The incidence of autoimmune hemolytic anemia in pediatric hematopoietic stem cell recipients post‐first and post‐second hematopoietic stem cell transplant

The reported incidence of post‐allogeneic HSCT AIHA was between 4.4% and 6% following a single transplant. Cord blood transplantation, T‐cell depletion, and chronic GvHD are significantly associated with post‐transplant AIHA. During an 11‐yr period, data for 500 pediatric HSCT recipients were eligible for evaluation of the incidence of AIHA post‐first and post‐second transplants. Demographic, transplant, and post‐transplant‐related variables were analyzed. Twelve of 500 (2.4%) recipients at a median of 273 days and seven of 72 (9.7%) recipients at a median of 157 days developed AIHA post‐first and post‐second HSCT, respectively. Post‐first HSCT, none of the MRD recipients developed AIHA (0/175 MRD vs. 12/325 other donors, p = 0.04). Four of 12 required a second HSCT to control the AIHA. After the second HSCT, MUD was significantly associated with the development of AIHA. No other variables were associated with the post‐second transplant AIHA. The incidence of AIHA post‐first and post‐second HSCT was less than the reported. The increased incidence of AIHA among recipients of second HSCT is most likely due to the profound immune dysregulation. A much larger, prospective study would be needed to evaluate the incidence, complications, and management of post‐transplant AIHA.     

Management and prevention of cytomegalovirus infection in paediatric hematopoietic stem cell transplant (HSCT) recipients: A binational survey

CMV infection is an important cause of morbidity and mortality among HSCT recipients. Optimal strategies for prevention and management of CMV disease following haematopoietic stem cell transplantation remain uncertain. We conducted an online survey of Australasian paediatric allogeneic HSCT centres on management and prevention of CMV disease in this patient group. We asked for one response from a representative of the HSCT team and one from a representative of the ID team at each centre. All Australasian paediatric HSCT centres responded to our survey. Management of CMV in pre‐transplant setting was consistent between centres. All centres used a pre‐emptive strategy to prevent CMV disease, guided by quantitative CMV PCR. In the post‐transplant post engraftment setting, all centres recommended using ganciclovir (5mg/kg/dose twice daily) as a first‐line therapy for CMV reactivation or disease, with treatment duration of 14 days, provided declining CMV quantitative PCR. There was substantial variability of practice between centres in post‐transplant management of CMV reactivation, especially during the pre‐engraftment phase. Similarly, there was lack of uniformity in indication, dosing and duration of maintenance therapy. Divergence was noted between responses from HSCT and ID physicians within centres. This study identifies areas of uniformity and others of great variability in prevention and management strategies for CMV in paediatric HSCT. Data on CMV infection and management in HSCT patients should be routinely collected as part of prospective trials to inform guidelines and improve prevention and treatment of this important complication.     

Multiple viral infections post‐hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts

Olkinuora HA, Taskinen MH, Saarinen‐Pihkala UM, Vettenranta KK. Multiple viral infections post‐hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts.
Pediatr Transplantation 2010:14:242–248. © 2009 John Wiley & Sons A/S. Abstract: Delayed immune reconstitution and the ensuing opportunistic infections among children following hematopoietic stem cell transplantation (HSCT) are associated with increased treatment‐related morbidity and mortality (TRM). We retrospectively evaluated the impact of viral infections on the posttransplant recovery of pediatric recipients of stem cell grafts as a reflection of their posttransplant immunoreconstitution in a single institution setting. The case histories of 124 children (during 1/1999‐9/2006) were reviewed for infectious episodes, and correlated with their respective clinical parameters. Patients with a high risk for CMV received prophylaxis, but failures in the prophylaxis were common (40%). 110/124 (89%) of these allogeneic patients had at least one viral reactivation/clinical infection posttransplant. In this group of pediatric patients chronic GVHD (P<0,001) and secondary graft failure were significantly (P=0,001) associated with early (during the first 100 days post HSCT), multiple (≥ 2) viral infections. Our data indicate that viruses are common pathogens among pediatric recipients of allogeneic stem cell grafts. In this group of patients multiple viral infections early on seem to reflect an even more severe degree of immunological derangement in the recipient and identify a group of patients with an increased risk of chronic GVHD and secondary graft failure.     

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.     

Human herpesvirus‐6 viremia is not associated with poor clinical outcomes in children following allogeneic hematopoietic cell transplantation

HHV‐6 is an evolving pathogen in the field of AlloHCT. However, the impact of HHV‐6 on AlloHCT outcomes remains to be elucidated. We studied the incidence and clinical impact of HHV‐6 viremia in children following AlloHCT. One hundred consecutive children were monitored weekly by plasma PCR for the first 180 days following AlloHCT for HHV‐6, CMV, EBV, and ADV. HHV‐6 viremia was defined as plasma PCR >1000 viral copies/mL. The median age was nine yr. Following AlloHCT, 19% (95% CI 11.3–26.7%) of patients had HHV‐6 viremia, with the highest incidence of reactivation (14/19, 73%) occurring during day +15‐day +98. The proportion of platelet engraftment by day +180 was lower in patients with HHV‐6 viremia (58%) than in those without HHV‐6 viremia (82%), p = 0.028. Delay in neutrophil and platelet engraftment was not associated with HHV‐6 viremia in multivariate analysis. Similarly, HHV‐6 viremia was not associated with TRM in multivariate analysis (p = 0.15). In summary, HHV‐6 viremia is prevalent in pediatric AlloHCT recipients. Based on our study results, we recommend that HHV‐6 PCR should only be performed on clinical suspicion.     

The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation

Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy‐one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele‐matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele‐matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31). PCR screening for BK virus, adenovirus, Epstein‐Barr virus, parvovirus B19, human herpesvirus 6, and CMV were performed routinely weekly. Infections between 0‐30, 31‐100, and 101 days‐2 years were identified separately. BK virus and CMV reactivations were significantly low in MRD transplant patients (P = .046 and P < .0001, respectively), but incidences of all virus infections between MUD1, MUD2, and haplo‐HSCT were found statistically not different. The OS was found to be affected by having one or multiple virus infection (P = .04 and P = .0008). Despite antiviral prophylaxis and treatments, post‐transplant viral infections are associated with reduced overall survival. Haplo‐HSCT is comparable with MUD transplantation in the setting of viral infections. A larger study group and prospective studies are needed to confirm this observation.     

Incidence,risk factors,and outcome of blood stream infections during the first 100 days post‐pediatric allogeneic and autologous hematopoietic stem cell transplantations

Bloodstream infections (BSI) are a frequently observed complication after hematopoietic stem cell transplant (HSCT). Retrospective analysis of clinical and microbiological data during the first 100 days from 302 consecutive pediatric patients who underwent HSCT for a malignant disease at our institute between January 2013 and June 2017. A total of 164 patients underwent autologous and 138 allogeneic HSCT. The overall incidence of BSI was 37% with 92% of infectious episodes occurring during the pre‐engraftment phase. Gram‐positive bacteria (GPB) accounted for 54.6% of the isolated pathogens, gram‐negative bacteria (GNB) for 43.9%, and fungi for 1.4%. Coagulase‐negative staphylococci and Escherichia coli were the most commonly isolated GPB and GNB, respectively. Forty‐five percent of GNB were extended‐spectrum beta‐lactamase producers and 21% were multidrug‐resistant organisms. Fluoroquinolone resistance was 92% and 68%, among GPB and GNB, respectively. Risk factors for BSI in univariate analysis were allogeneic HSCT, delayed time to engraftment more than 12 days, previous BSI before HSCT, and alternative donor. In multivariate analysis, only HSCT type (allogeneic vs autologous P = .03) and previous BSI within 6 months before HSCT (P = .016) were significant. Overall survival at day 100 was 98% and did not differ significantly between patients with and without BSI (P = .76). BSI is common in children undergoing HSCT for malignant diseases. Allogeneic HSCT recipients and previous BSI within 6 months before HSCT are associated with increased risk of post‐transplant BSI. With current supportive measures, BSI does not seem to confer an increased risk for 100‐day mortality.     

Impact of active antibody‐mediated rejection treatment on donor‐specific antibodies in pediatric kidney transplant recipients

AMR is a major cause of graft loss after kidney transplantation. We evaluated a retrospective cohort of 13 pediatric kidney transplant patients diagnosed with active AMR. All 13 patients were treated with plasmapheresis (PP), IVIg, and rituximab. Anti‐HLA DSAs were measured at the time of transplantation, AMR diagnosis, 30 days post‐rejection treatment, 90 days post‐rejection treatment, and 24 ± 12 months post‐AMR. A total of 68 DSAs were identified from 13 patients at the time of active AMR diagnosis. The primary objective of this study was to differentiate treatment response rates between class I and class II anti‐HLA DSA post‐AMR treatment. Overall, DSAs were significantly reduced at 30 days, and the reduction was sustained at 90 days post‐treatment, even for class II anti‐HLA and strongly positive DSAs. A significant difference between class I and class II anti‐HLA DSA was observed at 30 days; however, between class significance was lost at 90‐day follow‐up due to continued class II anti‐HLA DSA treatment response. Low DSA strength was predictive of treatment response. eGFR demonstrated significant improvement 90 days after AMR diagnosis compared to the initial value at the time of AMR, and the effect was sustained for 12 months. These results suggest that the AMR treatment is effective in pediatric kidney transplant recipients with an early diagnosis of active AMR across both class I and class II anti‐HLA DSAs.     

BK viremia and nephropathy in pediatric renal transplant recipients

The renal survival rate of pediatric renal transplant recipients (pRTR) has improved with the use of modern immunosuppressive agents; however, the incidence of post‐transplantation viral infection has increased. This study investigated the incidence of BK viremia and BK viral–associated nephropathy (BKVAN) in pRTR. One‐hundred‐and‐thirty‐four pRTR were divided into two groups: group 1 (n = 20, 14.9%) comprised those who were prospectively followed with longitudinal analyses after renal transplantation in the time period from May 2007 to June 2008, while group 2 (n = 114, 85.1%) cross‐sectional study of those who were transplanted from January 1994 to April 2007. The mean ages at transplantation in groups 1 and 2 were 10.6 ± 4.7 years and 7.8 ± 4.5 years, respectively. BK viremia was detected in four (20.0%) patients in group 1, and seven (6.1%) in group 2 (P = 0.04), with increased incidence associated with induction therapy. The median time to detection of BK viremia after transplantation was 44 days in group 1 and 142 days in group 2. BKVAN was diagnosed in three patients (two in group 1 and one in group 2). All three patients diagnosed with BKVAN were receiving tacrolimus, mycophenolate mofetil, and corticosteroids as maintenance immunosuppression. Reducing immunosuppression resulted in reduced BK viremia. Monitoring for BK viremia and BKVAN is important in pRTR being treated with the current immunosuppressive regimen. The first line of treatment for BK viremia remains careful reduction of immunosuppression and close monitoring of renal allograft function.     

Autoimmune hemolytic anemia and immune thrombocytopenia following hematopoietic stem cell transplant: A critical review of the literature

Autoimmune cytopenias (AIC) post‐hematopoietic stem cell transplant (HSCT) are rare but exceptionally challenging complication. We conducted a comprehensive literature review and identified a pooled incidence of post‐HSCT autoimmune hemolytic anemia and/or immune thrombocytopenia of 2.66% (SE = 0.27) in pediatric patients. Nonmalignant disease, unrelated donor transplant, peripheral or cord blood stem cell source, conditioning regimen without total body irradiation, and presence of chronic graft‐versus‐host disease were prominent risk factors. Treatment was highly variable, and cytopenias were commonly refractory. AIC represent a significant post‐HSCT complication. We report here the incidence, risk factors, and possible biology behind the development of AIC in pediatric post‐HSCT patients.     

Unusual presentations of BK virus infections in pediatric renal transplant recipients

BKV has emerged as a significant pathogen in the field of transplantation, predominantly causing BKV nephropathy in renal transplant recipients and hemorrhagic cystitis in HSCT recipients. However, case reports describe more diverse complications, and we too present three unusual cases of BKV infections in pediatric renal transplant recipients. First, we describe a case of biopsy‐proven renal damage secondary to BKV prior to the onset of viremia, demonstrating that BKV nephropathy can occur without preceding viremia. We also present two renal transplant recipients with persistent BK viruria, one with BKV‐associated hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we conclude that BKV manifestations may be more diverse than previously thought and suggest clinical utility in urine BKV qPCR testing in specific transplant recipients.     

BK polyomavirus infection in pediatric heart transplant recipients: a prospective study

BKV infection and nephropathy complicate pediatric HTx, but the incidence and time course of the disease are unknown. We assessed the incidence of BKV infection and its association with kidney dysfunction in pediatric HTx recipients. A single center prospective study compared pediatric (<18 years) HTx recipients, with and without BKV infection, who received an allograft between September 2013 and December 2014. Screening of urine for BKV was performed prior to transplant, and at week 1, and at months 3, 6, 9, 12, and 15 months post‐transplantation. Serum for BKV DNA was assayed if BK viruria was present. Statistics included Fisher's exact test and Student's t test. Twelve patients were enrolled. Two patients were removed per parent request. Two (20%) had BK viruria and one (10%) had BK viremia. No patients developed BKVN. BK viruria was present within 2 months following transplantation. There were no identifiable risk factors for BKV infection and no statistically significant difference in renal function between the groups; however, there was a trend toward worsening renal function in those with BKV infection. BKV infection can occur early following heart transplantation. Screening for BK viruria should be considered in HTx recipients.     

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.     

Hematopoietic stem cell transplantation without in vivo T‐cell depletion for pediatric aplastic anemia: A single‐center experience

For young patients, HLA‐MRD HSCT is the first‐line treatment of SAA. However, due to China's birth control policy, few patients could find suitable sibling donors and HLA‐MUD. More and more transplantation centers have used Haplo‐D as the donor source for young adult and pediatric patients. However, studies with larger amount of pediatric patients are rare. We retrospectively analyzed the data of children with AA who were treated with allogeneic HSCT and compared the therapeutic efficacy of Haplo‐HSCT and MRD/MUD group. A total of 62 patients were enrolled. Implantation was successfully performed in 58 patients. There was no significant difference in the time for reconstruction of hematopoietic function between patients in the two groups. Thirty‐two had grade I‐IV aGVHD with incidence of 51.61%. The incidence of aGVHD was 79.41% for patients in the Haplo‐HSCT, significantly higher than that of 17.86% for patients in the MRD/MUD group (P < .01). However, the incidence of cGVHD was not significantly different between patients in the two groups (26.47% vs 10.71%, P = .09), the incidence of CMV infection was 28.57% and 52.94% for patients in the MRD/MUD and Haplo group, respectively, showing no significant difference (P = .053). The incidence of EBV infection was 47.06% for patients in the Haplo group and 28.57% for patients in the MRD/MUD group, showing no significant difference (P = .11). However, the 3‐ and 5‐year cumulative OS and FFS rates showed statistically significant difference in the two groups, P = .012 and .045, respectively. Compared to Haplo‐HSCT, MRD/MUD is more economic. In this study, we achieved good Haplo transplantation results. The incidences of cGVHD and CMV/EBV were not significantly different between Haplo group and MRD/MUD group. Although OS and FFS of the Haplo group were not as good as those of the MRD/MUD group, it is still acceptable as an alternative treatment under emergency.     

Evaluation of the current post‐transplantation Human Leukocyte Antigen antibody screening in pediatric renal transplant recipients

The necessity of post‐transplant monitoring for donor‐specific antibodies (DSAs) is unclear. This study evaluates the clinical relevance of post‐transplantation donor‐specific HLA antibodies in pediatric renal transplant recipients, aiming at better stratification of patients at risk of graft dysfunction and better recommendations for post‐transplant monitoring. A cohort of 68 pediatric kidney recipients, involving 76 transplantations between 2004 and 2014, was studied retrospectively. All patients were screened for HLA antibodies at 1, 3, 6, and 12 months after transplantation and yearly thereafter. Samples testing positive were further analyzed to detect DSA. A biopsy was performed on clinical indication. We studied the baseline characteristics of the patients with biopsy, with DSA, and with rejection. We assessed the effect of post‐transplant DSA on clinical outcome, including antibody‐mediated acute rejection and GFR decrease. In our cohort, the prevalence of DSA was 19% (13/68 transplantations). Most patients with HLA antibodies after transplantation were DSA‐positive (76%; 13/17). A clear association between DSA and subsequent rejection was found. At the end of the study period, a significantly lower GFR was found in patients with biopsy, DSA, or rejection. Based on our observations, we recommend routine post‐transplantation screening for HLA and DSA. The presence of DSA justifies a renal biopsy even in the absence of clinical signs of rejection.     

New‐onset diabetes after pediatric heart transplantation: A review of the Pediatric Heart Transplant Study

NDT is a well‐defined complication after solid organ transplantation. Little has been published describing the incidence, risk factors, and effect on outcome after pediatric heart transplantation. We performed a retrospective evaluation of pediatric patients from the PHTS registry from 2004 to 2014. Group comparison, associated factors, incidence using Kaplan‐Meier method, and risk factor and outcome analysis for NDT at 1 year post‐transplant. Of the 2185 recipients, 1756 were alive and followed at 1 year. Overall freedom from NDT was 98.9%, 94.7%, and 92.6% at 1, 5, and 10 years, respectively. Patients with NDT were more likely to be black (non‐Hispanic; P = 0.002), older at time of transplant (P < 0.0001), and have a higher BMI percentile at time of transplant (P < 0.0001). Adjusted risk factors for NDT at 1 year were older age at transplant (years; >12 years, OR: 8.8 and 5‐12 years, HR: 8.0), obese BMI percentile at time of transplant (OR: 3.8), and steroid use at 30 days after transplant (OR: 4.7). Though uncommon, NDT occurs with a constant hazard after pediatric heart transplant; it occurs more often in older patients at transplant, those who are of black race, those who are obese, and those who use steroids. Therefore, targeted weight reduction and selective steroid use in at‐risk populations could reduce the incidence of early NDT. Further data are needed to determine the risk imparted by transplantation, factors that predict late‐onset NDT, and whether NDT alters the outcome after transplant.     

CD154‐expressing CMV‐specific T cells associate with freedom from DNAemia and may be protective in seronegative recipients after liver or intestine transplantation

Cell‐mediated immunity to CMV, if known, could improve antiviral drug therapy in at‐risk children and young adults with LT and IT. Host immunity has been measured with CMV‐specific T cells, which express IFNγ, but not those which express CD154, a possible substitute for IFNγ. CMV‐specific CD154+ T cells and their subsets were measured with flow cytometry after stimulating PBL from recipient blood samples with an overlapping peptide mix of CMV‐pp65 antigen for up to 6 hours. CMV‐specific CD154+ T cells co‐expressed IFNγ in PBL from three healthy adults and averaged 3.8% (95% CI 3.2%‐4.4%) in 40 healthy adults. CMV‐specific T cells were significantly lower in 19 CMV DNAemic LT or IT recipients, compared with 126 non‐DNAemic recipients, 1.3% (95% CI 0.8‐1.7) vs 4.1 (95% CI 3.6‐4.6, P < .001). All T‐cell subsets demonstrated similar between‐group differences. In logistic regression analysis of 46 training set samples, 12 with DNAemia, all obtained between days 0 and 60 from transplant, CMV‐specific T‐cell frequencies ≥1.7% predicted freedom from DNAemia with NPV of 93%. Sensitivity, specificity, and PPV were 83%, 74%, and 53%, respectively. Test performance was replicated in 99 validation samples. In 32 of 46 training set samples, all from seronegative recipients, one of 19 recipients with CMV‐specific T‐cell frequencies ≥1.7% experienced DNAemia, compared with 8 of 13 recipients with frequencies <1.7% (P = .001). CMV‐specific CD154+ T cells are associated with freedom from DNAemia after LT and IT. Among seronegative recipients, CMV‐specific T cells may protect against the development of CMV DNAemia.     

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.     

Size‐reduced lung transplantation in children – an option worth to consider!

Benden C, Inci I, Weder W, Boehler A. Size‐reduced lung transplantation in children – an option worth to consider!
Pediatr Transplantation 2010: 14:529–533. © 2009 John Wiley & Sons A/S. Abstract: Lung transplantation is an accepted therapy for pediatric end‐stage lung disease. However, there is a shortage of suitable donor organs. Therefore, the use of downsized lung allografts seems a valuable option. We report our experience of downsized pediatric lung transplantation in comparison with standard full‐size pediatric lung transplantation over one decade. Pediatric recipients undergoing downsized or standard lung transplantation were included (January 1997–December 2006). We compared pretransplant clinical data and surgical and post‐operative complications and post‐transplant outcome. Ten pediatric lung transplants were performed (median patient age 15.6 yr [12.3–17.8]). Nine of 10 patients had CF. Five patients underwent standard full‐size lung transplantation; five had downsized lung transplants. “Downsized” recipients had significantly lower median height and weight Z‐scores. Donor/recipient length difference was significantly greater in the “Downsized” Group (p < 0.05). All patients had comparable post‐transplant functional outcome without additional surgical complications or morbidities in “downsized” recipients. Median post‐transplant survival was 65 months (5–77) in the “Standard” Group compared to 86 months (64–121) in the “Downsized” Group (p = 0.1). Our data suggest that downsized lung transplantation in pediatric recipients may have post‐transplant outcomes comparable to full‐size lung transplantation without significant complications.     

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.