Small Bowel Transplant Patients Research Articles

143: Is there a long term effect on cardiac function in small bowel transplant patients?

143: Is there a long term effect on cardiac function in small bowel transplant patients?

A Case Report of Successful Use of Twice-Daily Letermovir in the Treatment of Resistant Cytomegalovirus in a Small Bowel Transplant Recipient

Cytomegalovirus (CMV) is considered one of the most notable pathogens that affect patients after solid organ transplantation (SOT), especially small bowel transplant patients with a risk of high mortality rate. Its management relies historically on the use of CMV DNA polymerase inhibitors (namely, ganciclovir and valganciclovir). Second-line options include foscarnet and cidofovir, which are highly nephrotoxic and thus less preferred and only used in ganciclovir intolerance or resistance cases. Letermovir is a novel antiviral agent approved for CMV prophylaxis in hematopoietic stem cell transplant, but not for SOT (neither for prophylaxis nor for treatment). We report the first case on the successful use of letermovir in treating CMV disease in a small bowel transplant patient who failed to achieve viral clearance due to ganciclovir resistance and severe intolerance to foscarnet.

369 Therapeutic Plasma Exchange in Small-Bowel Transplant Recipients With Acute Allograft Rejection

Therapeutic plasma exchange (TPE) is used in solid-organ transplant patients to treat antibody-mediated rejection (AMR) by removing donor specific antibodies (DSAs). While ASFA guidelines exist for treating AMR in other solid-organ transplants, no such guidelines exist for small bowel-allograft patients; the benefit of TPE in AMR of small bowel transplant patients has not been studied. Five patients were followed with serial surveillance ileoscopies and allograft biopsies. Tissues were processed using standard protocols (UNMC) for permanent histologic examination. Two H&E stained slides from each biopsy were examined microscopically by gastrointestinal/transplant pathologists for evidence of ACR. To assess for AMR, serial serum DSA levels were obtained via by Luminex LabScreen single antigen bead assay (One Lambda, Canoga Park, CA). Patients were treated with at least five TPE procedures. To determine whether TPE provided benefit, we examined three parameters in the post-apheresis period: DSA presence and strength, histopathologic rejection, and clinical response. All patients developed class I and/or class II DSAs following transplant. No clear change in DSA levels following TPE was seen. Sixty percent of patients (3/5) had histopathologic evidence of acute cellular rejection (ACR) prior to initiation of TPE. Following TPE, biopsies showed no evidence of ACR or did not meet the criteria necessary for evaluation. Management of rejection in small bowel transplant patients, caused by both antibody-mediated and T-cell driven processes, is extremely complex. We examined the impact of performing TPE in patients with histologic and/or clinical evidence of acute rejection. A clear trend in the burden or activity of DSAs, histopathologic improvement of allograft biopsies, or clinical improvement following administration of TPE, was not seen. Thus, in our study, TPE does not appear to have a clear benefit in the treatment of AMR and/or ACR in small bowel rejection. Additional studies will be needed to corroborate our results.

Immunosuppression Nurse Management of Protocol Blood Test Monitoring in Long-Term Follow up of Paediatric Small Bowel Transplant Patients

Immunosuppression Nurse Management of Protocol Blood Test Monitoring in Long-Term Follow up of Paediatric Small Bowel Transplant Patients

Dietary guidance for small bowel transplant patients in the form of dietary education by dieticians and volunteers

Dietary guidance for small bowel transplant patients in the form of dietary education by dieticians and volunteers

Identifying Post Transplant Atypical Hemolytic Uremic Syndrome in Small Bowel Transplant Patients: A Retrospective Analysis

Post transplant thrombotic microangiopathy (PT-TMA) has been recognized for over 25 years. The exact incidence of PT-TMA in small bowel transplant (SBT) patients is unknown with reports varying from 4% to greater than 30%. One of the contributors to the differences in reported occurrence rates is the continued debate regarding the definition of PT-TMA. There is a growing consensus that PT-TMA is complement mediated and therefore can be defined by the same criteria as atypical hemolytic uremic syndrome (aHUS). AHUS is a complement mediated TMA defined by microangiopathic hemolytic anemia, thrombocytopenia (TCP), and end organ damage. We have previously demonstrated that the initiation of eculizumab in post-transplant aHUS (PT-aHUS) has led to improved outcomes in these patients. We believe that establishing reliable diagnostic criteria that can be utilized in the post transplant period will lead to earlier recognition and treatment which will decrease the high mortality rate associated with PT- aHUS. METHODSThis retrospective analysis was performed to evaluate whether we could identify a set of laboratory criteria that would reliably predict patients who are at higher risk of developing of aHUS in the pre-transplant or early post transplant period. Records of the forty-eight patients who underwent SBT at our institution between 2011 and 2013 were reviewed. Laboratory values were collected at three predetermined time points: pre-transplant (during transplant evaluation), 1-month post-transplant, and 6-12 months post-transplant. The criteria we designated for establishing a diagnosis of aHUS included fulfillment of all four of the following parameters at either the 1 month or 6-12 month time point: (1) 25% or greater decrease in platelet count from pre-transplant baseline, (2) serum creatinine increase of greater than 0.3 mg/dL from pre- transplant baseline, (3) haptoglobin of less than 50 mg/dL, and (4) LDH of greater than 250 units/L. Fisher exact test was used to find any statistical difference between the development of PT-aHUS and patient demographics and recorded cause of small bowel failure. RESULTSOne patient was not included in the analysis due to immediate graft failure. Eight of the remaining 47 patients (17%) met the defined criteria for aHUS post transplant. Three of the 8 patients who met the defined aHUS criteria were diagnosed clinically with aHUS and were treated with eculizumab. The remaining 5 who met the defined laboratory criteria for aHUS but were not clinically diagnosed had the following outcomes: 2 patients died due to multi organ failure, 2 have ongoing chronic kidney disease (CKD) and TCP and 1 pediatric patient is doing well. Three patients who did not meet the defined laboratory criteria for aHUS were clinically diagnosed with aHUS and treated with eculizumab. [Display omitted] CONCLUSIONSUtilizing the proposed criteria for defining PT- aHUS the incidence of PT- aHUS was 17% in our series, consistent with prior reports of PT- TMA in SBT patients. This incidence is higher than reported in renal transplant patients, suggesting some unique correlation between SBT and PT-aHUS. Multiple theories can be proposed for the etiology of complement dysregulation: (1) higher doses of immunosuppression (calcineurin inhibitor (CNI) based) required in small bowel recipients may augment endothelial damage and increase complement activity, (2) the transplanted organ itself may be more immunogenic and increase complement activity, (3) CNIs may deregulate T cell-complement homeostasis. The adult patients who met our criteria for PT-aHUS, but were not clinically recognized and treated had worse outcomes indicating a need for early diagnosis and treatment. The finding that an ischemic event as the etiology for small bowel failure is associated with an increased relative risk of developing post transplant aHUS is thought provoking and suggests that in some patients, bowel ischemia may actually be the initial TMA manifestation of aHUS. Pre-transplant evaluation of this subset of patients for the presence of known mutations in complement regulatory genes may be warranted. DisclosuresBroome:Alexion Pharmaceuticals: Honoraria.

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].

Peripheral Blood Gene Expression Analysis in Small Bowel Transplantation: a Pilot Study to Detect Novel Biomarkers of Graft Rejection

Introduction: Long term survival of intestinal transplant patients is hampered by rejection episodes. Currently protocol endoscopy of the graft and biopsies are the only way to predict a rejection episode. Symptoms and clinical findings frequently appear when injury to the graft is irreversible. In this report we present our initial data of putative candidate biomarkers of graft rejection in peripheral blood of intestinal transplant patients. Materials and methods: Gene expression analysis was performed in peripheral blood of intestinal transplant patients. The results were matched with concurrent graft biopsies using bioinformatics. Peripheral blood samples of intestinal transplant patients were collected in Tempus Blood RNA tubes. Concurrent graft endoscopies were performed and graft biopsies were obtained at the time of the blood samples, to match the results of the gene expression analysis with the state of the graft. Whole genome microarray analysis using the Illumina-HT12 Expression beadchip microarray was performed. The gene expression levels in patient samples were compared to those in a pool of healthy volunteers. Bioinformatics analysis was performed using the MetaCore 6.3 software from GeneGo Inc. and the Pathway Studio 7.1 software from Ariadne Genomics. Results: Peripheral blood samples (n=11), of 3 adult patients [transplant day (n=1), no rejection (n=1), minimal rejection (n=2), mild rejection (n=5) and severe rejection (n=2)] were collected. Bioinformatics: Enrichment Analysis: The three most affected pathways differentially expressed in rejection versus a pool of healthy volunteers were related to protein translation: translation initiation, translation elongation termination, and translation in mitochondria, with p-values for all rejection stages in all patients in the 10-4 to 10-18 range. No significant enrichment was observed for these categories in the day of transplant sample. In addition to translation, significant enrichment of several immune response categories was observed in rejection samples. Subsequent gene set enrichment analysis verified these results. The level of enrichment was very high (p-values of 10-5 - 10-60) and increased with the level of rejection in all patients. Genes significantly down-regulated in translation related gene sets included ribosomal proteins RPL13A, RP L22, RPS23, RPL13 and RPL10A, that could be used as potential biomarkers for future experiments. These results were further verified with the use of additional samples of 2 more small bowel transplant patients. Conclusion: In this pilot study we found a list of genes (involved in translation) significantly down-regulated in the peripheral blood of intestinal transplant patients during rejection. Our hypothesis, derived from this project, is that down-regulation of translation in peripheral blood mononuclear cells occurs early during the course of rejection and persists and progresses with the severity of the rejection episode as determined by concurrent graft biopsies.

Characterization of the Ileal Microbiota in Rejecting and Nonrejecting Recipients of Small Bowel Transplants

Small bowel transplantation can be a life-preserving procedure for patients with irreversible intestinal failure. Allograft rejection remains a major source of morbidity and mortality and its accurate diagnosis and treatment are critical. In this study, we used pyrosequencing of 16S ribosomal RNA gene tags to compare the composition of the ileal microbiota present during nonrejection, prerejection and active rejection states in small bowel transplant patients. During episodes of rejection, the proportions of phylum Firmicutes (p < 0.001) and the order Lactobacillales (p < 0.01) were significantly decreased, while those of the phylum Proteobacteria, especially the family Enterobacteriaceae, were significantly increased (p < 0.005). Receiver-operating characteristic analysis revealed that relative proportions of several bacterial taxa in ileal effluents and especially Firmicutes, could be used to discriminate between nonrejection and active rejection. In conclusion, the findings obtained during this study suggest that small bowel transplant rejection is associated with changes in the microbial populations in ileal effluents and support microbiota profiling as a potential diagnostic biomarker of rejection. Future studies should investigate if the dysbiosis that we observed is a cause or a consequence of the rejection process.

Six‐month incidence of bloodstream infections in intestinal transplant patients

Intestinal transplantation has emerged as an established treatment for life-threatening intestinal failure. The most common complication and cause of death is infection. Risk of infection is highest during the first 6 months, as a consequence of maximal immunosuppression, greater than that required for any other organ allograft. We performed a retrospective chart review of all (56) adult and pediatric (<18 years) small bowel transplant patients at our institution between November 2003 and July 2007, and analyzed the 6-month post-transplant incidence of bloodstream infections (BSIs). We evaluated multiple risk factors, including inclusion of a colon or liver, total bilirubin >5, surgical complications, and acute rejection. A BSI developed in 34 of the 56 patients, with a total of 85 BSI episodes. Of these BSI episodes, 65.9% were due to gram-positive organisms, 34.1% gram-negative organisms, and 2.4% due to fungi. The most common isolates were Enterococcus species, Enterobacter species, Klebsiella species, and coagulase-negative staphylococci. Inclusion of the liver and/or a preoperative bilirubin >5 mg/dL appeared to increase the incidence of BSI (P = 0.0483 and 0.0005, respectively). Acute rejection and colonic inclusion did not appear to affect the incidence of BSI (P = 0.9419 and 0.8248, respectively). The BSI incidence was higher in children (P = 0.0058). BSIs are a common complication of intestinal transplantation. Risk factors include age <18, inclusion of the liver, and pre-transplant bilirubin >5. Acute rejection and colon inclusion do not appear to be associated with increased BSI risk.

Autoimmune hemolytic anemia in pediatric liver or combined liver and small bowel transplant patients: a case series and review of the literature

Autoimmune hemolytic anemia (AIHA) occurring after solid organ transplantation is an infrequently reported entity. We describe in this report six cases of AIHA in pediatric liver or combined liver and small bowel transplant patients. We retrospectively identified and reviewed the records of pediatric liver or combined liver and small bowel transplant patients with both serologic and clinical evidence of AIHA. We also performed an English language literature review for prior publications of AIHA occurring after solid organ transplantation. We identified six patients presenting with severe hemolysis 9 months to 14 years after transplantation. All six developed warm AIHA, and two had concomitant cold agglutinins. All except one patient received various therapeutic combinations including steroids, intravenous immune globulin, rituximab, plasmapheresis, splenectomy, and vincristine. Five patients achieved remission 2 weeks to 3 months after presentation. Although tacrolimus has been speculated to play a causative role in the development of AIHA after organ transplantation, our case series demonstrated slightly better outcomes despite continuing tacrolimus compared to published cases where most patients either received significantly reduced doses of tacrolimus or were switched to a different immunosuppressant (83% vs. 76% cumulative literature remission rate). AIHA may occur in solid organ transplant patients at a much higher frequency than previously believed. Hemolysis is often severe and resistant to steroid treatment alone. Thus early diagnosis and institution of aggressive multimodality treatment, including the use of rituximab, may be needed to achieve remission.

Immune-mediated hemolytic anemia in children after liver and small bowel transplantation

Four children who underwent ABO-compatible combined liver and small bowel transplantation developed severe immune-mediated hemolytic anemia. The main management strategies were early and aggressive treatment with steroids, the introduction of rituximab (an anti-CD20 monoclonal antibody), and the use of plasma exchange together with compatible but minimal blood transfusions. Three of the 4 children developed thrombi in the major vessels. In small bowel transplant patients, the early recognition of hemolytic anemia and intensified management with anticoagulation are necessary for the prevention of this complication.

Quantification of Intraepithelial Lymphocytes in Normal Pediatric Small Intestinal Allograft and Native Ilea

Background The small bowel acts as one of the first lines of defense against intraluminal infections and antigenic stimuli. Pediatric small bowel transplant patients are at particular risk from such agents, especially viral enteridities. Quantification of intraepithelial lymphocytes (IEL) in architecturally normal small intestinal mucosal biopsies plays an important role in the diagnosis of conditions such as celiac disease and some viral infections. No studies to date have been done to quantify IEL numbers in pediatric small bowel allografts and in native pediatric ilea. Our study investigated the IEL:enterocyte (EC) ratio in pediatric allograft and native ilea. Methods Hematoxylin and eosin slides from 50 surveillance endoscopic biopsies of small bowel allografts taken from patients <8 years of age and 50 terminal ileal biopsies from aged-matched control populations were reviewed. IEL:EC ratios were averaged from five well-oriented villi in each case. IEC numbers were compared between biopsies from proximal (afferent) and distal (efferent) limbs of double-barrel allograft stomas, as well as native terminal ilea. Results Within small bowel allografts, the average number of villus tip IELs was 1.3/20 ECs (standard deviation [SD] 0.6) in the proximal limb and 1.0/20 ECs in the distal (SD 0.6 P < .01). This value was significantly lower than in the control ilea (2.1/20 EC [SD 0.6]; P < .01, each). The overall distribution of lymphocytes was in a similar pattern throughout the villus with IEL:EC ratios on villus sides from proximal allografts, distal allografts, and native ilea being 1:20, 0.8:20, and 2:20, respectively. Conclusions The results suggest that approximately one to two IEL per 20 ECs at villus tips may represent a “normal” intraepithelial inflammatory cell population in small bowel allografts. The value is lower than that seen in age-matched native ileal biopsies. IEL numbers are significantly higher in the proximal limb compared to the distal limb of double-barrel stomas.

Rotavirus Infection in Adult Small Intestine Allografts: A Clinicopathological Study of a Cohort of 23 Patients

Rotavirus enteritis (RVE) is increasingly recognized as a cause of small bowel allograft dysfunction but its significance in adult patients is unknown. We have studied 23 adult small bowel transplant patients aged 19.8-59 years (mean = 38.2 years), who were presented with diarrhea and tested positive for rotavirus by enzyme-linked immunosorbent assay methods. Serial follow-up biopsies, as well as clinical data, are documented and analyzed. These patients were followed up for an average of 168 days (range 33-534 days). Mean time of rotavirus diagnosis from transplant day was 794 days (range 38-2907 days). Self-limited diarrhea lasting 6-13 days (mean = 9 days) was the main presentation. Sixteen (69.6%) patients developed acute cellular rejection either concurrently with (i.e. six patients) or after (10 patients) RVE, often characterized by prominent mucosal plasmacytosis at an average of 22 days (range 0-94 days) from the day RVE was diagnosed. One-third of patients with acute rejection (i.e. five out of 16) required muromonab-CD3 rescue therapy. Two patients experienced graft loss (one from chronic rejection, another from sepsis). Rotavirus infection is a cause of diarrhea in adult small bowel transplant patients. The infection appeared to trigger cellular rejection that was associated with mucosal plasmacytosis, and sometimes required aggressive rescue therapy.

Human gut microbiome adopts an alternative state following small bowel transplantation

Small bowel transplants provide an exceptional opportunity for long-term study of the microbial ecology of the human small bowel. The ileostomy created at time of transplant for ongoing monitoring of the allograft provides access to samples of ileal effluent and mucosal biopsies. In this study, we used qPCR to assay the bacterial population of the small bowel lumen of 17 small bowel transplant patients over time. Surprisingly, the posttransplant microbial community was found to be dominated by Lactobacilli and Enterobacteria, both typically facultative anaerobes. This represents an inversion of the normal community that is dominated instead by the strictly anaerobic Bacteroides and Clostridia. We found this inverted community also in patients with ileostomies who did not receive a transplant, suggesting that the ileostomy itself is the primary ecological determinant shaping the microbiota. After surgical closure of the ileostomy, the community reverted to the normal structure. Therefore, we hypothesized that the ileostomy allows oxygen into the otherwise anaerobic distal ileum, thus driving the transition from one microbial community structure to another. Supporting this hypothesis, metabolomic profiling of both communities demonstrated an enrichment for metabolites associated with aerobic respiration in samples from patients with open ileostomies. Viewed from an ecological perspective, the two communities constitute alternative stable states of the human ileum. That the small bowel appears to function normally despite these dramatic shifts suggests that its ecological resilience is greater than previously realized.

Intestinal Transplantation Comes of Age

Intestinal transplantation has evolved as a creditable therapeutic option that offers the only chance for cure for patients with intestinal failure who fail parenteral nutrition. The Editors of Transplantation are pleased to publish in this issue the first group of a series of selected articles based on papers presented at the Xth International Small Bowel Transplantation Symposium held in Los Angeles, CA on September 6–8, 2007. All of the articles to be published from this meeting have undergone our standard peer review process. The first articles included in this issue are described below. Additional articles will be published in succeeding issues. The intestine is less tolerant of ischemia than most other transplanted solid organs and, due to frequent significant donor organ size restraints in the majority of intestine recipients, donors are less likely to be procured locally, therefore emphasizing the need to minimize ischemia time. Schaefer et al. (Transplantation 2008; 85: 1300–1310) evaluated the efficacy of intravenous glycine administration in minimizing certain phenomena commonly associated with ischemia–reperfusion injury in a rat intestine model. Their data suggest that perioperative glycine treatment reduces molecular and cellular inflammatory responses within the graft and improves smooth muscle dysfunction posttransplantation. Protocol endoscopy with biopsy has been widely adopted as the standard for small bowel transplant rejection monitoring, but it is invasive, costly, and can be associated with complications. Akpinar et al. studied the use of Fecal Calprotectin levels (FCL) as a possible non-invasive marker for monitoring in small bowel transplant patients (Transplantation 2008; 85: 1281–1286). They present data to show that although no significant FCL difference was found between rejection and inflammation, FCL evolution in individuals could predict rejection days before histopathological diagnosis, suggesting its potential usefulness as a prescreening marker to avoid unnecessary biopsies. Induction immunosuppression is now common practice after intestinal and multivisceral transplantation. Vianna et al. (Transplantation 2008; 85: 1290–1293) describe their experience in 27 patients given antithymocyte globulin, rituximab, and steroids as induction therapy with Tacrolimus and tapered steroids as maintenance. One year patient and graft survival was 81% and 76%. Thirteen patients (48%) experienced 19 episodes of acute rejection; patients with multivisceral grafts experienced fewer episodes of acute rejection. Their data suggest that this induction regimen may have a protective effect against posttransplant lymphoproliferative disease and chronic rejection. Mian et al. (Transplantation 2008; 85: 1287–1289) present a retrospective analysis to determine factors affecting survival of intestinal transplantation in very young pediatric patients. Such patients awaiting intestinal transplantation have a high mortality rate due to long waiting times, scarcity of appropriate size donor organs, and mortality due to sepsis and liver failure. In children under 18 months of age, risks factors affecting survival to intestinal transplantation include small body size and advanced liver disease. No differences in residual small bowel length, presence of the colon, number of line infections or number of central lines were identified in the transplant and not transplanted groups. Intestinal transplantation is only one of a continuous of possible treatments for intestinal failure. Andres et al. (Transplantation 2008; 85: 1294–1299) examined the efficacy of repeat surgical bowel lengthening with the so-called reSTEP procedure (Repeat Serial Transverse Enteroplasty) after previous surgical lengthening procedures. They concluded that in the stable patient who is otherwise unable to wean from parenteral nutrition repeat lengthening via a reSTEP surgery resulted in discontinuation of parenteral nutrition in almost half of a carefully selected group of patients. Most importantly, such repeat procedures did not preclude intestinal transplantation. Anthony Monaco Peter J. Morris

P0601 THE USE OF TACROLIMUS IN ELEVEN CHILDREN WITH STEROID-DEPENDENT/STEROID-RESISTANT ULCERATIVE COLITIS

Introduction: Tacrolimus is a potent macrolide immunosuppressant used widely in liver and small bowel transplant patients. It has been studied in inflammatory bowel disease as an alternative to IV cyclosporin in patients with severe steroid-dependent or steroid-resistant (SD/SR) UC. In this study we examined the efficacy and safety of tacrolimus for induction and maintenance therapy of pediatric SD/SR UC. Methods: This is a retrospective review of 11 patients initially diagnosed with SD/SR UC who were treated with tacrolimus for induction and maintenance of remission. All patients were either steroid-dependent, defined as unable to wean from steroids secondary to diarrhea, bloody stools, or abdominal pain, or steroid-resistant, defined as continued diarrhea or bloody stools despite treatment with IV steroids for at least 4 days. All patients were initially given tacrolimus 0.2 mg/kg/d divided BID with goal trough blood levels between 10 and 15 ng/ml. Remission was defined as HBI <4. All patients were closely monitored for renal toxicity, received PCP prophylaxis, and received oral magnesium supplementation (if necessary). Results: Ten patients responded to therapy within 14 days. Seven of these patients weaned from steroids on average 7.5 weeks from the start of tacrolimus therapy. Four patients achieved prolonged remission and remain in remission on tacrolimus alone (mean follow up 17 months). Five patients achieved remission in two weeks, only to flare either during steroid weaning (3) or following steroid withdrawal (2). Despite maintaining adequate levels of tacrolimus, three patients who responded in the short-term ultimately required colectomy. Two other patients with short-term response to therapy remain symptomatic. One patient achieved remission, but had headaches associated with tacrolimus, and was changed to azathioprine. The last patient had no response to tacrolimus, developed tacrolimus-associated neurotoxicity with seizures, and ultimately required colectomy. One of the patients requiring colectomy developed EBV-associated lymphoproliferative disorder. The main side effect of tacrolimus therapy was neurotoxicity, seen in 3 patients with complaints of seizure (1), tremulousness (3), and headaches (1). No nephrotoxicity or infectious complications were encountered. Conclusion: Prolonged treatment with tacrolimus has significant risks, and should only be attempted by physicians with a strong comfort level with dosing this drug and monitoring for its side effects. This retrospective study indicates that tacrolimus may have a role in pediatric steroid-resistant and steroid-dependent UC for both induction and maintenance of remission.

Rituximab in the treatment of pediatric small bowel transplant patients with posttransplant lymphoproliferative disorder unresponsive to standard treatment

Rituximab in the treatment of pediatric small bowel transplant patients with posttransplant lymphoproliferative disorder unresponsive to standard treatment

Levels of mycophenolic acid and its glucuronide derivative in the plasma of liver, small bowel and kidney transplant patients receiving tacrolimus and cellcept combination therapy

In order to help assess the usefulness of mycophenolate mofetil (MMF) as an immunosuppressive agent in recipients of organs other than kidneys, we measured the trough levels of the active metabolite of MMF, mycophenolic acid (MPA), and its inactive glucuronide derivative (MPAG), in the plasma of liver ( n=83) and small bowel transplant patients ( n=15) receiving MMF in combination with tacrolimus. These levels were compared with a group of renal transplant patients ( n=25) receiving the same drug regimen. All patient groups were otherwise comparable except the small bowel patient group which contained more pediatric patients (average age 18.7±3.9 years), and, therefore, received a higher average drug dose (in mg/kg). Despite this, these patients displayed the lowest levels of MPA of any group (0.39±0.08 μg/ml, P<0.001 vs. 1.10±0.17 μg/ml for liver transplant patients, P<0.001 or 2.46±0.37 μg/ml for renal transplant patients, P<0.001). There were no statistically significant differences in MPAG levels between any of the groups. Although preliminary, these data demonstrate significant transplanted organ-specific differences in MMF pharmacology and/or bioavailability, and suggest the need for separate evaluation of MMF dosing for each transplant type.