA for children, careful consideration of indications and outcomes for these innovative procedures, which have the potential to restore form and function not otherwise achievable, is warranted.

Poorer Long-Term Survival Associated with Monomorphic Post-Transplant Lymphoproliferative Disorder After Solid Organ Transplantation in Children

Poorer Long-Term Survival Associated with Monomorphic Post-Transplant Lymphoproliferative Disorder After Solid Organ Transplantation in Children

Cytotoxic T-lymphocyte therapy for post-transplant lymphoproliferative disorder after solid organ transplantation in children.

EBV-CTL immunotherapy targets EBV antigens expressed by tumor cells in PTLD. Data on outcome of EBV-CTL in pSOT patients are limited. The aim of the study is to describe our experience with allogeneic, third-party EBV-CTL for the treatment of PTLD in pSOT patients in a single tertiary center. Retrospective review was performed of all pSOT patients who received EBV-CTL for PTLD. PTLD was diagnosed using World Health Organization histologic criteria. EBV-CTLs were derived from human leukocyte antigen-typed, EBV-seropositive third-party donors, and cryopreserved and maintained by an accredited national blood transfusion service. Ten patients received EBV-CTL for histologically proven PTLD from 1999 to 2016 following liver (n=5), combined intestinal/liver (n=4), and liver/kidney (n=1) transplantation. PTLD occurred at median age of 40months (range: 12-144) and median post-transplant interval of 8months (range: 2-107). Seven had monomorphic, two had polymorphic, and one had Hodgkin-type PTLD. All were of B-cell origin and EBV-positive on histology. EBV-CTL achieved an overall remission rate of 80% (8 of 10). Transient adverse effects included fever, tachycardia, and vomiting. None developed graft-versus-host disease or opportunistic infections. EBV-CTL is an effective treatment for PTLD in pSOT patients, with good remission rate and minimal toxicity.

Immunohistopathology of the Newly Discovered Giant Papillae Tongue Disorder in Organ-Transplanted Children.

Giant papillae tongue disorder (GPTD) is a newly discovered, long-lasting clinical disorder that may develop in organ-transplanted pediatric recipients. The key feature of this disorder is the unique tongue lesion, which comprises swollen fungiform papillae. The aim of this study was to characterize the immunohistopathology of this novel inflammatory condition. Six organ transplanted children with GPTD were included in the study. Routine histopathology and immunohistochemical stainings for CD3, CD4, CD8, CD25, FOXP3, CD20, CD138, CD68, CD1a, CD15, CD23, and mast cell tryptase were performed. Immunohistochemical analyses of the oral lesions revealed a subepithelial infiltrate that was primarily composed of CD3- and CD4-positive T cells, CD20-expressing B cells, macrophages, and CD138-positive plasma cells. The CD20-positive cells did not display the typical B cell morphology, having in general a more dendritic cell-like appearance. The CD138-expressing plasma cells were distinctly localized as a dense infiltrate beneath the accumulation of T cells and B cells. Increased numbers of CD1a-expressing Langerhans cells were detected both in the epithelium and connective tissue. Because no granulomas were observed and only single lesional eosinophils were detected, GPTD does not resemble a granulomatous or eosinophilic condition. We describe for the first time the immunopathological characteristics of a novel inflammatory disorder of the oral cavity, which may develop after solid organ transplantation in children.

Risk-adapted Treatment for Severe B-Lineage Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation in Children.

Optimal management of posttransplant lymphoproliferative disease (PTLD) remains to be defined due to heterogeneity of this condition and lack of predictors of the outcome. Here we report our experience with pediatric PTLD nonresponsive to immunosuppression (IS) withdrawal, managed after stratification into high and low risk according to the presenting features. This is a single-center retrospective review of prospectively enrolled patients. From 2001 to 2011, 17 children were diagnosed with severe B-lineage, CD20+, PTLD after a median of 37 months (range, 5-93) from liver (12), heart (4), or multiorgan (1) transplantation. Treatment was tailored on 2 risk groups: (1) standard-risk (SR) patients received IS reduction and rituximab; (2) high-risk (HR) patients received IS discontinuation, rituximab and polychemotherapy. The cumulative incidence of rejection at 1 and 5 years after the diagnosis of PTLD was 35% (95% confidence interval [95% CI], 18-69%) and 53% (33-85%), respectively, whereas the disease-free survival at 1 and 5 years was 94% (95% CI, 65-99%) and 75% (45-90%), respectively. Three children died, PTLD-free, from different transplant-related complications: primary nonfunction after retransplantation (liver), cytomegalovirus disease 21 months after PTLD treatment (liver), graft dysfunction 25 months after PTLD (heart). Severe B-lineage PTLD after solid organ transplantation may be classified as SR or HR and treated accordingly with a tailored protocol obtaining a satisfactory long-term outcome. This approach accomplishes the control of lymphoproliferation in severe forms as well as the minimization of toxicity in milder PTLDs.

Organ Transplant Tolerance for Children; in Sight for Some

Advances in tolerance protocols in adult organ transplantation have led to a number of patients coming off immunosuppression following transplantation. This success in transplant tolerance has been achieved using both mixed and full chimerism approaches at a number of centers in the US. Internationally, there are also ongoing studies in kidney transplantation using tolerogenic cell therapy that also aim to reduce or remove immunosuppression. This has suggested that “a kidney for life” is possible. Pediatric patients would be the main beneficiaries of such an outcome. Further, in liver transplantation, highly selected patients have been identified who have been able to come off immunosuppression. We describe the current successes of these tolerance protocols and adiscussion of the burden that such protocols would have for children, including an outline of selected pediatric groups where the barriers for enrollment in such protocols would be less and may be justified. In particular, patients with renal failure who may need a bone marrow transplant, patients with renal failure where a bone marrow transplant may benefit systemic disease, or a condition where the treatment of malignancy or bone marrow failure has already caused renal failure. Solid organ transplantation in children is limited by longterm graft failure and the side-effects of immunosuppression, including cardiovascular disease and cancer. Kidney transplants are the most common solid organ transplant in chil

Hodgkin’s Disease / Hodgkin-PTLD after Solid Organ Transplantation in Children: A Report on 16 Patients Treated According to Subsequent Gpoh-HD Treatment Schedules

Post-transplant lymphoproliferative diseases (PTLD) are severe complications of immunosuppressive therapy after solid organ transplantation (SOT) in children. Among those, Hodgkin’s disease (HD) or Hodgkin(-like) PTLD is a rare entity, and systematic data on pathogenesis, treatment, and prognosis are lacking. Here, we report on 16 children and adolescents who were treated according to standard treatment guidelines from the German HD (GPOH-HD) study cente.All patients with HD after SOT reported to the German pediatric PTLD (Ped-PTLD) registry between 1999 and 2013 were included in this analysis (14 of 182 patients = 7.7% of pediatric PTLDs). Data were supplemented by information recorded in the GPOH-HD registry. In addition, 2 U.S. patients treated according to the respective GPOH-HD guidelines were included. Central pathology review was performed in 12/16 cases. Epstein-Barr virus (EBV) in tumor tissue was evaluated by EBER in situ hybridization, immunohistochemistry for LMP-1 or EBNA-2, and/or EBV-PCR. All patients were treated with chemotherapy according to the respective GPOH-HD recommendations (treatment group (TG)-1: 2xOEPA; TG-2: 2xOEPA+2xCOPP/COPDAC; TG-3: 2xOEPA+4xCOPP/COPDAC) tailored according to stage and LDH. Indication for involved field radiotherapy was based on the current study recommendations. Six patients had additional rituximab treatment, two as upfront monotherapy and four as addition to chemotherapy. Events recorded included disease progression, relapse, second malignancy, and death of any cause. Overall and event-free survival was calculated using log-rank test.16 predominantly male (13/16) patients developed HD after SOT, among them 7 renal, 4 liver, and 5 heart transplant recipients. Median age at diagnosis of HD was 13.9 [range 4.3 – 19.4] years with a median duration from SOT to HD of 7.4 [0.75 – 14.3] years. Histopathology review was classified as classical Hodgkin’s disease in 10 patients (nodular sclerosis =1, mixed type =5, epitheloid-cell predominant =2, not further specified =2) and Hodgkin-PTLD in 6 patients. 8 of 10 patients with data evaluable had a negative EBV-serology at transplantation, while antibodies against EBV were detected in 15/15 patients at the time of HD diagnosis. Fifteen of sixteen tumors proved positive for EBV and/or EBV-gene products. As expected, all tumors expressed CD30 and 7 of 16 tumors demonstrated moderate to strong expression of CD20.Staging revealed 1 patient with stage I disease, 8 with stage II, 5 with stage III, and 2 patients with stage IV disease. Four patients presented with extranodal involvement, among them one with graft organ involvement, and three patients with involvement of the gastrointestinal tract. None of the patients had CNS disease. Patients were treated in TG-1 (6 patients), TG-2 (5 patients), TG-3 (4 patients), respectively. One patient received an individualized treatment scheme, and 2 of 16 patients (both TG-2) were assigned to consolidating involved field radiotherapy. Median follow up was 4.1 [0.3 – 9.2] years. One patient in TG-3 died of infection during COPDAC treatment; all others are alive at the time of abstract preparation. Overall survival (OS) at 2 and 5 years was 93%. In addition to the treatment-related death two patients experienced events, 1 relapse after 9 months and 1 secondary malignancy (polymorphic PTLD) after 1.2 years. Event-free survival after HD chemotherapy at 2 and 5 years was 79%. Rituximab monotherapy did not result in long-term remission, both patients relapsed after 0.4 and 2.7 years, respectively. None of the parameters examined (organ graft, stage, treatment group) was significantly associated with overall or event-free survival.In conclusion, HD is a rare type of PTLD in children arising late after SOT, which may lead to underrepresentation in the pediatric patient population. The analysis of 16 patients treated according to a uniform concept represents the largest series reported to date. Almost all cases were EBV-associated. Although tumors often express CD20 rituximab monotherapy does not seem to establish long-lasting remissions. In contrast, the chemotherapy regimens based on the German protocols for de novo Hodgkin’s disease present well tolerated and effective treatment strategies for HD after SOT in children. International efforts are warranted to improve understanding and treatment for this rare disease. DisclosuresNo relevant conflicts of interest to declare.

Response-Adapted Sequential Immuno-Chemotherapy of Post-Transplant Lymphoproliferative Disorders in Pediatric Solid Organ Transplant Recipients: Results from the Prospective Ped-PTLD 2005 Trial

Post-transplant lymphoproliferative diseases (PTLD) are severe complications of immunosuppressive treatment after solid organ transplantation (SOT). Most pediatric cases are associated with Epstein-Barr virus (EBV). Despite morphologic features similar to de novo lymphomas PTLDs are sensitive to immune interventions alone. We conducted a non-randomized prospective multicenter study to test a response-adapted sequential treatment with rituximab +/- chemotherapy in pediatric patients with CD20+ PTLD (Ped-PTLD Pilot 2005).Pediatric patients (<18 years) with biopsy proven CD20+ PTLD without CND involvement were treated with 3 weekly infusions of rituximab 375 mg/m2. If at least a partial response was obtained in week 3 patients received 3 further rituximab administrations every 3 weeks. In case of stable disease or progression patients were stratified to receive a moderate chemotherapy regimen (mCOMP: day 1 vincristine, prednisone, cyclophosphamide, and day 15 methotrexate; repeat every 4 weeks for 6 cycles). Overall (OS) and event-free (EFS) survival at 2 years were the primary endpoints of the trial. Epstein-Barr virus (EBV) in tumor tissue was evaluated by EBER in situ hybridization, immunohistochemistry for LMP-1 or EBNA-2, and/or EBV-PCR.49 patients (mean age 9.8 [0.8-17.4] years) were included, among them 18 renal, 11 liver graft recipients, and 20 patients after heart or lung transplantation. Median time from SOT to PTLD was 4.7 [0.15 – 15] years (17 early, 32 late PTLDs). Tumor cells contained EBV products in 44 of 49 cases. Histology was polymorphic in 12 patients, diffuse large B cell lymphoma (DLBCL) in 24, Burkitt lymphoma in 7, and other high grade B cell lymphomas in 6 patients upon central review. Median follow-up is 4.5 years. 32 patients (64%) received rituximab only, of which 26 (81% of responders, 53% of total study population) remain alive and in continuous complete remission with a median follow up of 4.9 years. The remaining 6 rituximab responders experienced relapse (n=4), secondary malignancy (n=1), or death unrelated to PTLD (n=1). 15 patients had stable or progressive disease after initial rituximab treatment and proceeded to chemotherapy. Of these, 10 patients (66%) converted to complete remission while 4 patients (27%) progressed and went off study to receive intensive chemotherapy. 1 patient died during mCOMP treatment, which could not be distinguished between tumor progression and infection. 2/49 patients died of PTLD before rituximab response could be evaluated. 2-year OS was 86% +/- 5% with 67% +/- 7% surviving event-free. Estimated 5-year OS and EFS were 83% +/-5% and 67% +/-7%, respectively. 6/7 patients with Burkitt histology required mCOMP chemotherapy. Patients after thoracic organ transplantation had a significantly inferior outcome compared to liver or renal graft recipients (5-years EFS 79%+/-8% vs 44% +/-11%, p=0.01). There was no significant impact of tumor EBV-status, histology, stage or early/late PTLD development. Treatment-related mortality was attributed to bowel perforation (n=1) and infection (n=2). No episode of graft rejection occurred during treatment for PTLD.In conclusion, response-adapted immuno-chemotherapy is an effective and well tolerated treatment regimen for CD20-positive PTLD after SOT in children. Chemotherapy could be spared in half of the PTLD patients, but was necessary in almost all Burkitt PTLD patients. Prognosis was significantly worse in patients after heart or lung transplantation compared to renal or liver allograft recipients. Future studies are envisioned to evaluate whether the inclusion of cellular immunotherapy may contribute to avoid chemotherapy in the majority of patients. DisclosuresNo relevant conflicts of interest to declare.

Pediatric vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) has experienced a growing acceptance, which has led to a debate centered on extending the indications of the procedure to include pediatric patients. The aim of this article was to discuss such indications based on the evidence in pediatric solid organ transplantation, reconstructive surgery in children, and VCA in adult patients. Papers published on the outcomes of pediatric solid organ transplantation, growth after replantation of extremities, vascularized autologous tissue transfer, craniofacial surgery, orthognathic procedures, facial fractures, and outcomes after repair of peripheral nerves in children were reviewed. Although the outcomes of solid organ transplantation in children have improved, the transplanted organs continue to have a limited lifespan. Long-term immunosuppressive therapy exposes the patients to an increased lifetime risk of infections, diabetes, hypertension, dyslipidemia, cardiovascular disease, and malignancy. Growth impairment and learning disabilities are other relevant drawbacks, which affect the pediatric recipients. Nonadherence to medication is a common cause of graft dysfunction and loss among the adolescent transplant recipients. Rejection episodes, hospitalizations, and medication adverse effects contribute negatively to the quality of life of the patients. Although normal growth after limb transplantation could be expected, pediatric facial transplant recipients may present with arrest of growth of transplanted midfacial skeleton. Considering the non-life-threatening nature of the conditions that lead to eligibility for VCA, it is suggested that it is premature to extend the indications of VCA to include pediatric patients under the currently available immunosuppressive protocols.

Decision-making in the face of end-stage organ failure

Pediatric solid organ transplantation numbers have been increasing over the years. Research and the medical literature tends to focus on advancing the field and innovation - which often leads to higher risk and more complex procedures. How do we decide when it is too much - too much risk; too much uncertainty? Who makes that decision? Literature is scarce and usually focuses on end-of-life decision-making. This article does not purport to have the answers, but will highlight the depth and breadth of points that must be taken into consideration. There are many factors that contribute to the decision-making in the context of high-risk solid organ transplantation in children. Focus needs to include quality of life in the pediatric context, in addition to survival. End-of-life discussions should be included early in the process. Societal factors must be considered in an era of donor organ shortages. Shared decision-making should be the approach. The key guiding principle is to make a decision about what is best for a child requiring a high-risk transplant based not only on survival, but also on an acceptable quality of life on the background of optimal utilization of a scarce societal resource.

Everolimus in pediatric transplantation

The use of everolimus has recently emerged for solid-organ transplantation in children. This review gives an overview of the relevant studies and clinical trials involving the immunosuppressive effects of everolimus in child organ transplant. The use of everolimus in pediatric organ transplantation is associated with a decrease in calcineurin inhibitor-related toxicity, better renal function, a low number of acute rejections, and an acceptable side-effect profile. Particularly, the use of everolimus reduces the incidence of virus infection and the risk of posttransplant lymphoproliferative disease. Everolimus is an effective agent with several advantages for pediatric solid-organ transplantation. Future prospective, randomized controlled trials will have to be performed in order to validate the findings of these pilot trials.