The efficacy of valganciclovir for prevention of infections with cytomegalovirus and Epstein‐Barr virus after kidney transplant in children

This study evaluated the efficacy of prophylactic ValGCV in preventing CMV and EBV infections in a single‐center pediatric kidney transplant population (2008‐2014). Therapy duration was determined according to donor/recipient serostatus. EBV monitoring was performed using monthly plasma PCR for 18 months post‐transplant and for CMV, monthly for 6 months after prophylaxis cessation. Data were collected on 35 children, median age 10.6 years. There were 15 (42.9%) and 11 (31.4%) recipients seronegative for CMV or EBV, respectively, who received a kidney from a seropositive donor. Prophylaxis was ceased by 6 months in 24 (69%), between seven and 13 months in 10 (29%) children. Fourteen (40%) and eight (23%) children experienced CMV and EBV DNAemia, respectively. Ten of the 14 (71%) episodes of CMV DNAemia occurred in the first 6 months following cessation of prophylaxis. Shorter prophylaxis was associated with increased CMV DNAemia (P = 0.044). There was an inverse correlation between adjusted ValGCV dose and EBV incidence/timing. Neutropenia was more common if ValGCV dosage was ≥10% of the dose predicted (by BSA and creatinine clearance). ValGCV prevents CMV and may modify EBV infection risk. Frequent dosing adjustment for BSA and creatinine clearance is required to optimize safety and efficacy.     

Dynamics of cell‐mediated immune responses to cytomegalovirus in pediatric transplantation recipients

Patel M, Stefanidou M, Long CB, Fazzari MJ, Tesfa L, Del Rio M, Lamour J, Ricafort R, Madan RP, Herold BC. Dynamics of cell‐mediated immune responses to cytomegalovirus in pediatric transplantation recipients.
Pediatr Transplantation 2012: 16: 18–28. © 2011 John Wiley & Sons A/S. Abstract: CMI responses, combined with quantification of CMV DNA (DNAemia), may identify transplantation recipients at risk for invasive disease. PBMC were collected in pediatric transplantation candidates at one, three, and six months post‐transplant in 10 subjects (six renal, three cardiac, one stem cell) and at single time points in eight HC and 14 children greater than one yr post‐transplant (LTTx). Cells were stimulated with anti‐CD3mAb or CMV pp65 peptide pools and responses assessed by IFNG enzyme‐linked immunosorbent spot assay and cytokine secretion. IFNG responses to anti‐CD3mAb were significantly lower pretransplant relative to HC and were further decreased at one and three months post‐transplant, but recovered to levels comparable to HC by six months. Responses to pp65 among CMV‐seropositive recipients followed a similar pattern but recovered by three months. CMV‐seropositive LTTx and HC showed a Th1 cytokine response to pp65 stimulation. Three LTTx subjects developed CMV DNAemia; two demonstrated decreased responses to anti‐CD3mAB (and pp65 in the CMV seropositive subject) at the onset of DNAemia, which recovered as DNAemia resolved. Monitoring CMI in children is feasible and may provide an adjunct biomarker to predict CMV progression and recovery.     

Clinical consequences of human herpesvirus‐6 DNAemia in peripheral blood in pediatric liver transplant recipients

The significance of HHV6 DNAemia after solid organ transplantation has not been fully determined. Our objectives were to determine the prevalence of HHV6 DNAemia in pediatric liver transplant recipients and to describe the associated clinical characteristics and outcomes. This was a retrospective case–control study. Eligible liver transplant patients aged ≤ 18 yr with HHV6 DNAemia were matched with two subjects without HHV6 DNAemia. Matching was by age ± 6 months. Among 154 subjects, 25 patients (16%) had HHV6 DNAemia detected by PCR in whole blood or plasma (M:F ratio = 0.9:1). While 28% of subjects with DNAemia (7/25) had symptoms consistent with HHV6 infection, active infection was detected in only four subjects (2.6% of liver transplant patients). The major symptoms/signs were fever, vomiting, lethargy, splenomegaly, bone marrow suppression, and elevated transaminases. The prevalence of DNAemia due to other herpesviruses in cases vs. controls was EBV 56% vs. 60%, CMV 12% vs. 12%, HHV7 20% vs. 12%; p value is not significant for all pairwise comparisons. HHV6 DNAemia in pediatric liver transplant patients is not an uncommon entity. While the clinical relevance is still not entirely established, active HHV6 infection and attributable symptoms are relatively rare.     

Quantiferon‐Cytomegalovirus assay: A potentially useful tool in the evaluation of CMV‐specific CD8+ T‐cell reconstitution in pediatric hematopoietic stem cell transplant patients

Pediatric HSCT recipients are at high risk for CMV reactivation due to their immature immune system and therapy following transplantation. Reconstitution of CMV‐specific T‐cell immunity is associated with control and protection against CMV. The clinical utility of monitoring CMV‐specific CMI to predict CMV viremia in pediatric HSCT patients using the Quantiferon‐CMV (QIAGEN^®) test was investigated prospectively. Thirty‐seven pediatric allogeneic HSCT recipients were enrolled from 3/2010‐6/2012. CMV viremia was detected via weekly real‐time PCR. The Quantiferon‐CMV test was conducted pretransplant, early after transplantation, 30, 90 , 180 , 270, and 360 days post‐transplantation. The incidence of CMV viremia was 51% (19/37) with half of the episodes within ≤30 days post‐transplant. Fifteen patients showed CMV‐specific immunity (average of 82 days). The cumulative incidence of CMV reactivation in patients who developed CMV‐specific immunity was lower than those who did not (15% vs 53%; P = .023). The ROC statistical analysis showed that the AUC was 0.725 in predicting viremia, for Quantiferon‐CMV test. In this cohort, the Quantiferon‐CMV assay was a valuable method for identifying pediatric HSCT patients at high risk for CMV viremia, suggesting potential clinical utility to individualize patient's management post‐transplant.     

Epstein‐Barr viral load monitoring for diagnosing post‐transplant lymphoproliferative disorder in pediatric liver transplant recipients

This study aimed to investigate the incidence of PTLD in pediatric liver transplant recipients and the risk factors for the development of PTLD. We also determined clinically useful quantitative EBV PCR parameters for aiding in the diagnosis of EBV‐associated PTLD in the pediatric liver transplant recipients at our institute. We reviewed children < 18 years old who had undergone liver transplantations and quantitative analysis of whole blood EBV load at our institute from January 2006 to March 2015. A total of 142 liver transplant recipients were included, and their median age was 1.5 years. Clinically significant high‐level EBV DNAemia ≥ 10 000 copies/mL at least twice was observed in 53.5% and PTLD occurred in 9.9%. Among PTLD group, graft failure and mortality rate were as high as 21.4% and 14.3%, respectively. Deceased donor, presence of high‐level EBV DNAemia, and primary CMV infection following transplant were associated with an increased risk for PTLD in the multivariate analysis. The peak titer at 10 875 copies/mL could be used as a cutoff value with a sensitivity of 92.9% and a specificity of 37.9%; the rate of increase in EBV load suggested a sensitivity of 64.3% and a specificity of 70.9% at the cutoff value of 44 000 copies/mL/week. In conclusion, the incidence of PTLD following liver transplant in children was as high as 10%. PTLD is associated with significant morbidity and mortality. Close monitoring of EBV DNAemia is crucial for the early diagnosis and proper treatment of PTLD in pediatric liver transplant recipients.     

GCV/VCVG prophylaxis against CMV DNAemia in pediatric renal transplant patients: A systematic review and meta‐analysis

CMV disease continues to stand as a significant threat to the longevity of renal transplants in children. More pediatric recipients are CMV‐negative with CMV‐positive donor serologies resulting in a HR mismatch. The length of prophylaxis with GCV or VGCV required to optimally prevent recurrence of CMVDNAemia remains unknown. This study is a meta‐analysis comparing GCV/VGCV prophylaxis regimens provided for <6 months, from 6 to <12 months, and ≥12 months after transplant in order to prevent CMVDNAemia. The search conducted involved PubMed, EMBASE, ISI Web of Science, and Cochrane Central Register from inception through December 2017. Search terms Kidney Transplantation, CMV, GCV, and VGCV provided 204 studies for abstract review. Studies excluded were those which did not itemize pediatric data separately, single case reports, and duplicate studies. Pooled analysis of five retrospective studies and one prospective study identified that there is no statistically significant difference in the incidence of CMV DNAemia when comparing <6 months of prophylaxis and >12 months of prophylaxis (23% and 15%, respectively, P = 0.23). Regardless of the length of prophylaxis, there was no statistical difference in the incidence of CMV DNAemia in the HR patients (6 to <12 months vs <6 months, P = 0.62; 6 to <12 months vs ≥12 months, P = 0.78; ≥12 months vs <6 months, P = 0.83). This study identifies no optimal length of prophylaxis for HR mismatch pediatric renal transplant patients as many develop CMV DNAemia.     

Donor‐to‐recipient weight ratio is a risk factor for hepatic artery thrombosis after whole‐liver transplantation in children under 25 kg

Hepatic artery thrombosis (HAT) following pediatric liver transplantation increases morbidity and risk of graft failure. We performed a retrospective chart review of all patients who underwent deceased‐donor liver transplantation from August 2002 to July 2016. Multi‐organ transplant recipients were excluded. We examined the incidence of HAT at our institution and sought to identify associated donor or recipient risk factors. A total of 127 deceased‐donor liver transplant patients with a median age of 1.7 years (IQR 0.67‐6.7) were identified. Of those, 14 developed HAT, all weighing under 25 kg. Among 100 patients under 25 kg, whole‐liver graft recipients had an odds ratio of 3.98 (95% confidence interval [CI]: 1.03, 15.34; P = .045) for developing HAT compared with split‐liver graft recipients. Within the whole‐liver recipient group under 25 kg, 11 patients developed HAT with a median donor‐to‐recipient ratio (DRWR) of 0.9 (IQR: 0.7‐1.2) compared with a median DRWR of 1.4 (IQR: 1.1‐1.9) for those who did not develop HAT. Multivariate analysis showed DRWR to be an independent risk factor for HAT in patients weighing under 25 kg who received whole organ grafts, with an odds ratio of 3.89 (95% CI: 1.43, 10.54; P = .008) for each 0.5 unit decrease in DRWR. Our results suggest that in recipients under 25 kg 1) split‐liver grafts may have a lower rate of HAT and 2) selecting whole organ donors with a higher DRWR may decrease the incidence of HAT.     

Early post‐operative intravenous tacrolimus in pediatric liver transplant recipients is not superior to oral tacrolimus

We aimed to compare the early results of i.v. with p.o. TAC as a primary immunosuppressant in pediatric patients undergoing LT. This retrospective study enrolled 75 children who underwent LT and received TAC‐steroid regimens as a primary immunosuppressant between September 2011 and October 2015 at our institution. Thirty‐five recipients received TAC i.v. and 40 received TAC p.o. Early results were evaluated and compared, including ACR, EBV, or CMV infection; renal adverse effects; and hospital stay. Comparisons of 90‐day post‐transplant results showed that the rates of overall viral (74% vs 40% P < 0.002), EBV (46% vs 17.5% P < 0.008), and CMV (51% vs 30% P = 0.05) infections were significantly higher in the i.v. than in the p.o. group. Neither regimen has any adverse effects on renal function. There were no between‐group differences in ACR incidence and severity, serum creatinine concentration, and hospital stay. Patient and graft survival rates at 3 months and 1 year did not differ significantly between the two groups. Compared with p.o. treatment, i.v. administration of high TAC concentration did not have beneficial post‐transplant effects on ACR incidence and severity, while increasing the incidence of viral infections in pediatric LT.     

Factors associated with immune hemolytic anemia after pediatric liver transplantation

Immune‐mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single‐center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013. IHA was defined as acute anemia with a positive direct antiglobulin test. Seven cases of immune‐mediated hemolytic anemia were identified (incidence 8.5%). Three cases presented during the first 3 months following LT (early IHA), and 4 presented later (late IHA). All patients with late IHA required rituximab. Using univariate analysis, the following factors were associated with IHA onset: BA (P = .04), younger age (P = .04), and the use of IGL‐1 preservation solution (P = .05). Late IHA was associated with viral infections occurring beyond 3 months following LT, younger age, and BA (P = .01). Overall, CMV infection was associated with the development of both early and late IHA: CMV‐negative recipients who received an organ from a CMV‐positive donor were more likely to develop IHA (P = .035), and de novo CMV infection during the first year post‐LT was associated with late IHA (P = .03). IHA is a rare complication following pediatric LT, occurring more frequently in younger patients and patients with an initial diagnosis of BA. CMV‐negative recipients and patients who experience a de novo CMV infection in the first year following LT seem particularly vulnerable. IGL‐1 preservation solution may be associated with an increased likelihood of developing IHA, a novel finding which warrants further investigation.     

Comparative pharmacokinetics of tacrolimus in stable pediatric allograft recipients converted from immediate‐release tacrolimus to prolonged‐release tacrolimus formulation

This study was a Phase II, open‐label, multicenter, single‐arm, cross‐over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate‐release tacrolimus (IR‐T) to prolonged‐release tacrolimus (PR‐T). In Days ?30 to ?1 of screening period, patients received their IR‐T‐based regimen; during Days 1‐7, patients received study IR‐T (same dose as screening). On Day 7, the first 24‐hours PK profile was taken; patients were then converted to PR‐T (1 mg:1 mg), with a second 24‐hours PK profile taken on Day 14. The primary end‐point was tacrolimus area under the blood concentration–time curve over 24 hours (AUC₂₄); secondary end‐points were maximum concentration C_maxand concentration at 24 hours C₂₄. The predefined similarity interval for confidence intervals (CIs) of least squares mean (LSM) ratios was 80%‐125%. The PK analysis set comprised 74 pediatric transplant recipients (kidney, n = 45; liver, n = 28; heart, n = 1). PR‐T:IR‐T LSM ratio (90% CI) was similar overall for AUC₂₄, _max, and C₂₄, and for kidney and liver recipients for AUC₂₄ (LSM ratio, kidney 91.8%; liver 104.1%) and C₂₄ (kidney 90.5%; liver 89.9%). Linear relationship was similar between AUC₂₄ and C₂₄, and between PR‐T and IR‐T (rho 0.89 and 0.84, respectively), suggesting that stable pediatric transplant recipients can be converted from IR‐T to PR‐T at the same total daily dose, using the same therapeutic drug monitoring method.     

Increased levels of PD‐1 expression on CD8 T cells in patients post‐renal transplant irrespective of chronic high EBV viral load

Studies have identified solid organ transplant recipients who remain asymptomatic despite maintaining CHL. Factors which determine the CHL state remain poorly understood but are likely to involve immunological control of the viral infection. We monitored expression of PD‐1, a marker of T‐cell exhaustion and viral persistence, on CD8 T cells in patients who resolved EBV infection as determined by undetectable EBV DNA (REI) and CHL patients. PD‐1 expression on CD8 T cells was increased in the first year post‐transplant irrespective of EBV outcome, and most CD8 T cells continued to express PD‐1 for up to three yr post‐transplant. Although all patient groups showed similar frequencies of EBV‐specific CD8+ T cells, PD‐1 expression on these cells increased in the post‐transplant groups compared with the pretransplant patients. Functional studies of EBV‐specific CD8+ T cells stimulated with BZLF or LMP2 peptide pools revealed monofunctional IFN‐γ responses. Our results indicate that PD‐1 expression on CD8 T cells post‐transplant may result from factors other than antigenic stimulation.     

Association of post‐transplant donor‐specific HLA antibody with liver graft fibrosis during long‐term follow‐up after pediatric liver transplantation

The aim of this study was to evaluate the significance of post‐transplant DSA as a predictor of liver fibrosis during long‐term follow‐up after pediatric LT. We evaluated the histological findings in 18 LT recipients who underwent liver biopsy after DSA screening. Liver fibrosis was scored based on the METAVIR fibrosis staging. Patients were divided into 2 groups based on histological findings, and clinical characteristics among patients with liver fibrosis were assessed. Of 18 patients, 7 were included in the fibrosis group. No significant between‐group differences were found regarding peritransplant characteristics, including age, sex, primary disease, ABO incompatibility, and immunosuppressive regimen. Episodes of acute rejection and non‐adherence to immunosuppressive drugs were comparable between both groups. The MFI for anti‐DR DSA and positive rate were significantly higher in the fibrosis group (1655 vs 216; P = .019, 86% vs 27%; P = .012, respectively). MFI for anti‐DQ DSA was higher in the fibrosis group, but non‐significantly (2052 vs 384; P = .46). Post‐transplant anti‐DR DSA is associated with graft fibrosis during long‐term follow‐up. This finding seems useful for the implementation of valid histological examinations of liver grafts for patients with higher MFI, especially for anti‐DR DSA, after pediatric LT.     

JC polyomavirus‐specific antibody responses in pediatric kidney transplant recipients

BKPyV is widely recognized in KTRs, but little is known about rates of primary and secondary JCPyV exposure in pediatric KTRs. We evaluated JCPyV exposure in pediatric KTRs using antibody responses in the first 12 months post‐transplant. Of 46 children transplanted between 2009 and 2014, 6 lacked any samples for serologic testing, leaving 40 KTRs for study. JCPyV‐specific IgG and IgM antibodies were measured using a normalized VLP ELISA. Significant JCPyV exposure was defined as IgG seroconversion, increasing IgG levels of >0.5 nOD units, or IgM detection. Of 40 recipients (median age 3.2 years), 11 (27.5%) were seropositive, 20 (50%) seronegative for JCPyV‐IgG, while 9 (22.5%) had no specimen at the time of transplantation, but were confirmed as seronegative in post‐transplant samples. Of 29 (72.5%) at risk, JCPyV‐IgG seroconversion occurred in 15/29 (51.7%) including JCPyV‐IgM in 6 patients (20.7%). Two patients (6.9%) developed only JCPyV‐IgM. Among JCPyV‐IgG‐positive KTRs, six (12.5%) had significant IgG increases. Altogether 23 of 40 patients (57.5%) had serological evidence of primary or secondary JCPyV exposure. In these patients, kidney function tended to be lower during the 2 years of follow‐up, but only one patient lost the graft due to JCPyV nephropathy. Thus, JCPyV exposure is common in pediatric KTR and may present serologically as primary or secondary infection. Although only one case of JC‐PyVAN occurred, a trend toward lower renal function was seen. Dedicated studies of larger cohorts are warranted to define impact of JCPyV in pediatric KTR.     

Cytomegalovirus,adenovirus, and polyomavirus co‐infection among pediatric recipients of allogeneic stem cell transplantation: Characteristics and outcome

Watcharananan SP, Kiertiburanakul S, Piyatuctsanawong W, Anurathapan U, Sungkanuparph S, Pakakasama S, Chantratita W, Hongeng S. Cytomegalovirus, adenovirus, and polyomavirus co‐infection among pediatric recipients of allogeneic stem cell transplantation: Characteristics and outcome.
Pediatr Transplantation 2010: 14:675–681. © 2010 John Wiley & Sons A/S. Abstract: ADV and PMV infection have increasingly been documented as significant complications following allo‐HSCT. Despite increasing recognition, characteristics and outcome of CMV, ADV, and PMV viral co‐infection remain obscured. In this study, a retrospective quantitative PCR analysis of ADV, PMV (BKV and JCV) was performed from pediatric patients’ stored blood samples previously tested for CMV viremia after allo‐HSCT. Clinical and virological characteristics and outcome among patients with and without viral co‐infection were analyzed and compared. From 2001 to 2006, 219 blood samples from 69 patients were studied. Viral DNA was present in 119 samples (52.9%).The proportion of viremia was highest for BKV (30.6%), followed by CMV (20.9%), ADV (9.1%), and JCV (0.5%). Viral co‐infection occurred in 17 patients (24.6%), with CMV/BKV as the most common type (11.6%), followed by CMV/ADV (4.3%) and ADV/BKV (2.9%). From multivariate analysis, factors associated with viral co‐infection were acute GVHD (OR 4.57; 95% CI 1.9–10.96, p = 0.001), level of blood CMV viral load (OR 1.53; 95% CI 1.24–1.89, p < 0.001), and level of blood ADV viral load (OR 1.56; 95% CI 1.05–2.32, p = 0.027). Higher probability of developing viral disease was strongly associated with more types of virus detected in blood (p < 0.001). Significant difference in the causes of death was observed among patients with and without viral co‐infection (p = 0.014). Infection (87.5%) was the major cause of death of patients with viral co‐infection, whereas relapse of hematologic disease (70%) was the major cause of death of patients with mono‐viral infection. Viral co‐infection is a common and significant infectious complication in pediatric recipients of allo‐HSCT. Blood monitoring of CMV, ADV, and BKV is suggested among pediatric patients who develop GvHD or who have rising of CMV or ADV viremia following allo‐HSCT.     

Measles,mumps, rubella (vaccine) and varicella vaccines in pediatric liver transplant: An initial analysis of post‐transplant immunity

Varicella and measles infection represents a significant source of morbidity and mortality for pediatric LT recipients. We evaluated the prevalence and correlates of post‐transplant immunity in pediatric LT recipients previously immunized against measles (n = 72) and varicella (n = 67). Sixteen of seventy‐two (22%) patients were measles non‐immune, and 42/67 (63%) were varicella non‐immune after LT. Median time from LT to titers for measles and varicella was 4.0 and 3.3 years, respectively. In the measles cohort, non‐immune patients received fewer pretransplant vaccine doses (P = 0.026) and were younger at both time of vaccination (P = 0.006) and LT (P = 0.004) compared with immune patients. Upon multivariable analysis, weight > 10 kg at LT (OR 5.91, 95% CI 1.27‐27.41) and technical variant graft (OR 0.07, 95% CI 0.01‐0.37) were independently, significantly associated with measles immunity. In the varicella cohort, non‐immune patients received fewer pretransplant vaccine doses (P = 0.028), were younger at transplant (P = 0.022), and had less time lapse between their last vaccine and transplant (P = 0.012) compared with immune patients. Upon multivariate analysis, time > 1 year from last vaccine to LT was independently, significantly associated with varicella immunity (OR 3.78, CI 1.30‐11.01). This study demonstrates that non‐immunity to measles and varicella is a prevalent problem after liver transplantation in children and identifies 3 unique risk factors for non‐immunity in this high‐risk population.     

Contribution of B7RP‐1/ICOS co‐stimulation to lethal acute GVHD

Fujimura J, Takeda K, Kaduka Y, Saito M, Akiba H, Yagita H, Yamashiro Y, Shimizu T, Okumura K. Contribution of B7RP‐1/ICOS co‐stimulation to lethal acute GVHD.
Pediatr Transplantation 2010: 14:540–548. © 2010 John Wiley & Sons A/S. Abstract: Co‐stimulatory molecules expressed on T cells critically regulate donor T‐cell activation and are implicated in acute GVHD after allogeneic BMT. We here investigated the role of interaction between B7‐related protein‐1 (B7RP‐1) and ICOS in murine acute GVHD model that received T cell‐depleted BM cells and splenocytes. Administration of blocking anti‐B7RP‐1 mAb significantly reduced the lethality and symptoms in acute GVHD. A significant hypo‐responsiveness of splenocytes to host alloantigen was observed in the recipient mice treated with anti‐B7RP‐1 mAb. Moreover, acute GVHD was significantly reduced in the recipients of T cells composed of ICOS‐deficient CD8 T cells and WT CD4 T cells compared with that in the recipients of T cells composed of WT CD8 T cells and ICOS‐deficient CD4 T cells. These results suggested that B7RP‐1/ICOS co‐stimulatory signal plays a role in the activation of alloantigen‐reactive donor T cells, particularly in CD8 T cells, in murine acute GVHD model, and that the blockade of B7RP‐1/ICOS interaction may be useful for selectively manipulating allo‐reactive T cells in the recipients with acute GVHD.     

IGG3 anti‐HLA donor‐specific antibodies and graft function in pediatric kidney transplant recipients

Anti‐HLA DSAs are associated with ABMR and graft loss in KT recipients, yet the influence of DSA IgG subclass on outcomes in pediatric KT recipients is not completely understood. We performed a single‐center retrospective chart review of pediatric KT recipients with anti‐HLA DSAs, aiming to study the association between specific DSA IgG subclasses and graft outcomes, including ABMR and significant graft dysfunction (graft loss or 50% decrease in eGFR). Thirty‐six patients (mean age 15.4y) with DSAs initially detected 1 month‐14.3 years post‐transplantation were followed for a median of 2.8 years. Rates of IgG1, 2, 3, and 4 subclass detection were 92%, 33%, 58%, and 25%, respectively. Twenty‐two patients (61%) had clinical ABMR, whereas 19% had subclinical ABMR, and 13 (36%) experienced significant graft dysfunction. Patients with IgG3+ DSAs had a higher risk of graft dysfunction compared with IgG3‐ patients (52% vs 13%, P = .03). In a multiple Cox proportional regression analysis, the presence of IgG3+ DSA was independently associated with significant graft dysfunction (HR 10.45, 95% CI 1.97‐55.55, P = .006). In conclusion, IgG3 subclass DSAs are associated with graft dysfunction and may be useful for risk stratification and treatment decisions in DSA‐positive pediatric KT recipients.     

Evaluation of the immune function assay in pediatric living donor liver transplantation

The immune function (ImmuKnow) assay is a measure of cell‐mediated immunity based on the peripheral CD4+ T cell ATP activity. The efficacy of ImmuKnow in pediatric LDLT is not well documented. The aim of this study was to assess the correlations between the ImmuKnow and the clinical status in pediatric LDLT recipients. A total of 716 blood samples were obtained from 60 pediatric LDLT recipients (one month to 16 yr of age). The recipient's status was classified as follows: stable, infection, or rejection. The ImmuKnow values in the pediatric LDLT recipients with a clinically stable status had a lower immune response (IQR 85–297 ATP ng/mL) than that previously reported in adults. Meanwhile, the ImmuKnow values of the stable patients were not correlated with age. Furthermore, a significant difference was found in the ImmuKnow values between the bacterial or fungal infection and stable groups, but not between the CMV or EBV infection and stable groups. The ImmuKnow levels in the pediatric LDLT were lower than those observed in the adult LDLT. The proposed reference value is between 85 and 297 ATP ng/mL in pediatric LDLT recipients. We conclude that the ImmuKnow assay could be helpful for monitoring pediatric LDLT recipients with bacterial or fungal infections.     

Using pediatric liver grafts (≤6 yr) for adult recipients: A considerable option?

In LT, the common policy is to allocate pediatric liver grafts to pediatric recipients. Pediatric organs are also offered to adults if there is no pediatric recipient. However, they are rarely accepted for adult recipients. So far, there is no information available reporting outcome of LT in adult recipients using pediatric livers from donors ≤6 yr. In this study, we included nine adult recipients (seven females and two males) who received grafts from children ≤6 yr from January 2008 to December 2013. We evaluated the graft quality, the GBWR and analyzed the recipients’ perioperative course. Laboratory samples and graft perfusion were analyzed. Nine adults with a median age of 49 yr (range: 25–65) and a median weight of 60 kg (range: 48–64) underwent LT with a pediatric donor graft. Median donor age was five yr (range: 3–6). Median GBWR was 1.02 (range: 0.86–1.45). After a median follow‐up of 3.9 yr (range: 11 months–6.6 yr), patient survival was 100%; graft survival was 89%. One patient needed re‐transplantation on the second postoperative day due to PNF. Eight recipients were discharged from the ICU after 2–9 days with a regular graft function. Doppler scans revealed regular flow patterns at any time. Only if denied for pediatric recipients, the use of pediatric livers from donors ≤6 yr for adult recipients is a considerable option.