Isolated cutaneous mucormycosis in a pediatric renal transplant recipient

Mucormycosis is a rare and potentially life‐threatening infection, typically affecting immunocompromised hosts. We report a case of an adolescent boy who developed primary isolated cutaneous mucormycosis in the early period following kidney transplantation. Surgical excision was performed using intraoperative fungal staining to obtain clear margins, followed by topical and systemic antifungal therapy. A skin graft was then applied to the excised area with good healing, and the patient made a full recovery.     

Donor‐derived strongyloidiasis in a Saudi pediatric kidney transplant recipient: A case report and mini‐review

S. stercoralis infection has been identified as a donor‐derived infection in cases of solid organ transplant among recipients with no prior risk factor for parasitic exposure. Worldwide and regional reports from the adult kidney transplant population highlight this indirect method of infection and caution about delayed diagnosis, severe complications, and death related to donor‐derived S. stercoralis infection. We report a deceased‐donor‐derived S. stercoralis infection in a 12‐year‐old Saudi girl who underwent kidney transplantation. This is the first pediatric case reported outside the United States of America. Although she presented with mild bouts of gastrointestinal symptoms, the need for additional immune suppression put her at risk of serious complications. A literature review highlights the importance of awareness about S. stercoralis infections and complications in kidney transplant recipients, pretransplant screening of donors based on risk assessment, and the challenges with treatment availability and duration in this vulnerable population.     

Fecal microbiota transplantation in a toddler after heart transplant was a safe and effective treatment for recurrent Clostridiodes difficile infection: A case report

Pediatric recipients of SOT have a significantly increased risk of Clostridiodes (formerly Clostridium) difficile infection (CDI), which is associated with adverse outcomes after SOT. Alterations to the intestinal microbiota community structure increase the risk of CDI. FMT is a safe and effective treatment for recurrent CDI in immunocompetent children and adults. While there are increasing data that FMT in immunosuppressed patients is safe and effective without increased risk of infection, data regarding safety and efficacy of FMT in children after SOT are limited. To our knowledge, we report the youngest immunocompromised patient to undergo FMT and the third overall case of FMT in a child after HTx. Our patient presented with five episodes of rCDI in 6 months, and 16S rRNA genetic analysis revealed significant loss of overall microbiota community structure and diversity prior to FMT compared with a donor and a healthy, age‐matched control. After FMT, marked and prolonged (at least 16 months) shifts in the recipient microbiota community structure and diversity were evident, approaching that of donor and healthy, age‐matched control. FMT was well tolerated, restored microbial diversity without any graft or transplant complications, and prevented further rCDI episodes after more than 4 years of follow‐up.     

Pediatric heart transplant from an incompletely treated influenza A‐positive donor

There is a shortage of pediatric donor hearts for waitlisted children, and yet nearly 50% of organs offered are not transplanted. Donor quality is often cited as a reason for declining organs offered from donors infected with influenza, presumably due to concern about disease transmission at transplant leading to severe disease. We previously described an excellent outcome after heart transplant from a donor infected with influenza B that had been treated with a complete course of oseltamivir. In this report, we describe a similar outcome after transplantation of an organ from an influenza A‐positive donor with symptomatic disease incompletely treated with oseltamivir. Due to the availability of effective antiviral treatment, we suggest that influenza A is also a manageable donor infection that need not preclude heart placement.     

BK virus nephropathy in a pediatric heart transplant recipient with post‐transplant lymphoproliferative disorder: A case report and review of literature

BKV is known to cause allograft failure in kidney transplant recipients. It has been recently recognized to cause native kidney nephropathy in non‐kidney transplant recipients. This is a case report BKVN in a 15‐yr‐old HTx recipient who had PTLD and a review of pediatric cases in the literature. The patient was diagnosed with BKVN +189 months after transplantation and died thirty days after diagnosis of BKVN. We identified five other cases of BKVN in pediatric non‐kidney solid organ transplantation, of which all were HTx recipients. Overall, outcome was poor and BKV clearance was not achieved with reduction of immunosuppression and with current therapies. We strongly recommend that pediatric HTx recipients be tested for BKV infection if there is evidence of kidney dysfunction. We also recommend that they have an annual screening for BKV viruria and viremia with the assessment of kidney function.     

Sudden death in a pediatric heart transplant recipient with peripheral eosinophilia and eosinophilic myocardial infiltrates

Eosinophilia has been rarely reported in pediatric heart transplant recipients and has been suggested to play a role in graft rejection. We report a case of a young female patient with peripheral blood eosinophilia who died suddenly 2 years following ABO‐incompatible heart transplantation. She was found at autopsy to have myocardial infiltration of not only T‐lymphocytes and macrophages expected in acute cellular rejection but also of eosinophils, B‐lymphocytes, and plasma cells indicating myocarditis.     

Low donor‐to‐recipient weight ratio does not negatively impact survival of pediatric heart transplant patients

Tang L, Du W, Delius RE, L’Ecuyer TJ, Zilberman MV. Low donor‐to‐recipient weight ratio does not negatively impact survival of pediatric heart transplant patients.
Pediatr Transplantation 2010: 14:741–745. © 2010 John Wiley & Sons A/S. Abstract: A major limitation to success in pediatric heart transplantation is donor organ shortage. While the use of allografts from donors larger than the recipient is accepted, the use of undersized donor grafts is generally discouraged. Using the UNOS database, we wanted to evaluate whether using smaller donor hearts affects the short‐ and long‐term survival of pediatric heart transplant patients. A retrospective analysis of data entered into the UNOS database from April 1994 to May 2008 was performed. Pediatric heart transplant recipients (ages 0–18 yr) with DRWR <2.0 were identified and divided into two groups: Low‐DRWR (<0.8) and Ideal‐DRWR (0.8–2.0). Patients’ demographics, pretransplant diagnoses, age at transplantation, severity of pretransplant condition, and rate of complications prior to hospital discharge after transplantation were noted. Fisher’s exact, chi‐square, and Wilcoxon rank sum tests were used to compare patients’ baseline characteristics. Kaplan–Meier curves and Cox proportional hazard regression were used to compare patients’ survival and to identify independent risk factors for outcomes. There were 3048 patients (204 with Low‐ and 2844 with Ideal‐DRWR). The Low‐ratio group patients were older (8.3 vs. 6.9 yr; p = 0.001), there was a slight male predominance in the Low‐DRWR group (p = 0.055). The Low‐DRWR group had longer transplant wait time than the Ideal‐DRWR group (97 vs. 85 days; p = 0.04). The groups did not differ in race, primary diagnoses, severity of pretransplant condition (medical urgency status, need for ventilation, inotropic support, ECMO, nitric oxide, or dialysis, the PVR for those with bi‐ventricular anatomy), or post‐transplant complications (length of stay, need for inotropic support, dialysis, and rate of infections). The Low‐DRWR patients had less episodes of acute rejection during the first‐post‐transplant month. Infants with DRWR 0.5–0.59 had lower 30‐day survival rate (p = 0.045). There was no difference in short‐ and long‐term survival between the patients with DRWR 0.6–0.79 and DRWR 0.8–2.0. Use of smaller allografts (DRWR 0.6–0.8) has no negative impact on the short‐ and long‐term survival of pediatric heart transplant patients.     

Bone mineral status in pediatric heart transplant recipients: A retrospective observational study of an “at risk” cohort

Sachdeva R, Soora R, Bryant JC, Seibert JJ, Blaszak RT, Frazier EA. Bone mineral status in pediatric heart transplant recipients: A retrospective observational study of an “at risk” cohort.
Pediatr Transplantation 2010:14: 383–387. © 2009 John Wiley & Sons A/S. Abstract: There is a paucity of literature assessing the burden of bone loss in PHT recipients. We sought to describe the bone mineral status in PHT recipients by doing a retrospective medical record review of those who underwent evaluation of BMD when clinically indicated. Data collected included patient demographics, BMD evaluations, serum calcium, phosphorus, alkaline phosphatase, cumulative steroid dose, osseous complications and their management. Of 149 PHT recipients, 26 underwent BMD evaluation. This evaluation was done at a median of 3.4 yrs after PHT. There total serum calcium, phosphorus and alkaline phosphatase were similar at transplant and BMD study. The median BMD Z‐scores were: whole body ?0.09 (1.5 to ?5.13) and lumbar spine ?1.1 (1.5 to ?5.16). Bone loss (Z‐score 相似文献   

Successful treatment of a classic Hodgkin lymphoma‐type post‐transplant lymphoproliferative disorder with tailored chemotherapy and Epstein–Barr virus‐specific cytotoxic T lymphocytes in a pediatric heart transplant recipient

CHL type is the least common major form of EBV‐related PTLD but rarely occurs in pediatric recipients; development of CHL subsequent to other PTLD subtypes in the same transplant recipient is even more unusual. Because of its rarity, indications on the best treatment strategy are limited. Patients have been mostly treated with standard HL chemotherapy/radiotherapy, and prognosis seems more favorable than other monomorphic PTLDs. Herein, we describe a pediatric case of EBV‐associated, stage IV‐B, CHL arising in a heart allograft recipient eight yr after diagnosis of B‐cell polymorphic PTLD. The patient was successfully treated with adjusted‐dose HL chemotherapy and autologous EBV‐specific CTL, without discontinuation of maintenance immunosuppression. At two yr from therapy completion, the patient is in CR with stable organ function. With this strategy, it may be possible to reproduce the good prognostic data reported for CHL‐type PTLD, with decreased risk of organ toxicity or rejection.     

A fatal case of bortezomib‐induced lung toxicity in a young adult heart transplant recipient

Bortezomib is approved for the treatment of multiple myeloma but increasingly used in heart transplant (HTx) recipients with antibody‐mediated rejection (AMR). Severe pulmonary toxicity is a rare complication in multiple myeloma patients treated with bortezomib, but has not been described in a solid organ transplant recipient. A 20‐year‐old man 7 years post‐HTx presented with acute rejection with hemodynamic compromise. Endomyocardial biopsy showed mixed rejection (ISHLT grade 2R‐3R acute cellular rejection (ACR) and pAMR 1 (I+) with diffuse C4d staining). Two new high MFI circulating MHC class‐II donor‐specific antibodies (DSA) were detected. Treatment included corticosteroids, antithymocyte globulin, plasmapheresis, IVIG, rituximab, and bortezomib (1.3 mg/m²). Due to rebound in DSA, a second course of bortezomib was started. Thrombocytopenia and peripheral neuropathy prompted a 50% dose reduction during the 2nd course. Shortly after the 3rd reduced dose, the patient developed hypoxemic respiratory failure. Bronchoscopy revealed pulmonary hemorrhage with negative infectious studies. Chest CT showed bilateral parenchymal disease with bronchiectasis and alveolar bleeding. Despite treatment with high‐dose steroids, severe ARDS ensued with multisystem organ failure. The patient expired 23 days after the final dose of bortezomib. Post‐mortem lung histology revealed diffuse alveolar damage, pulmonary fibrosis, and hemorrhage. Cardiac histology showed resolving/residual ACR 1R and pAMR 1 (I+). While rare, bortezomib‐induced lung toxicity (BILT) can occur in HTx recipients and can carry a high risk of mortality. Drug reaction and immediate drug withdrawal should be considered in patients who develop respiratory symptoms, though optimal management of BILT is unclear.     

Early changes in cell‐free DNA levels in newly transplanted heart transplant patients

Heart transplantation is a well‐established therapy for end‐stage heart failure in children and young adults. The highest risk of graft loss occurs in the first 60 days post‐transplant. Donor fraction of cell‐free DNA is a highly sensitive marker of graft injury. Changes in cell‐free DNA levels have not previously been studied in depth in patients early after heart transplant. A prospective study was conducted among heart transplant recipients at a single pediatric heart center. Blood samples were collected from children and young adult transplant patients at three time points within 10 days of transplantation. DF and total cell‐free DNA levels were measured using a targeted method (myTAI_HEART). In 17 patients with serial post‐transplant samples, DF peaks in the first 2 days after transplant (3.5%, [1.9‐10]%) and then declines toward baseline (0.27%, [0.19‐0.52]%) by 6‐9 days. There were 4 deaths in the first year among the 10 patients with complete sample sets, and 3 out of 4 who died had a late rise or blunted decline in donor fraction. Patients who died trended toward an elevated total cell‐free DNA at 1 week (41.5, [34‐65] vs 13.6, [6.2‐22] P = .07). Donor fraction peaks early after heart transplant and then declines toward baseline. Patients without sustained decline in donor fraction and/or elevated total cell‐free DNA at 1 week may have worse outcomes.     

Tacrolimus‐associated hemolytic uremic syndrome in a pediatric heart transplant recipient

HUS is a well‐known entity primarily associated with bacterial infection and is characterized by a classic triad of anemia, thrombocytopenia, and kidney injury. Its atypical form has been associated with calcineurin inhibitors and has been extensively discussed in renal transplantation. We present a case of tacrolimus‐associated HUS in a pediatric heart transplant recipient, which we believe to be previously unreported in the literature.     

Clinical significance of anti‐HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis

While VAD use in pediatric patients has previously been associated with anti‐HLA antibody production, the clinical significance of these antibodies is unclear. We investigated the clinical impact of anti‐HLA antibodies associated with VAD use in a large cohort of pediatric HTx recipients. From 2004 to 2011, pediatric cardiomyopathy patients post‐HTx (N=1288) with pre‐HTx PRA levels were identified from the United Network for Organ Sharing database. PRA levels were compared between VAD patients and those with no history of MCS. Incidence of rejection and overall survival were compared between VAD and non‐MCS groups after stratification by PRA and age. VAD recipients were more likely to produce anti‐HLA antibodies than non‐MCS patients (25.5% vs 10.5% had PRA>10%, P<.0001). Sensitized VAD patients (PRA>10%) had a higher incidence of rejection within 15 months of HTx compared to sensitized non‐MCS patients (57.1% vs 35.9%, P=.02). There was no intergroup difference in 15‐month mortality. Among pediatric cardiomyopathy patients supported with a VAD, the presence of anti‐HLA antibodies prior to HTx is associated with an increased risk of rejection. The mechanism of the association between VAD‐associated antibodies and early rejection is unclear and warrants further investigation.     

Variability in donor selection among pediatric heart transplant providers: Results from an international survey

There is considerable variability in donor acceptance practices among adult heart transplant providers; however, pediatric data are lacking. The aim of this study was to assess donor acceptance practices among pediatric heart transplant professionals. The authors generated a survey to investigate clinicians’ donor acceptance practices. This survey was distributed to all members of the ISHLT Pediatric Council in April 2018. A total of 130 providers responded from 17 different countries. There was a wide range of acceptable criteria for potential donors. These included optimal donor‐to‐recipient weight ratio (lower limit: 50%‐150%, upper limit: 120%‐350%), maximum donor age (25‐75 years), and minimum acceptable left ventricular EF (30%‐60%). Non‐US centers demonstrated less restrictive donor selection criteria and were willing to accept older donors (50 vs 35 years, P < 0.001), greater size discrepancy (upper limit weight ratio 250% vs 200%, P = 0.009), and donors with a lower EF (45% vs 50%, P < 0.001). Recipient factors were most influential in the decision to accept marginal donors including recipients requiring ECMO support, ventilator support, and highly sensitized patients with a negative XM. However, programmatic factors impacted the decision to decline marginal donors including recent programmatic mortalities and concerns for programmatic restrictions from regulatory bodies. There is significant variation in donor acceptance practices among pediatric heart transplant professionals. Standardization of donor acceptance practices through the development of a consensus statement may help to improve donor utilization and reduce waitlist mortality.     

Alemtuzumab (Campath‐1H) therapy for refractory rejections in pediatric heart transplant recipients

Despite substantial improvements in survival after pediatric heart transplantation, refractory rejection remains a major cause of morbidity and mortality. We have utilized ALE (Campath‐1H) in six consecutive patients with refractory rejection. These rejection episodes persisted despite conventional treatment, which included intravenous methylprednisolone, rituximab, immunoglobulin G, and antithymocyte globulin. In our series, after ALE therapy, LV SF increased from 22%±5% to 33%±5% (P=.01). However, in our series, ALE therapy neither led to persistent LV function recovery nor could it prevent subsequent antibody‐mediated rejection.     

Disseminated fungal infection by Aureobasidium pullulans in a renal transplant recipient

Renal transplant recipients are on long‐term potent immunosuppressive therapy, which makes them highly vulnerable to opportunistic fungal infections. Dematiaceous, or dark‐pigmented saprophytic fungi, are being increasingly seen as opportunistic pathogens of mycoses in immunosuppressed patients. One of these is Aureobasidium pullulans, which is a black yeast‐like dematiaceous fungus found ubiquitously in the environment that can cause various opportunistic human infections. Most infections occur by traumatic inoculation, such as keratitis and cutaneous lesions; disseminated mycoses are very rare and occur only in severely immunocompromised patients. We report a case of disseminated fungal infection due to A. pullulans in a pediatric patient who underwent renal transplant. The use of voriconazole and vacuum‐assisted closure along with surgical drainage most likely contributed to the patient's positive outcome.     

Allosensitization does not alter post‐transplant outcomes in pediatric patients bridged to transplant with a ventricular assist device

Patients supported with a VAD are at increased risk for sensitization. We aimed to determine risk factors for sensitization as well as the impact of sensitization on post‐transplant outcomes. The UNOS database (January 2004–June 2014) was used to identify patients (≤18 yrs) supported with a durable VAD. Rates and degree of sensitization in the VAD cohort were calculated. Post‐transplant survival was determined comparing outcomes of sensitized vs. non‐sensitized patients. There were 3097 patients included in the study; 19% (n = 579) were bridged with a VAD. Of these, 41.8% were sensitized vs. 29.9% of the patients who were not bridged with a VAD (p < 0.001). VAD was an independent predictor of sensitization (OR 2.05 [1.63–2.57]; p < 0.001). There was no difference in sensitization based on device type (continuous vs. pulsatile flow, p = 0.990). Post‐transplant survival rates between the sensitized and non‐sensitized VAD patients were not different, including patients with a PRA >50% and VAD patients with a positive DSC (p = 0.280 and 0.160, respectively). In conclusion, pediatric VAD patients are more likely to be sensitized, but there was no difference in sensitization based on device type. In addition, sensitization does not appear to impact outcomes.