First Year Of Transplantation Research Articles

Intestinal transplantation in children: current status.

Intestinal transplantation (IT) is the least common form of organ transplantation; however, it has shown exceptional growth and improvement in graft survival rates over the past two decades mainly due to better outcomes achieved during the first year of transplantation (76 % at 1 year), due to improvement in surgical techniques and the development of better immunosupressive therapies as we understand more about the relationship between the recipient and host immune system. There are still ongoing issues with chronic rejection and long-term survival. Intestinal transplantation is still an acceptable therapy for patients with intestinal failure (IF), but it is generally reserved for patients who develop severe and life-threatening complications despite standard therapies, or those who are not able to maintain a good quality of life. The purpose of this review is to describe the current status, indications, outcomes and advances in the field of intestinal transplantation.

Computational chemical imaging for cardiovascular pathology: chemical microscopic imaging accurately determines cardiac transplant rejection.

Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR) spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients’ biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures.

BK virus nephropathy is not always alone.

Introduction: BK virus associated allograft nephropathy (BKVAN) is an important cause of allograft lost that often occurs in the first year of transplantation. The state of over immunosuppression also predispose these patients to various opportunistic viral infection Objectives: This research aimed to study the renal transplanted patients for BK viremia and BKVAN. Patients and methods: This observational study was conducted between January 2013 to December 2014 to study the renal transplanted patients for BK viremia and BKVAN. In our center patients received combination of de-sensitization therapy including antithymocyte globulin (ATG), rituximab (RITU), basiliximab, therapeutic plasma exchange, and methylprednisolone (MTP), in high risks or only MTP therapy in immunologically low risk patients. Results: Of total number of 26 patients (20-52 years, M/F 17/9), seven patients received ATG and seven patient received intensive desensitizing protocols, BKVAN and BK viremia happened in three and two patients in above groups subsequently, only one patient developed BKVAN in low risk group. We also observed; cytomegalovirus (CMV) and parvovirus B19 infection and hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA) and endocarditis in our patients with BKVAN and BK viremia. Conclusion: Awareness about the possibility of BK virus nephropathy and appropriate immunosuppression minimization are crucial components of management. Consideration of other opportunistic infections and specific syndromes are also very important.

Independent risk factors for early urologic complications after kidney transplantation.

Urologic complications are the most frequent technical adverse events following kidney transplantation (KTX). We evaluated traditional and novel potential risk factors for urologic complications following KTX. Consecutive KTX recipients between December 1, 2006 and December 31, 2010 with at least six-month follow-up (n = 635) were evaluated for overall urologic complications accounting for donor, recipient, and transplant characteristics using univariate and multivariate logistic regression. Urologic complications occurred in 29 cases (4.6%) at a median of 40 d (range 1-999) post-transplantation and included 17 ureteral strictures (2.6%), five (0.8%) ureteral obstructions due to donor-derived stones or intraluminal thrombus, and seven urine leaks (1.1%). All except two complications occurred within the first year of transplantation. Risk factors for urologic complications on univariate analysis were dual KTX (p = 0.04) and renal artery multiplicity (p = 0.02). On multivariate analysis, only renal artery multiplicity remained significant (aHR 2.4, 95% confidence interval 1.1, 5.1, p = 0.02). Donation after cardiac death, non-mandatory national share kidneys, donor peak serum creatinine > 1.5 mg/dL or creatinine phosphokinase > 1000 IU/L, and donor down time were not associated with urologic complications. Our data suggest that donor artery multiplicity is an independent risk factor for urologic complications following KTX.

The mortality risk with graft function has decreased among children receiving a first kidney transplant in the United States

Mortality has decreased in children with end stage kidney disease. Decreases in mortality during dialysis and improved graft survival contributed to this improvement. However, it is unknown if rates of death with graft function have also improved. We measured this in first transplant recipients under 21 years old registered in the USRDS. Cox models were used with a time-dependent renal replacement therapy modality variable to estimate the hazard ratios for death with graft function associated with a 1-year increment in the calendar year of transplant. There were 157,201 person-years of observation among 17,468 recipients with 82.2% of study time during graft function and 17.8% during dialysis after graft failure. There were 2003 deaths (12.7 deaths/1000 person-years) overall of which 985 occurred with graft function (7.6 deaths/1000 person-years) and 1018 occurred during dialysis after graft failure (36.1 deaths/1000 person-years). Each 1-year increment in calendar year of first transplant was associated with a significantly lower risk of death, both over all observation (HR 0.97 [0.96, 0.98]) and focusing on time with graft function (HR 0.98 [0.97, 0.99]). Living donation was significantly associated with better survival while dialysis after graft failure was associated with a much higher mortality risk (HR 4.85 [4.40, 5.35]) compared with graft function. Thus, the risk of death with graft function has decreased in children receiving a first kidney transplant. Increasing living donation and minimizing dialysis may further improve outcomes.

A Successful Transplantation from Maastricht Category-4 Non-Heart Beating Donor

The shortage of available organs is the limiting factor for kidney transplantation (Ktx). One of the strategies to increase access to Ktx is the use of non-heart beating (NHB) donors. We herein present a successful Ktx from an NHB (Maastricht Category-4) donor. The donor was a 21-year-old woman who had brain death due to cerebrovascular accident. She had severe hypotension for three hours despite 30 μg/kg/min dopamine infusion, followed by cardio-pulmonary arrest just before the operation began. Cardio-pulmonary resuscitation was consequently initiated and continued during the operation. Donor organ harvesting (hepatectomy and bilateral nephrectomy) was performed after direct aortic cannulation. The warm ischemia time was 35 minutes. The recipient was a 54-year-old man who had undergone hemodialysis for four years. There were 3/6 mismatches, and the lymphocyte cross-match was negative. The induction immunosuppressive was anti-thymocyte globulin, followed by tacrolimus/ MMF/steroid after the 12th day. He had delayed graft function and hemodialysis was required at the third and sixth days. The urine output gradually increased and sCr slowly declined afterwards and he discharged with sCr 1.5 mg/dl on the 24th day. At the first year of transplantation, he is in good clinical condition with a stable baseline sCr of 1.5 mg/dl. NHB donors can be an alternative and important source to expand the kidney donation pool, and successful long-term outcomes favor this modality.

Clinical implications of intracoronary imaging in cardiac allograft vasculopathy.

Despite improvements in survival and outcomes, cardiac allograft vasculopathy (CAV), a unique form of coronary artery disease, continues to remains the leading cause of late morbidity and mortality in heart transplantation (HTx) recipients and accounts for ≈30% of all-cause mortality in this group.1 CAV can develop at any stage after HTx with an incidence of ≈7% within the first year of transplantation and 30% within 5 years.2 CAV is clinically silent and asymptomatic in its initial stages, making early diagnosis particularly challenging. Annual coronary angiography is currently the imaging modality of choice for screening and surveillance of graft coronary arteries for signs of CAV.3 However, low sensitivity of coronary angiography for detecting early-stage CAV necessitates the use of more advanced intracoronary imaging to diagnose the disease in its initial stages. Recent advances in invasive coronary imaging such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have shown promising results in detecting subangiographic CAV, predicting prognosis and guiding therapy.4–6 The current article reviews the present state and future directions for the use of intracoronary imaging in the diagnosis, prognosis, and treatment of CAV. Several invasive and noninvasive imaging tools have been used to screen and diagnose CAV. Some of the noninvasive tests such as dobutamine stress echocardiography, myocardial perfusion imaging (exercise and pharmacological), cardiac MRI, and coronary computed tomography angiography have been studied extensively for this purpose.7–9 Although these noninvasive tests are highly specific for angiographic CAV, they lack sensitivity in detecting subangiographic CAV.7 The diffuse nature of CAV may result in inability to identify differences in radionuclide uptake in myocardial scintigraphy testing. A 2014 meta-analysis by Wever-Pinzon et al9 demonstrated that compared with coronary angiography, coronary computed tomography angiography was 97% sensitive for detecting any CAV. However, when …

Mycobacterial infection and the impact of rifabutin treatment in organ transplant recipients: a single-center study.

Tuberculosis (TB) is a frequently encountered infection among organ transplant recipients in developing countries, and the incidence of infection after the first year of transplantation is considerably high. In this study, the impact of rifabutin treatment on organ transplant recipients with TB infection was evaluated with respect to the trend of infection, management and outcome. The medical records of 26 post-transplant patients who received an organ transplant between 2004 and 2012 and later diagnosed with TB of different organs were reviewed retrospectively. We retrieved data regarding clinical features as well as treatment and outcomes. The median time interval between transplantation and TB was 36 months (IQR 12-101 months). The most common form of infection was pulmonary/pleural TB. All our subjects received rifabutin instead of rifampin in the anti-TB treatment regime as rifabutin is a less-potent inducer of cytochrome P-450. All patients responded satisfactorily to the treatment and maintained excellent allograft function. Moreover, we did not have any mortality among our recipients. Drug-induced hepatitis was observed in nine (35%) patients. Rifabutin is an excellent alternative medication to rifampin in the setting of TB management. Hepatotoxicity is a potential risk for treatment because of the potential additive toxicity of immunosuppressive drugs.

Role of Hypertension and Anaemia in Left Ventricular Remodelling in Patient with Renal Allograft in the First Post-transplant Year.

Background:Hypertension (HT) and renal anaemia (RA) are well-established markers of cardiovascular risk in patients with chronic kidney disease (CKD). They appear to be the stimuli for left ventricular hypertrophy (LVH), who significantly participates in cardiac complications in uremic patients. Hypertension is extremely common after kidney transplantation (KTx) and it has been observed in up to 75% of patients. The prevalence of post-renal transplant anaemia (PTA) is variable (up to 30%) and several factors such as graft function contribute towards its pathophysiology.Aim:The aim of this study was to analyze the impact of blood pressure and anaemia on LV remodelling in first year after transplantation comparing echocardiographic findings before and twelve months after transplantation had done.Methods:In five years retrospective-prospective study we followed up 30 patients with renal allograft in first post-transplant year. During the study values of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), blood hemoglobin (Hgb), serum creatinine and creatinine clearance were monitored monthly.Results:Before transplantation (Tx) 86% of patients had HT, and RA was confirmed in all patients. Normal echocardiographic findings had 33% of patients and 67% of patients had echocardiographic sings of LVH. Before renal transplantation group with LVH had statistically higher the mean values of blood pressure (MBP) (p=0.053) compared to group with diastolic (LVDDF) (p=0.0047) and systolic-diastolic dysfunction (LVSDDF) (p=0.0046). The values of SBP and DBP positively correlated with LV mass index (LVMI) in the group of patients with LVH (p=0.0007 and p=0.0142). The values of Hgb was statistically higher in group with normal LV mass index compared to LVH (p=0.019), with negative correlation between LVMI and values of Hgb in the patients group with LV hypertrophy (p=0.009). After the first year of transplantation, 63% of patients showed normal LV mass index and 37% remained with echocardiographic findings of the LVH. The values of SBP and values of Hgb in both groups, as well as values of DBP in group of LVH were statistically different in compare with data before transplantation (p<0.05). The positive echocardiographic remodelling of LV significantly correlated with the increase of Hgb values (p=0.05), but without significant correlation with the decrease of the mean SBP and DBP.Conclusion:These results confirmed that positive echocardiographic remodelling of left ventricle after successful renal transplantation is complex process depended on many risk factors and elimination of uremia- related factors is a priority.

Acute Cholecystitis Is a Common Complication after Allogeneic Stem Cell Transplantation and Is Associated with the Use of Total Parenteral Nutrition

The incidence and risk factors for acute cholecystitis after allogeneic hematopoietic stem cell transplantation (HSCT) are not well defined. Of 644 consecutive adult transplants performed at our institution between 2001 and 2011, acute cholecystitis occurred in the first year of transplant in 32 patients (5.0%). We conducted 2 retrospective case-control studies of this population to determine risk factors for cholecystitis after HSCT and to evaluate the performance of different methods of imaging to diagnosis cholecystitis in patients undergoing HSCT compared with non-HSCT patients. In the HSCT population, development of cholecystitis was associated with an increased 1-year overall mortality rate (62.5% versus 19.8%, P < .001). The risk of developing cholecystitis was higher in patients who received total parenteral nutrition (TPN) (adjusted odds ratio, 3.41; P = .009). There was a trend toward more equivocal abdominal ultrasound findings in HSCT recipients with acute cholecystitis compared with nontransplant patients (50.0% versus 30.6%, P = .06). However, hepatobiliary iminodiacetic acid (HIDA) scans were definitively positive for acute cholecystitis in most patients in both populations (80.0% of HSCT recipients versus 77.4% of control subjects, P = .82). In conclusion, acute cholecystitis is a common early complication of HSCT, the risk is increased in patients who receive TPN, and it is associated with high 1-year mortality. In HSCT recipients with findings suggestive of acute cholecystitis, especially those receiving TPN, early use of HIDA scan may be considered over ultrasound.

Total costs and clinical outcome of hematopoietic stem cell transplantation in adults with leukemia: comparison between reduced-intensity and myeloablative conditioning.

The total cost of hematopoietic stem cell transplantation (HSCT) as well as the financial impact of HSCT on the house holds of patients have been elusive. Between 2005 and 2012, we analyzed 191 HSCT in adult patients with leukemia with reduced-intensity conditioning (RIC) regimen (n = 79) and with myeloablative conditioning (MAC) regimen (n = 112). The direct medical costs were calculated from healthcare claims obtained from the Seoul National University Hospital, and the direct non-medical and the indirect costs were calculated from national statistics. The mean direct medical cost was $55,039, direct non-medical cost was $6394, and indirect cost was $7503 from transplantation to one yr after transplantation in the RIC group and $72,916, $6993, and $9057 in the MAC group, respectively, based on the exchange rate of Korean won 1060 = US$1. The total costs for one yr were $68,938 and $88,967, constituting for 273% and 357% of the per capita income, respectively. The total costs, direct medical costs, and indirect costs showed statistically significant differences (p = 0.006, p = 0.007, and p = 0.017). No significant differences were found for leukemia-free survival and overall survival. RIC-HSCT provides lower costs within the first year of transplantation with comparable long-term clinical outcomes.

IgG Hypogammaglobulinemia One Year After Heart Transplantation: A Persistent Risk Factor for Severe Infection.

Objective. We have previously described that IgG hypogammaglobulinemia (HGG: IgG<600 mg/dL) during the first month after transplantation is a risk factor for severe infection during the first year after heart transplantation. Our group remains concerned, however, about the persistence of this problem in a subgroup of patients long-term after transplantation and regarding its potential impact on infection risk. Hypothesis: HGG is a risk factor of severe infection long-term after transplantation. Objective: To characterize the prevalence of HGG and its impact on the prevalence of severe infections in heart recipients after the first year of transplantation. Methods. Design. Retrospective study. 122 heart recipients. IgG monitoring was performed at month 12 after transplantation by nephelometry. Clinical follow-up from one-year after transplantation to development of infection or latest visit: 24-111 months. Clinical outcomes: Severe infection defined as all infections that required antimicrobial therapy in hospital after the first year of transplantation. Statistics: Logistic regression. Results. The prevalence of HGG after transplantation was as follows: day 7 (35.4%), day 30 (50%), day 90 (33%), day 180 (23.7%), 1 year (18%). During the follow-up period after the first year of transplantation, 26 patients (21.3%) developed at least one episode of severe infection. Distribution of infection: Bacterial meningitis (n=1), bacterial pneumonia (n=10), other bacterial infections (n=6), CMV disease (n=5), other viral infection (n=1), systemic aspergillosis (n=1), intestinal strongyloidiasis (n=1), severe influenza A (n=1). HGG at month 12 was a risk factor of severe infection (Odds-ratio [OR] 24, p<0.001) and of deadly infections (OR 9.5, p=0.0037). Clinical variables that were associated with infection risk were: receptor negative for CMV serology and patients who had CMV or bacterial infections during the first year. In multivariate logistic regression analysis long-term HGG was an independent predictor of infection (OR 21, p<0.001) after adjustment by clinical variables. Conclusion: HGG at one year of heart transplantation is a risk factor of infection. IgG monitoring must be performed up to the first year after transplantation.

Use of Granulocyte Colony-Stimulating Factor and the Incidence of Rejection in Kidney Transplantation.

Background: Kidney transplant (KT) recipients are at risk for developing neutropenia due to a wide range of post-transplant medications. There is controversy about the use of granulocyte colony stimulating factors (G-CSF) in SOTR as several small studies have suggested a link between use and rejection. The objective of this study is to identify the risk of acute cellular rejection in KT recipients who received ≥1 dose of G-CSF within the first year of transplant. Methods: Following IRB approval, a retrospective chart review was conducted on adult patients who underwent KT between 1/1/06 and 12/31/12. Only patients who received alemtuzumab and had documented biopsy results within the study period were included. Maintenance IS was protocol driven for all patients and generally included MMF and tacrolimus. The first episode of biopsy-proven rejection within 180 days of G-CSF administration or within 1 year post-transplant if no G-CSF was given were recorded. Rejection was classified by Banff 07 criteria. Results: 404 patients were included. 91 (22.5%) patients received ≥1 dose of G-CSF within the first year post-transplant. Demographics were similar between groups (Table 1). Rejection was more likely to occur (OR = 1.68, p=0.031) and be more severe (OR 2.26, p=0.007) in G-CSF patients than the control group (Table 2).Table: No Caption available.Table: No Caption available.Conclusion: The odds of rejection were higher in patients who received ≥1 dose of G-CSF within the first year of transplant. Patients were more likely to have moderate to severe rejection compared to mild or no rejection if they received G-CSF. An ongoing analysis is underway to identify other potential contributing factors for rejection.

A Prospective Randomized Trial Aimed to Reduce the Incidence of Cytomegalovirus (CMV) Infection in Kidney Transplant Recipients.

Introduction: CMV infection is associated with inferior long-term patient and graft survival. This single center prospective randomized study compares the influence of 3 immunosuppressive regimens on the incidence of CMV infection in kidney transplant recipients. Methods: This is a single center prospective randomized study included 288 low immunological risk kidney transplant recipients to receive: (G1, N=85) single 3 mg/kg dose of antithymocyte globulin, reduced exposure tacrolimus (TAC<5 ng/ml), everolimus (EVR: 4-8 ng/mL) and prednisone; (G2, N=102) basiliximab, reduced exposure TAC (6 ng/ml for 3 months then <5 ng/mL thereafter), EVR (4-8 ng/mL) and prednisone; (G3, N=101) basiliximab, TAC (6-8 ng/ml), mycophenolate (MPA) and prednisone. None of the patients received any CMV prophylaxis. CMV viral replication was monitored weekly using pp65 antigenemia and PCR. The primary outcome is the incidence of CMV infection (viremia or disease) during the first year of transplantation. This report includes data of all patients up to 6 month after transplantation. Results: There were no differences in demographic characteristics including pre-transplant CMV donor/recipient serostatus. The incidence of first CMV infection episode was lower in EVR groups (4.7 vs. 7.8 vs. 35.6%, p<0.0001). There was no difference comparing mean time to first CMV infection episode or mean time of ganciclovir treatment. The total number of CMV infection episodes was also lower in EVR groups (4 vs. 14 vs. 55) because there were no recurrent episodes in G1 but 6 in G2 and 19 in G3. Twelve patients were converted from MPA to EVR due to CMV infection. There were no differences in incidence of biopsy proven acute rejection (8 vs. 20 vs. 14%, p=0.085), wound-healing adverse events (28 vs. 35 vs. 25%, p=0.2), delayed graft function (48 vs. 53 vs. 45%, p=0.4), mean estimated GFR (64±24 vs. 58±23 vs. 66±29 ml/min, p=0.06) and mean protein/creatinine ratio (0.5±1.0 vs. 0.4±0.7 vs. 0.3±0.9, p=0.5). There were 8 deaths (G1=2; G2=3; G3=3) and 6 graft losses (G1=0; G2=3; G3=3). Conclusions: This 6 month analysis indicates that patients receiving EVR are at lower risk of developing CMV infection compared to patients receiving MPA. Patients receiving EVR showed efficacy and safety profiles comparable to those receiving MPA. DISCLOSURES:Tedesco, H.: Grant/Research Support, Novartis.

The Association of Pretransplant HeartMate II Left Ventricular Assist Device Placement and Heart Transplantation Mortality

Previous United Network for Organ Sharing (UNOS) analysis has shown an increase in posttransplant mortality with pretransplant pulsatile-flow left ventricular assist device (LVAD). Recent studies evaluating continuous-flow LVAD demonstrated improved durability, excellent survival, and improved quality of life. This study investigates the association of preheart transplant continuous-flow LVAD placement and posttransplant mortality using the UNOS database. Heart transplant patients listed after April 2004 (N = 48,090) during the era of HeartMate (HM) II LVAD usage were investigated. Patients with UNOS 1A and 1B status with (n = 1,435) and without HMII (n = 16,379) placement before the heart transplantation were evaluated. Preliminary descriptive statistics suggested an extensive heterogeneity in patient characteristics between HMII LVAD recipients and nonrecipients. Propensity scores (1:2) were used to match HMII LVAD recipients and nonrecipients characteristics and donor characteristics. This resulted in a final sample of 2,265 patients (758 with HMII pretransplant placement and 1,507 without HMII pretransplant placement). The Kaplan-Meier curves were evaluated for the differences in postheart transplant mortality in patients with and without HMII pretransplant placement. A time-dependent Cox regression model was used to study the hazard ratios (HRs) for the association between HMII pretransplant placement and posttransplant survival. The mean age of the study group was 51.9 years old (standard deviation: 12.3). HeartMate II pretransplant placement was associated with no statistically significant difference in the risk of 30 days (HR = 1.23, 95% confidence interval [CI]: 0.79-1.95, p = 0.36) and 1 year posttransplant mortality (HR = 1.31, 95% CI: 0.85-2.01, p = 0.22) compared with non-HMII recipients. The use of HMII LVAD before heart transplantation, however, was associated with a statistically significant 64% lower risk (HR = 0.36, 95% CI: 0.16-0.77, p = 0.01) of mortality among heart transplant patients who survived beyond the first year of transplantation. Continuous-flow LVAD pretransplant placement is associated with improved long-term (>1 year) survival after heart transplantation.

Different Classifications Yield Variance in Metabolic Syndrome Prevalence and Dynamics in Renal Transplant Recipients

IntroductionThe metabolic syndrome (MS) is a combination of factors that are associated with increased cardiovascular diseases. High MS prevalence was reported in renal transplant recipients. However, little is known about the longitudinal prevalence and its dynamic properties in this population. We studied the longitudinal prevalence of MS at 3 and 12 months post-transplantation using 3 classifications. Patients and MethodsWe studied a cohort of 322 patients who underwent transplantation between 1996 and 2003 who had isotopic measurement of transplant glomerular filtration rate and MS assessment at 3 and 12 months after transplantation. Prevalence and change of MS status in terms of acquisition or regression were analyzed based on World Health Organization (WHO), International Diabetic Federation (IDF), and The Adult Treatment Panel-III (ATP-III) classifications. ResultsThe prevalences at 3 and 12 months were as follows: WHO, 8.4% and 8.1%; IDF, 25.8% and 29.8%; and ATP-III, 34.3% and 36.6%, respectively. Change in MS status was noted in 9.7%, 16.4%, and 20.5% of subjects within WHO, IDF, and the ATP-III classifications, respectively. Prevalence was significantly lower with WHO than IDF and ATP-III. Prevalence was the highest with ATP-III. However, the difference with IDF was significant only at 3 months post-transplantation. Depending on the classification used, 10%–21% of subjects change MS status within the first year of transplantation. ConclusionLongitudinal analysis confirms the high prevalence of MS and also highlights the dynamics of MS. We think both prevalence and dynamics should be accounted for when studying outcomes.

Long‐term experience of steroid‐free pediatric renal transplantation: Effects on graft function, body mass index, and longitudinal growth

Increased focus on the potential negative side effects of steroid usage in pediatric transplantation has led to steroid minimization or steroid-free transplantation. In this study, we report results after complete steroid avoidance in renal transplantation in the period 1994-2009. We evaluate the effects of complete steroid avoidance on allograft function, BMI, and linear growth. The majority of transplanted children were induced with antithymocyte globulin and immunosuppressed with a calcineurin inhibitor and mycophenolate mofetil. Steroids were given only when rejection occurred or due to comorbidities. Anthropometric data were collected from 65 transplantations in 60 children. Patient survival was 93%; graft survival was 81% after five yr (N = 42) and 63% after 10 yr (N = 16). Acute rejection within the first year of transplantation was 9%. The distribution of the children's BMI before transplantation was normal; the mean BMI-SDS was 0.21 before transplantation, and this value remained stable during the next five yr. Post-transplantation the children demonstrated significant improved growth as the mean height-SDS increased significantly from -1.7 to -1.1. Catch-up growth was most pronounced in the youngest (< six yr). Steroid-free immunosuppression in pediatric renal transplantation is safe and protects against steroid-induced obesity and short stature.

Acute Cholecystitis Occurs More Commonly Than Expected Following Allogeneic Hematopoietic Stem Cell Transplantation and Is Ineffectively Diagnosed Using Abdominal Ultrasound

BackgroundHaving observed an unexpectedly high rate of acute cholecystitis following allogeneic hematopoietic stem cell transplantation (allo-HCT), we sought to define the risk factors for development of acute cholecystitis following allo-HCT, as well as the incidence, radiographic presentation, and outcomes of this disease in the transplant population. MethodsBetween January 2001 and December 2011, 644 patients underwent allo-HCT at our institution. Using ICD-9 codes, we screened this population for a diagnosis of acute cholecystitis or for cholecystectomy in the first year following HCT. Cases were confirmed through manual chart review, and were defined as having one or more imaging modalities positive for acute cholecystitis or having surgical gallbladder pathology consistent with acute cholecystitis. We then conducted a nested case-control study with controls randomly selected through incidence density sampling of the transplant cohort at a rate of 3:1, matching for age and sex. Using logistic regression, we evaluated multiple potential risk factors for the development of acute cholecystitis, including underlying hematologic malignancy, graft-versus-host-disease (GVHD), total parenteral nutrition (TPN) use, graft source, ABO incompatibility, >10% weight loss, conditioning regimen, and cytomegalovirus reactivation. Finally, we conducted a separate case-control study to evaluate the effectiveness of multiple radiographic studies in the diagnosis of acute cholecystitis in HCT recipients (n=32) compared to randomly selected non-transplant control patients who were diagnosed with acute cholecystitis at our institution (n=96). ResultsThe incidence of acute cholecystitis in the first year of transplant was 5.0% (32/644 patients). Of the 32 patients, 21 (65.6%) were male and 11 (34.4%) were female with a median age of 52.2 years (range, 24–75 years). Median time from HCT to diagnosis of acute cholecystitis was 56.5 days (range, 6–342 days). Twenty of 32 patients (62.5%) were treated with cholecystectomy, 7 (21.9%) with percutaneous cholecystostomy drainage, and the remaining 5 (15.6%) with conservative medical management. Twenty of the 32 patients who developed acute cholecystitis died within one year of HCT (62.5%), compared with 19 of 96 control patients (19.8%), (p<0.001). Of the 20 cholecystitis patients who died, three (15%) died as a direct result of acute cholecystitis; cause of death was septic shock in all 3 cases. HCT patients who received TPN had a higher risk of developing acute cholecystitis (multivariate OR, 3.41; p=0.009), while development of GVHD was protective against developing acute cholecystitis (multivariate OR, 0.28; p=0.006). When accounting only for development of grade III-IV GVHD, a trend towards protection remained but was not statistically significant (OR, 0.24; p=0.061). Ultrasound findings were equivocal for acute cholecystitis (vs. definitively positive or negative) more frequently in allo-HCT patients than in non-HCT patients (50.0% vs. 30.6%), although this difference was not statistically significant (p=0.063). Of the 32 case patients, 30 (93.8%) had US performed, and of these only 13 (43.3%) had an US positive for acute cholecystitis. Computed tomography (CT) scan was equivocal (versus definitively positive or negative) for acute cholecystitis at similar rates in allo-HCT and non-HCT patients (54.7%, vs. 41.2%, p=0.331), and cholescintigraphy (HIDA) scan was positive for cholecystitis at similar rates in both populations (80.0% vs. 77.4%, p=0.82). ConclusionsAcute cholecystitis is a common complication of allo-HCT, especially in patients who received TPN. It is associated with a high 1-year mortality rate, and abdominal US has suboptimal performance in diagnosing it. Our data suggest that a high index of suspicion and use of alternative imaging modalities are required to make a prompt diagnosis and may improve the outcomes of allo-HCT patients. Disclosures:No relevant conflicts of interest to declare.

Pathologic and Clinical Features Of CD30+ Post-Transplant Lymphoproliferative Disorders: A Large Retrospective Single Institutional Study

IntroductionB-cell post-transplant lymphoproliferative disorders (B-PTLD) represent a spectrum of lymphoid neoplasms arising as a consequence of impaired T-cell surveillance secondary to immunosuppressive medications. Epstein-Barr Virus (EBV) has been implicated in the development of B-PTLD. B-PTLDs diagnosed within one year post-transplant are more likely to be associated with EBV whereas B-PTLD diagnosed after a year are more likely to be EBV-negative and are associated with worse prognosis. Studies have shown that EBV up-regulates CD30 expression, a member of the TNF-receptor superfamily (Haque et al 2011). Novel agents are now available that target cells expressing CD30. Hence, knowledge of the expression profiles and the clinical characteristics of CD30+ neoplasms is warranted. In this study, we evaluated CD30 expression in 59 cases of B-PTLD and correlated CD30 and EBV status with clinical characteristics. MethodsConsecutive cases of B-PTLD diagnosed between 1997 and 2013 were retrieved from our archives. Immunohistochemistry (ISH) for CD30 was performed on formalin-fixed, paraffin embedded biopsies using the BerH2 monoclonal antibody (BioSB, Santa Barbara, CA) according to standard methods. Positive expression was pre-defined as CD30 expression by ≥20% of the lesional cells (Figure 1). Log-rank and Fischer's Exact 2-sided Test were performed in STATA 11, as appropriate. ResultsThe 59 B-PTLDs occurred in 54 patients. Three patients had two different sites biopsied during the diagnostic workup. Two other patients had recurrent B-PTLD. The median age at diagnosis was 22.8 years old (range 1.2 to 75.9 years); 65% were male. The median time from transplant to diagnosis was 2.6 years (range 6 weeks to 15.9 years, mean 4.2 years). Eighteen cases (35%) were diagnosed within the first year of transplantation. The organs transplanted are detailed in Table 1 with the percentage of CD30+ cases noted. Prior to transplantation, only 25/44 (57%) patients were EBV IgG seropositive, likely reflecting the number of children who were younger than age ten when transplanted (21/52; 40%). (Orjuela et al 2011). Serum EBV Polymerase Chain Reaction (PCR) was positive in 18/27 (67%) cases analyzed.Table 1Organ TransplantednPercentage CD30+Kidney1560%Heart2263%Lung3100%Heart-Lung1100%Liver1060%Pancreas10%Small Bowel1100%Bone Marrow1100%Pathological data are summarized in Table 2. In total, 39 of 59 cases (66%) showed 20% or more CD30 expression. Positive EBV ISH was significantly associated with CD30 expression (r=0.38, p< 0.01). Of 59 tumors informative for CD30 and EBV (by ISH), 32/41 of EBV-positive tumors were CD30 positive (78%) while 7 of 18 tumors that were EBV negative were CD30 positive (39%) (r=0.38 for the association of EBV and CD30 status, p=0.01). Detectable serum viremia was associated with CD30 status (r=0.49, p=0.02). There was no association found between CD20 status and CD30 status. There was no significant association between CD30 status and ki67 index or c-myc expression either (data not shown).Table 2HistologyCD 30 PositiveCD 20 PositiveEBER PositivePolymorphic (n=25)22/ 25 = 88%19/25= 76%22/25 = 88%Monomorphic: DLBCL (n=23)12/23 = 52%19/23 = 83%14/23 = 61%Monomorphic: Burkitt Lymphoma (n=3)1/3 = 33%3/3 = 100%1/3 = 33%Monomorphic:Plasmacytoma-like(n=8)4/8 = 50%4/8 = 50%4/8 = 50% ConclusionWe observed a high frequency of CD30 expression in patients with B-PTLD. Expression of CD30 correlates with ISH evidence of EBV infection in B-PTLD. In addition, positive serum EBV PCR was associated with CD30 expression. These two findings further support the link between EBV infection and CD30 expression. CD30 positivity was still found in 39% of EBER – negative cases, suggesting that CD30 ISH should be considered on all cases of B-PTLD. A monoclonal antibody conjugated to the cytotoxic agent MMAE,Brentuximab Vedotin (SGN-35), has shown activity in clinical trials against CD30 positive lymphomas (Jacobson et al 2012). Considering the relatively common prevalence of CD30+ expression in PTLD, brentuximab vedotin could be considered for study in combination with traditional front-line therapies or as an alternative therapy for relapsed/refractory disease. A prospective clinical trial (NCT 01805037) at Northwestern University is ongoing. Disclosures:Schecter:Seattle Genetics: Research Funding, Speakers Bureau. O'Connor:Seattle Genetics: Research Funding.

Broncho-Bronchiolitis Obliterans After Living-Donor Lung Transplantation

Broncho-Bronchiolitis Obliterans After Living-Donor Lung Transplantation