Pediatric Intestinal Transplant Recipients Research Articles

Postoperative Delirium Screening Characteristics in Pediatric Intestinal, Liver, and Renal Transplant Recipients: Single-Center Retrospective Cohort Study.

To describe and compare the results of delirium screening in the immediate post-transplant PICU admission for pediatric intestinal, liver, and renal transplant recipients. We also examined associations with known and suspected risk factors for pediatric delirium (PD). Retrospective analysis of a single-center cohort, 2016-2022. Twenty-four-bed PICU in a high-volume transplant center. All intestinal, liver, and renal transplant recipients under 23 years old admitted between July 2016 and August 2022. We identified 211 pediatric transplant recipients: intestinal ( n = 36), liver ( n = 78), and renal ( n = 97). Results of the Cornell Assessment for PD during the immediate post-transplant PICU admission were reviewed and patients were categorized into screen positive, screen negative, and unscreened. Corresponding data on known and suspected risk factors for PD were also collected. Data on delirium subtypes were not collected. Screens were available for 156 of 211 patients (74%) who were included in the final analysis. The prevalence of a positive screen by transplant category was: intestine 80% (24/30), liver 75% (47/63), and renal 14% (9/63). A positive screen was associated with younger age, greater duration of mechanical ventilation, and greater PICU length of stay (LOS) in bivariate analysis. In multivariable analysis, age and PICU LOS remained strongly correlated with a positive screen ( p < 0.05). Deep sedation and agitation as categorized by the State Behavioral Scale was associated with a positive screen, as was significant iatrogenic withdrawal symptoms ( p < 0.05). Most patients screened positive by post-transplant days 2 and 3 (58/80 [72%] and 64/80 [80%], respectively). In our 2016 to 2022 experience, we found a high prevalence of positive PD screens in pediatric intestinal and liver transplant recipients in the immediate post-transplant PICU admission. A positive screen was associated with younger age and greater PICU LOS.

Angiotensin II type 1 receptor antibodies and native kidney function in pediatric liver and intestinal transplant recipients.

Angiotensin II type-1 receptor antibody (AT1R-Ab) has been associated with vascular injury and kidney dysfunction in pediatric kidney transplant recipients. The role of AT1R-Ab in the development of chronic kidney disease in pediatric liver and intestinal transplant recipients has not been explored. Twenty-five pediatric intestinal transplant recipients and 79 pediatric liver transplant recipients had AT1R-Ab levels measured at varying time points in the post-transplant period. Estimated glomerular filtration rate (eGFR) was determined using creatinine based CKiD U25 equation and measured at time of AT1R-Ab measurement, at 1year post-AT1R-Ab measurement, at 5years post-AT1R-Ab measurement, and at the most recent routine clinic visit. The prevalence of hypertension and antihypertensive medication use were also evaluated. Younger age at time of AT1R-Ab measurement was associated with AT1R-Ab positivity in liver transplant recipients. There was no association between AT1R-Ab status and change in eGFR, prevalence of hypertension, or use of antihypertensive medications at the described time points. AT1R-Ab positivity was not associated with a decline in eGFR or hypertension in pediatric liver and intestinal transplant recipients. Further studies are needed using other markers of kidney function, such as cystatin C, to validate this finding. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efficacy and safety of recombinant human growth hormone therapy in pediatric intestinal transplant recipients.

Recombinant human growth hormone (rhGH) is widely used to treat growth retardation in children. We aimed to examine the effect of rhGH therapy on growth and its impact on allograft function in children with growth retardation after intestinal transplant (IT). We retrospectively included children younger than 19 years who had received an IT with or without the liver, were diagnosed with growth retardation, and have received rhGH between January 2010 and January 2021. Changes in the patient's anthropometric parameters between baseline and various time points were compared using the paired t-test or Wilcoxon signed-rank test, as appropriate. Seven patients (all males and prepubertal) received rhGH for the median duration of 2.3 years. The median age at rhGH start was 9.5 years. The median growth velocity z-score improved from -0.95 before treatment to 2.3 (p= .04) and 1.9 (p= .06) after 1 and 2 years of treatment, respectively. The median height-for-age z-score significantly improved from -3.4 at rhGH start to -1.3 (p= .005) at rhGH stop and remained above baseline at the last visit (-2.4, p= .002). The change in the first-year growth velocity was negatively correlated with the change in the second-year growth velocity (r= -.90, p= .04). No serious adverse effects or worsening allograft function were observed. Severely growth retarded children after IT could benefit from rhGH treatment. A larger, longitudinal study would be warranted to monitor the long-term effect and safety of rhGH and examine predictors of growth response to rhGH therapy in these pediatric IT recipients.

Sarcopenia prevalence in pediatric intestinal transplant recipients: Implications on post-transplant outcomes.

Sarcopenia has been associated with poor surgical outcomes but has not been studied in pediatric intestinal transplantation. We aimed to determine sarcopenia prevalence in intestinal transplant recipients and the association of sarcopenia with outcomes. We performed a cross-sectional retrospective chart review of intestinal transplant recipients from 2000-present. We estimated total psoas muscle area (tPMA) at L3-L4 and L4-L5 from computed tomography scans prior to or in the immediate peri-operative period. Sarcopenia was defined by tPMA below the 5th percentile for age and sex. We built a Cox-proportional hazards model to determine the association between sarcopenia and patient and graft survival. Of the 56 intestinal transplant recipients included, 36 (64%) were sarcopenic. Graft survival was 79% at one year and 59% at five years. Overall patient survival was 86% at one year and 76% at five years. Peri-transplant sarcopenia was associated with improved graft survival (Hazard ratio 0.42, 95% confidence interval: 0.20-0.88) but not overall survival (Hazard ratio 0.47, 95% confidence interval: 0.19-1.20). In this first report of sarcopenia in pediatric intestinal transplant, we found a high sarcopenia prevalence without an association with worse outcomes. The potential improved graft survival in sarcopenic patients along with underlying mechanisms warrant further exploration.

Multidrug-resistant organisms: A significant cause of severe sepsis in pediatric intestinal and multi-visceral transplantation

Severe sepsis in immunocompromised children is associated with increased mortality. This paper describes the epidemiology landscape, clinical acuity, and outcomes for severe sepsis in pediatric intestinal (ITx) and multi-visceral (MVTx) transplant recipients requiring admission to the pediatric intensive care unit (PICU). Severe sepsis episodes were retrospectively reviewed in 51 ITx and MVTx patients receiving organs between 2009 and 2015. Twenty-nine (56.8%) patients had at least one sepsis episode (total of 63 episodes) through December 2016. Bacterial etiologies accounted for 66.7% of all episodes (n=42), occurring a median of 122.5days following transplant (IQR 59-211.8days). Multidrug-resistant organisms (MDROs) accounted for 73.8% of bacterial infections; extended spectrum beta-lactamase producers, vancomycin-resistant enterococcus, and highly-resistant Pseudomonas aeruginosa were the most commonly identified. Increased mechanical ventilation and vasoactive requirements were noted in MDRO episodes (OR 3.03, 95% CI 1.09-8.46 and OR 3.07, 95% CI 1.09-8.61, respectively; p<.05) compared to non-MDRO episodes. PICU length of stay was significantly increased for MDRO episodes (7 vs. 3days, p=.02). Graft loss was 24.1% (n=7) and mortality was 24.1% (n=7) in patients who experienced severe sepsis. Further attention is needed for MDRO risk mitigation and modification of sepsis treatment guidelines to ensure MDRO coverage for this population.

P-77: Effectiveness of Desensitization Therapy in Pediatric Intestinal Transplant Recipients

Introduction: Donor specific anti-HLA antibodies (DSA) impact negatively on the outcome of the intestinal graft. Although the use of desensitization therapies is becoming more frequent in the last years, issues as “when and how” still remain under discussion. The objective of this study was to evaluate the effectiveness of DSA desensitization in a pediatric intestinal transplant cohort. Methods: We studied retrospectively a cohort of 112 transplants. 14 desensitization procedures in 11 transplants were carried out (figure 1A). Desensitization was performed with different combinations of intravenous immunoglobulin, plasmapheresis and rituximab. Anti-HLA antibodies were tested by Luminex assay. Results: DSA were confirmed in 21 transplants. Desensitization was performed in 10 of them, plus one more retransplant of one of the recipients in the adulthood (figure 1A). Three recipients were desensitized peritransplant because of preformed DSA. Another 3 were desensitized in the context of rejection while 4 more were desensitized when DSA appearance without rejection. In two cases rituximab was used for other purposes (figure 1B). DSA removal was observed in 8 procedures, while in another 2 only class I DSA were cleared. Anti-HLA levels decreased in 2 more patients although DSA persisted. In 2 procedures (corresponding to the same recipient) no changes were observed. Patients with higher antibody levels and class II DSA did not negativize or needed more than one desensitization procedure to do it. No additional rejection episodes were observed in recipients with cleared DSA, who showed same graft survival rates than DSA negative patients. Conclusions: Desensitization treatment in intestinal paediatric recipients was effective in 82% of the transplants (9/11). Class I DSA and those with lower levels were more likely to clear up, which encourages an early desensitization even without any rejection sign.

Valganciclovir for the treatment of cytomegalovirus infections in pediatric intestinal transplant recipients: A case series.

Cytomegalovirus (CMV) is the most common opportunistic infection post-transplant and is associated with significant morbidity and mortality. Currently, there are no FDA dosing recommendations for the use of valganciclovir for the treatment of CMV infections in pediatric patients. This case series describes the use of valganciclovir for the treatment of CMV infections in nine pediatric intestinal transplant recipients (pITR). Retrospective review of pITR between January 2004 and December 2016. The primary outcome was resolution of CMV viremia. Secondary outcomes included time-to-resolution of viremia, relapse rate, incidence of resistance, hematologic adverse effects, rejection, graft loss, and death. Of 214 pITR, ten CMV infections were treated with valganciclovir. One patient was lost to follow-up while on treatment and was not included. Eight (89%) patients had resolution of CMV viremia. The average dose of valganciclovir was 14.3mg/kg (SD 0.82) twice daily. CMV resistance testing was completed in three (33.3%) patients; one patient had a documented mutation requiring leflunomide to clear viremia. Three (33.3%) patients experienced rejection within one month prior to or during treatment for CMV. Six (66.6%) experienced hematologic side effects. No patients died or experienced graft loss. This is the first study to assess the use of valganciclovir for the treatment of CMV in pITR. Based on these results, weight-based dosing of valganciclovir seems to be an appropriate option for the treatment of CMV in pITR. Given limited number of patients reviewed in this case series and the high incidence of hematologic side effects, further investigation is warranted.

Describing universal Strongyloides serologic screening among pediatric intestinal and liver transplant recipients.

Strongyloides spp hyperinfections are a worldwide phenomenon that proves fatal for solid organ transplant recipients. Screening protocols to guide prophylaxis management vary institution to institution from universal to epidemiology driven. Our institution initiated a universal screening protocol regardless of travel history and exposure to ensure no cases were missed. In this study, we describe the outcomes of three Strongyloides sero-positive children whom underwent intestinal or liver transplantation and the experience of universal screening at a tertiary care county hospital in South Florida. Among the 66 intestine and liver pediatric transplant recipients who were screened for Strongyloides antibodies, only three were identified to be sero-positive via the screening mechanism. Two of three had significant epidemiology risk factors. None of the patients reviewed were found to have developed hyperinfection. However, reflecting on the experience represented by our series of pediatric patients, the risk of any complication related to Strongyloides status appears low. Even among this South Florida population whom come from or travel to endemic regions are in contact with sero-positive individuals, very few illustrate sero-positivity. While institutions continue to analyze the cost-benefit of universal testing vs. universal prophylaxis vs. targeted screening, the decision must encompass the patient population, rolling cumulative incidence, and morbidity and mortality related to this disease.

Multiple rare‐earth magnet bead ingestion in a pediatric liver‐small bowel‐pancreas transplant recipient: A case report and lessons learned

Ingestion of rare-earth magnet beads in children has been a public health concern. The potential risk of swallowing multiple magnets is related to magnet attraction to each other, resulting in serious gastrointestinal complications, such as entero-enteric fistula formation, peritonitis, bowel ischemia or necrosis, bowel perforation, and potentially death. We describe the clinical outcome of a 10-year-old child with a liver-small bowel-pancreas transplant who swallowed 26 rare-earth magnetic beads. The patient presented with fever and abdominal pain. Due to difficulty locating the magnets and post-surgical anatomy changes, only 25 magnets were removed endoscopically. After the procedure, she continued to have abdominal distention and fever, leading to further investigation and subsequently an exploratory laparotomy, which confirmed a walled-off perforation. She was treated conservatively with bowel rest and antibiotics, without the need for small bowel graft resection. She recovered well and was eventually discharged on her home enteral feeding regimen. This case emphasizes the importance of taking a good history and having a high index of suspicion to diagnose this dangerous clinical condition, especially in children with an associated predisposing condition for foreign body ingestion, such as developmental delay. Early diagnosis of multiple magnet bead ingestion and prompt detection of its complications in pediatric intestinal transplant recipients could help initiate appropriate intervention and prevent intestinal graft loss.

Factors Impacting on Eating in Pediatric Intestinal-Transplant Recipients: A Mixed-Methods Study.

No empirical data are found examining why eating may be difficult for some children and not others following intestinal transplant. This study aimed to describe the eating behaviors and nutrition intake of intestinal-transplant-recipient children and examine factors that may impact on their eating. Caregivers of all (n = 34) intestinal-transplant recipients <18 years of age in the United Kingdom were invited to participate in this mixed-methods study comprising questionnaires, a 3-day food diary and interviews. Questionnaires included the Children's Eating Behaviour Questionnaire and demographic/nutrition-related items. Analysis was by descriptive statistics using SPSS. Semistructured telephone interviews explored caregiver perceptions of their child's eating. Analysis was thematic. Nine caregivers were recruited and completed the questionnaire and food diary. Eight of these were interviewed. Home tube feeding was required by 77% (n = 7) of children post transplant, 56% (n = 5) were "food avoidant", and median energy intake was 93% (range, 61%-137%) of requirements. The findings revealed complex, interrelated positive and negative medical, caregiver, and child-related influences on eating. Learning to eat at the recommended age and having positive and significant pretransplant eating experiences appeared protective, whereas receiving nothing by mouth and having aversive experiences were barriers. This study provides the first empirical evidence of factors that may influence eating after intestinal transplant in children. The findings suggest promoting eating pretransplant, when the negative physical consequences can be managed, may be protective, and there may be eating-difficulty predictors that could be used to facilitate targeted interventions.

232.4: Viral enteritis in pediatric intestinal transplant recipients.

232.4: Viral enteritis in pediatric intestinal transplant recipients.

Post-transplant lymphoproliferative disorder in pediatric intestinal transplant recipients: A literature review.

Intestinal transplantation is a successful treatment for children with intestinal failure, but has many potential complications. PTLD, a clinically and histologically diverse malignancy, occurs frequently after intestinal transplantation and can be fatal. The management of this disease is particularly challenging. The rejection-prone intestinal allograft requires high levels of immunosuppression, a precondition for PTLD. While EBV infection clearly plays a role in disease pathogenesis, the relatively naïve immune system of children is another likely contributor. As a result, pediatric intestine recipients have a higher risk of developing PTLD than other solid organ recipients. Other risk factors for disease development such as molecular and genomic changes that precipitate malignant transformation are not fully understood, especially among children. Studies on adults have started to describe the molecular pathogenesis of PTLD, but the genomic landscape of the malignancy remains largely undefined in pediatric intestinal transplant patients. In this review, we describe what is known about PTLD in pediatric patients after intestinal transplant and highlight current knowledge gaps to better direct future investigations in the pediatric population.

Long-term results of intestinal transplantation in children: survival after 10 years, intestinal function, quality of life.

The review aims to describe in detail contemporary medical, nutritional, and psychosocial results in pediatric intestinal transplant (ITx) recipients greater than 10 years removed from their transplant, and to highlight significant long-term post-ITx challenges and complications. The review will draw from recent publications in the field, the ITx registry as well as detailed unpublished data from a large, well established single center. The majority of long-term ITx survivors are off parenteral nutrition altogether, but a significant number require supplemental tube feeds to gain weight and grow properly. A number of micronutrient deficiencies are observed in long-term follow-up. Renal insufficiency and posttransplant lymphoproliferative disorder are the most concerning long-term complications. Many require special education, and in certain domains some report lower health related quality of life. For children more than 10 years out from ITx, growth and weight gain are sustained; oral aversion and dependence on supplemental tube feeds remain prevalent issues. Most recipients are successfully managed with frequent outpatient visits and multiple daily medications. Post-transplant lymphoproliferative disorder and chronic kidney disease are long-term concerns. Though many children require special education, most are high functioning and report good health-related quality of life.

Treatment of Epstein-Barr Virus Viremia in Pediatric Intestinal and Liver Transplant Recipients

Treatment of Epstein-Barr Virus Viremia in Pediatric Intestinal and Liver Transplant Recipients

Hepatic Explant Pathology of Pediatric Intestinal Transplant Recipients Previously Treated with Omega-3 Fatty Acid Lipid Emulsion

To evaluate and compare the biochemical and histologic effect of parenteral fish oil lipid emulsion that is rich in omega-3 polyunsaturated fatty acids (O3FAs), Omegaven (Fresenius Kabi AG, Bad Homburg, Germany) with standard omega-6 polyunsaturated fatty acid (O6FA) parenteral nutrition. Comparison of hepatic explant pathology and biochemical outcome on pediatric patients with intestinal failure treated with either parental O3FA or O6FA who had received a liver-inclusive intestine transplant. Seven liver-inclusive intestinal transplants were performed in 7 patients who received O3FA for a mean of 62% ± 13% of total patient life-span (16.1 ± 7.0 months) before transplant. Median total bilirubin fell from 6.9 mg/dL at the start of treatment to 0.7 mg/dL at the time transplant (P < .02), which was a significant decrease compared with the similarly matched O6FA cohort (P = .012). All 7 of the 03FA-treated patients received a liver-inclusive intestinal transplant had advanced fibrosis (stage 3 or 4) noted on explant pathologic examination, despite a resolution of cholestasis at the time of transplant. Histologic inflammatory scores were lower (P = .056) in the 03FA group with similar degrees of advanced fibrosis as in the O6FA group. In a matched comparison of patients undergoing intestinal transplantation with a history of extended O3FA lipid emulsion therapy that successfully reversed hyperbilirubinemia, significant hepatic fibrosis was present in the explanted livers despite a reduction in inflammation. This result confirms concern that the use of O3FA may have a limited role in altering the development of hepatic fibrosis from parenteral nutrition.

Utility of an immune cell function assay to differentiate rejection from infectious enteritis in pediatric intestinal transplant recipients

The Cylex Immune Cell Function Assay measures cell-mediated immunity based on ATP production by stimulated CD4 + cells. We hypothesized that this test would discriminate acute cellular rejection (ACR) from infectious enteritis (IE) in pediatric intestinal transplant (ITx) recipients with allograft dysfunction. We retrospectively analyzed 224 Cylex assays drawn in 47 children who received 53 ITx. Samples were classified as stable, ACR, or IE based on clinical status. ATP values were analyzed using Kruskal-Wallis and t-tests. Overall, there was a statistically significant difference in ATP values based on clinical status (p = 0.03); however, overlap was observed between groups. The median ATP value during ACR was significantly greater than during stable periods (p = 0.02). No difference was seen in IE vs. stability (p = 0.8). The difference in median ATP value in ACR vs. IE approached significance (p = 0.1). Relative to previous levels, ACR episodes were associated with a median ATP increase of 101 ng/mL and IE episodes with a decrease of 3 ng/mL (p = 0.3). These data indicate that the Cylex assay has limited utility in differentiating ACR from IE, largely due to interpatient variability. Following longitudinal intrapatient trends may be an adjunctive tool in discriminating IE from ACR and guiding immunosuppression adjustments in select patients.

Micronutrient deficiencies in pediatric and young adult intestinal transplant patients

Intestinal transplant recipients are at risk of micronutrient deficiency due to the slow process of post-transplant adaptation. Another contributing factor is calcineurin inhibitor-induced renal tubular dysfunction. Patients are typically supplemented with micronutrients during PN; however, the risk of deficiency may persist even after a successful transition to FEN. The goal was to determine the prevalence of, and associated risk factors for, iron, zinc, magnesium, phosphorus, selenium, copper, folate, and vitamins A, D, E, and B12 deficiency in pediatric intestinal transplant recipients after successful transition to FEN. A retrospective review of prospectively collected data from children who underwent intestinal transplantation at Cincinnati Children's Hospital Medical Center was done. Deficiencies of various micronutrients were defined using the hospital reference values. Twenty-one intestinal transplant recipients, aged one to 23yr, who were successfully transitioned to FEN were included in the study. The prevalence of micronutrient deficiency was 95.2%. The common deficient micronutrients were iron (94.7%) and magnesium (90.5%). Age≤10yr (p=0.002) and tube feeding (p=0.02) were significant risk factors for micronutrient deficiencies. Pediatric intestinal transplant recipients have a high risk of micronutrient and mineral deficiencies. These deficiencies were more common among younger patients and those who received jejunal feeding.

Plasmacytoma-like post-transplant lymphoproliferative disorder seen in pediatric combined liver and intestinal transplant recipients

Post-transplant lymphoproliferative disease (PTLD) is a lymphoproliferative disorder secondary to chronic immunosuppression and is the most common malignancy in transplanted patients [Kamdar et al. Curr Opin Organ Transplant, 2011; 16:274-280]. Although PTLD usually presents as B or T cell lymphoma, plasmacytomas have been reported, mostly in the adult population. Six cases of pediatric plasmacytoma-like PTLD have been reported, all of which were treated with vincristine, adriamycin, and dexamethasone (VAD), high dose dexamethasone alone, or dexamethasone + thalidomide [Tcheng et al. Pediatric Blood Cancer, 2006; 47:218-223; Perry et al. Blood, 2013; 8:1377-1383]. We present two cases of pediatric plasmacytoma-like PTLD in combined liver and small bowel transplant patients both successfully treated with bortezomib and dexamethasone based on multiple myeloma protocols [Kyle and Rajkumar, Clin Lymphoma Myeloma, 2009; 9:278-288; Adams and Kaufmann, Cancer Invest, 2004; 22:304-311].

Safety and Efficacy of CMX001 as Salvage Therapy for Severe Adenovirus Infections in Immunocompromised Patients

No therapeutic agent has yet been established as the definitive therapy for adenovirus infections. We describe the clinical experience of 13 immunocompromised patients who received CMX001 (hexadecyloxypropyl cidofovir), an orally bioavailable lipid conjugate of cidofovir, for adenovirus disease. We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 therapy. Virologic response (VR) was defined as a 99% drop from baseline or undetectable adenovirus DNA in serum. The median age of the group was 6 years (range, 0.92-66 years). One patient had severe combined immunodeficiency, 1 patient was a small bowel transplant recipient, and 11 were allogeneic stem cell transplant recipients. Adenovirus disease was diagnosed at a median of 75 days (range, 15-720 days) after transplantation. All patients received i.v. cidofovir for a median of 21 days (range, 5-90 days) before CMX001 therapy. The median absolute lymphocyte count at CMX001 initiation was 300 cells/μL (range, 7-1500 cells/μL). Eight patients (61.5%) had a ≥ 1 log10 drop in viral load after the first week of therapy. By week 8, 9 patients (69.2%) demonstrated a VR, with a median time to achieve VR of 7 days (range, 3-35 days). The change in absolute lymphocyte count was inversely correlated with the change in log10 viral load only at week 6 (r = -0.74; P = .03). Patients with VR had longer survival than those without VR (median 196 days versus 54.5 days; P = .04). No serious adverse events were attributed to CMX001 during therapy. CMX001 may be a promising therapeutic option for the treatment of severe adenovirus disease in immunocompromised patients.

The use of sirolimus as a rescue therapy in pediatric intestinal transplant recipients

To review our experience with SRL as a second-line therapy in our series of 45 SBTx recipients (1997-2009). Retrospective review of five children converted to SRL: 3 M/2 F; median of three yr old (range 20 months-18 yr); rescue indications, adverse events with SRL, resolution of tacrolimus-related side effects, incidence of rejection, PTLD, or GVHD were summarized. Tacrolimus was discontinued (average 13 months after transplant) because of refractory hemolytic anemia in four patients with decreased renal function and because of advanced renal failure and unclear neutropenia in one. PTLD and GVHD had been previously diagnosed in two. Tacrolimus-related side effects disappeared in all five although other immunosuppressants and splenectomy were used simultaneously or later in most of them. Adverse events reported after the conversion were infections (tuberculosis and Pneumocystis carinii in two) and mild hypertriglyceridemia. No rejection, GVHD, or PTLD episode was observed. Four patients are alive with excellent quality of life (median follow-up 18 months). Sirolimus is a safe rescue therapy in SBTx children when tacrolimus is not well tolerated. Renal function and hematologic disorders seem to improve, although other simultaneous strategies could be also involved. Further studies could demonstrate its efficacy as a first-line treatment.