Acute Cellular Rejection Episodes Research Articles

Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.

Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development.

Intestine Transplantation Across a Positive Crossmatch With Preformed Donor-Specific Antibodies

BackgroundWe describe our experience using a modified protocol for immunosuppression for intestine transplantation across a positive crossmatch. Patients who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events with comparison to procedure-matched controls on our standard protocol of immunosuppression. Patients and MethodsWe used a modified protocol for intestine and multivisceral transplantation for patients with a positive flow crossmatch. In addition to our standard protocol, patients with positive crossmatch were given rituximab and intravenous immunoglobulin (IVIg) preoperatively. DSA was sent for clinical evaluation at monthly intervals. Patients were screened for rejection by endoscopic evaluation. ResultsFour patients underwent transplantation within a single year across a positive crossmatch. Two received isolated intestine transplants and 2 had multivisceral transplantation (MVT). During the 12-month follow-up, 1 patients had an episode of severe acute cellular rejection, which was managed with increased immunosuppression. None of the patients had episodes of cytomegalovirus infection. One patient developed major infection and 3 patients developed minor bacterial infections. Among procedure-matched controls with negative final crossmatch on standard management (no preoperative rituximab or IVIg), 2 developed mild acute cellular rejection and 2 developed minor infections. One developed cytomegalovirus viremia with invasion to the colonic mucosa. ConclusionsWe report our protocol for immunosuppression for IT and MVT across a positive crossmatch. This allowed transplantation despite the presence of a positive crossmatch, with low rejection rates but potentially increased risk for major infections compared to the negative crossmatch controls on our standard protocol.

A Case Report of Acute Cellular Rejection Following Intestinal Transplantation Managed With Adalimumab

There is a higher incidence of acute cellular rejection (ACR) in small bowel transplantation (SBT) compared with transplantation of other solid organs. Although there are reports on the use of infliximab to successfully treat ACR refractory to other treatments, there are no reports, to our knowledge, regarding the use of adalimumab. We present a case of a female patient with a history of Crohn's disease who underwent an isolated SBT and developed an episode of severe ACR. She was initially treated with methylprednisolone, thymoglobulin, basiliximab, and a dosage adjustment of tacrolimus. Results of repeat endoscopies and biopsies revealed no significant improvement. The patient initiated treatment with adalimumab every 2 weeks for a total of 6 months, in addition to maintenance treatment with prednisone and tacrolimus. Subsequent evaluations showed gradual improvement to normal mucosa and villi without ulceration. A regimen that incorporates adalimumab can thus be used to treat ACR after intestinal transplantation. Larger multicenter studies are needed to show the full efficacy of this therapeutic regimen.

Long-Term Outcomes of Intestinal and Multivisceral Transplantation at a Single Center in Argentina

BackgroundIntestinal failure (IF) patients received parenteral nutrition (PN) as the only available therapy until intestinal transplantation (ITx) evolved as an accepted treatment. The aim of this article is to report the long-term outcomes of a series of ITx performed in pediatric and adult patients at a single center 9 years after its creation. Patients and MethodsThis is a retrospective analysis of the ITx performed between May 2006 and January 2015. Diagnoses, pre-ITx mean time on PN, indications for ITx, time on the waiting list for types of ITx, mean total ischemia time, and warm ischemia time, time until PN discontinuation, incidence of acute and chronic rejection, and 5-year actuarial patient survival are reported. ResultsA total of 42 patients received ITx; 80% had short gut syndrome (SG); the mean time on PN was 1620 days. The main indication for ITx was lack of central venous access followed by intestinal failure–associated liver disease (IFALD) and catheter-related infectious complications. The mean time on the waiting list was 188 days (standard deviation, ±183 days). ITx were performed in 26 children and 14 adults. In all, 32 procedures were isolated ITx (IITX); 10 were multiorgan Tx (MOT; 3 combined, 7 multivisceral Tx (MVTx), 1 modified MVTx and 2 with kidney); 2 (4.7 %) were retransplantations: 1 IITx, 1 MVTx, and 5 including the right colon. Thirteen patients (31%) received abdominal rectus fascia. All procedures were performed by the same surgical team. Total ischemia time was 7:53 ± 2:04 hours, and warm ischemia time was 40.2 ± 10.5 minutes. The mean length of implanted intestine was 325 ± 63 cm. Bishop–Koop ileostomy was performed in 67% of cases. In all, 16 of 42 Tx required early reoperations. The overall mean follow-up time was 41 ± 35.6 months. The mean time to PN discontinuation after Tx was 68 days (P = .001). The total number of acute cellular rejection (ACR) episodes until the last follow-up was 83; the total number of grafts lost due to ACR was 4; and the total graft lost due to chronic rejection was 3. At the time of writing, the overall 5-year patient survival is 55% (65% for IITx vs 22% for MOT; P = .0001); 60% for pediatric recipients vs 47% for adults (P = NS); 64% when the indication for ITx was SG vs 25% for non-SG (P = .002). ConclusionsAt this center, candidates with SG, in the absence of IFALD requiring IITx, showed the best long-term outcomes, independent of recipient age. A multidisciplinary approach is mandatory for the care of intestinal failure patients, to sustain a rehabilitation and transplantation program over time.

Biopsy-proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal.

Biopsy-proven acute cellular rejection (ACR) is the primary efficacy endpoint in most randomized trials evaluating immunosuppression in liver transplantation. However, ACR is not a major cause of graft loss, and a certain grade of immune activation may be even beneficial for long-term graft acceptance. Validated criteria to select candidates for liver biopsy are lacking, and routine clinical practice relies on liver tests, which are inaccurate markers of ACR. Indeed, both the agreement among clinicians to select candidates for liver biopsy and the correlation between the clinical suspicion of ACR and histological findings are poor. In randomized trials evaluating immunosuppression protocols, this concern grows exponentially due to the open-label and multicenter nature of most studies. Therefore, biopsy-proven ACR is a suboptimal efficacy endpoint given its limited impact on prognosis and the heterogeneous diagnosis, which may increase the risk of bias. Chronic rejection and/or graft loss would be more appropriate endpoints, but would certainly require larger studies with prolonged surveillances. An objective method to select candidates for liver biopsy is therefore urgently needed, and only severe episodes of histological ACR should be considered as potentially harmful. Emerging surrogate markers of ACR and antibody-mediated rejection require further investigation to determine their clinical role.

Acute Cellular Rejection and C4d Positivity in Heart Transplantation : A Manifestation of Asymptomatic Antibody-Mediated Rejection?

The role of routine C4d staining in endomyocardial biopsy specimens is uncertain. The implications of a diagnosis of acute cellular rejection (ACR) with a positive C4d with or without any evidence of antibody-mediated rejection (AMR) are unclear. This study sought to evaluate a distinct phenotype of ACR+/C4d+ in AMR- patients. Data on C4d, ACR, and AMR were collected. Donor-specific antibody (DSA), panel-reactive antibody (PRA), flow crossmatch, and data on ACR and AMR episodes were also reviewed. Thirty-five patients were followed. Group I with C4d+ biopsy specimens was compared with group II with C4d- biopsy specimens. ACR greater than 1R was higher in group I compared with group II (50% vs 7.4%; P = .01). Clinical suspicion of AMR, positive retrospective crossmatches, and detection of de novo DSA were also higher in group I. Our result indicate that C4d and ACR positivity in posttransplant patients may be a harbinger of a subclinical form of asymptomatic AMR.

Effects of induction therapy with alemtuzumab versus antithymocyte globulin among highly sensitized kidney transplant candidates.

We retrospectively compared induction therapy utilizing alemtuzumab and antithymoglobulin (ATG) in high-risk kidney transplant recipients in our center. Two hundred and fifty-one patients underwent kidney transplantation between 2009 and 2012. The high-risk patients were defined as those who had two or more times kidney transplantation and/or more than 30% panel reactive antibody. We studied 130 high-risk kidney transplant candidate; 58 (44.6%) patients received induction immunosuppressive therapy with alemtuzumab, and 72 (55.4%) with ATG. Delayed graft function developed in 11 patients receiving alemtuzumab, against the 27 patients who receiving ATG (P = 0.021). Acute cellular rejection episodes were observed in five patients in the alemtuzumab group and 19 patients in the ATG group (P = 0.009). There were three graft failures in the alemtuzumab group and eight graft failures in the ATG group due to rejection episodes. We found immunosuppressive induction therapy with alemtuzumab a significantly less incidence of acute rejection and delayed graft function than induction therapy with ATG in the high-risk kidney transplant recipients.

Alloreactive T Cells to Identify Risk HLA Alleles for Retransplantation After Acute Accelerated Steroid-Resistant Rejection

The risk of rejection by cellular alloreactivity to the transplant donor is not routinely assessed. Here we analyzed alloreactive T cells in kidney transplant recipients and report how their detection may have helped to prevent rejection of a second kidney graft in a patient with a history of acute accelerated steroid-resistant nonhumoral rejection. Alloreactive CD4 and CD8 T cells were quantified using a flow-cytometric mixed lymphocyte reaction assay based on interferon-γ induction. A group of 16 nonrejecting transplant recipients did not show any alloreactive T-cell immunity to their respective donors, whereas alloreactivity to third-party controls was detectable. In the patient with rejection, HLA-specific antibodies were not detectable before and shortly after rejection, but after transplantation the patient showed exceptionally high frequencies of alloreactive T cells against 2 of 11 HLA-typed controls (0.604% and 0.791% alloreactive CD4 T cells and 0.792% and 0.978% alloreactive CD8 T cells) who shared HLA alleles (HLA-A*24, -B*44, -C*02, -DQB1*5) with the kidney donor. These HLA alleles were subsequently excluded for allocation of a second graft. No alloreactive T cells were observed toward the second kidney donor, and this transplantation was performed successfully. Thus, shared HLA alleles between the donor and third-party controls may suggest that alloreactive T cells had contributed to rejection of the first graft. The rejecting patient highlights that determination of cellular alloreactivity before transplantation may be applied to identify unacceptable mismatches and to reduce the risk for acute cellular rejection episodes.

Disease Recurrence and Acute Cellular Rejection Episodes During the First Year After Lung Transplantation Among Patients With Sarcoidosis.

Sarcoidosis is reported to recur after lung transplantation (LT). We sought to determine the frequency of recurrent disease after LT and predictors of recurrence. We also evaluated the incidence and severity of acute cellular rejection (ACR) episodes among these patients. The database of LT patients at Cleveland Clinic was interrogated for sarcoidosis patients who underwent LT between May 1993 and 2011. Charts were reviewed for demographics, type of transplant, posttransplant biopsy findings, and outcomes. Data were available for 30 patients (mean age, 50 ± 9.3 years; range, 30-65 years; M-to-F ratio, 17:13; single-to-double-to-heart lung ratio, 5:24:1). Recurrence of sarcoidosis was noted among 7 patients (pathological recurrence in all and radiological findings suggesting recurrence in 1 patient) with no impact on overall outcomes. Presence of granulomas on explanted lungs was the only predictor of recurrence (85.7% vs 30.4%, odds ratio, 13.7; 1.4-136.2; P = 0.02).Overall burden of ACR episodes on all bronchoscopies was significantly lower in patients with disease recurrence (7.6 % vs 21.3% of biopsies, P = 0.038). Among patients with recurrent disease, ACR did not develop once disease recurrence had been seen on transbronchial biopsy. A significant proportion of sarcoidosis patients have disease recurrence after LT and presence of active granulomas on explant is associated with subsequent recurrence. There may be an association of recurrence with lower frequency of ACR episodes. There does not appear to be any impact of sarcoidosis recurrence on 1-, 3-, or 5-year survivals.

Hepatobiliary Quiz (Answers)—15 (2015)

Hepatobiliary Quiz (Answers)—15 (2015)

Serial changes in longitudinal graft function and implications of acute cellular graft rejections during the first year after heart transplantation.

The aim of this prospective study was to use left ventricular global longitudinal strain (LV-GLS) as a non-invasive tool for the monitoring of graft function in relation to acute cellular rejection (ACR) during the first year after heart transplantation (HTX). The study population consisted of 36 patients undergoing HTX from November 2010 until October 2013. Patients were followed by comprehensive echocardiography and biopsies at 2 weeks and 1, 3, 6, and 12 months after HTX. ACRs were classified based on the ISHLT classification (0R-3R). Patients were divided into two groups according to the presence of one or more episodes of biopsy proven ≥grade 2R ACR during follow-up. We found that LV-GLS and tricuspid annular plane systolic excursion (TAPSE) were significantly related to ACR burden in a linear regression model. The absolute difference in LV-GLS between patients in the ACR group (-14.4%) and patients in the ACR-free group (-16.8%) was -2.4% (P < 0.01) 12 months after HTX. In the ACR group, patients' LV-GLS did not improve between 1 and 12 months, whereas an improvement of -2.9% was seen in the ACR-free group in this period (P < 0.01). The two groups appeared not to differ in terms of diastolic Doppler parameters or LV ejection fraction, but TAPSE was 15.3 ± 2.8 mm in the ACR-free group vs. 13.2 ± 2.1 mm ACR group, P < 0.05, 12 months after HTX. Gradual improvement of longitudinal LV and RV function was seen within the first year after HTX, but the degree of recovery was strongly influenced by ACR episodes.

PTH-134 Reduced calcineurin inhibitor exposure early after liver transplantation protects against renal dysfunction independently of the use of basiliximab induction therapy

Introduction Basiliximab use with delayed entry of Tacrolimus (TAC) as renal sparing agent may help reduce renal impairment in liver transplant (LT) recipients. We aimed to evaluate factors affecting renal dysfunction and the effect of basiliximab post-LT. Method All consecutive LT patients (1/2006–1/2014) with a follow up >3months and eGFR 2 at day 1 post-LT were analysed for factors known to affect renal dysfunction: biochemical/clinical data, donor age, cold/warm ischemia time, mean trough TAC levels up to days 7, 15, 30 post-LT, basiliximab use, initial/maintenance immunosuppression, acute cellular rejection (ACR), diabetes mellitus (DM) pre and post-LT, systemic hypertension, days on filtration post-LT. Renal impairment was defined as mild: eGFR 60–89 and moderate/severe: eGFR Results 126 patients given basiliximab were compared with 189 consecutive patients with eGFR 5 ng/ml vs 41%(38/92) with TAC Logistic regression analysis showed that factors associated with moderate-severe renal impairment (eGFR 50years (p 5 ng/ml at week 1 post-LT(p = 0.003, OR=0.4, 95% CI=0.3–0.7) and mean CNI levels >7 ng/ml up to 15 days post-LT(p = 0.019 OR=0.85, 95% CI=0.75–0.97). The same factors were associated with mild renal impairment (eGFR 7 ng/ml at days 15 post-LT (p = 0.003 OR=1,9 95% CI=1.2–2.9) and use of steroids >3months post-LT(p = 0.006, OR=0.7, 95% CI=0.5–0.9). Conclusion Basiliximab use allows reduced TAC trough levels with less episodes of ACR compared with the control group. However, TAC trough levels Disclosure of interest None Declared.

A Single-Center Retrospective Clinicopathologic Study of Endomyocardial Biopsies After Heart Transplant at Baskent University Hospital in Ankara, 1993-2014

The purpose of this study was to investigate the frequency and prognostic importance of acute cellular rejection after heart transplant. All 84 heart transplant patients at our center from January 1993 to January 2014, including all 576 endomyocardial biopsies, were evaluated with retrospective review of clinical records and endomyocardial biopsies. Routine and clinically indicated endomyocardial biopsies after heart transplant were graded for acute cellular rejection (2005 International Society for Heart and Lung Transplantation Working Formulation). Survival analysis was performed using Kaplan-Meier method. There were 61 male (73%) and 23 female recipients. Median age at heart transplant was 29 years (range, 1-62 y). Posttransplant early mortality rate was 17.9% (15 patients). In the other 69 patients, 23 patients died and 46 patients (66.7%) were alive at mean 69.3 ± 7.2 months after heart transplant. Mean follow-up was 35.4 ± 29.8 months (range, 0.07-117.5 mo). Mean 8.4 ± 4.2 endomyocardial biopsies (range, 1-19 biopsies) were performed per patient. Median first biopsy time was 7 days (range, 1-78 d). The frequency of posttransplant acute cellular rejection was 63.8% (44 of 69 patients) by histopathology; 86% patients experienced the first episode of acute cellular rejection within 6 months after transplant. There were 18 patients with acute cellular rejection ≥ grade 2R on ≥ 1 endomyocardial biopsy in 44 patients with acute cellular rejection. No significant difference was observed between survival rates of patients with grade 1R or ≥ grade 2R acute cellular rejection, or between survival rates of patients with or without diagnosis of any grade of acute cellular rejection. Acute cellular rejection was not related to any prognostic risk factor. Acute cellular rejection had no negative effect on heart recipient long-term survival, but it was a frequent complication after heart transplant, especially within the first 6 months.

Eosinophil count, allergies, and rejection in pediatric heart transplant recipients

Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted.

Positive C4d in Kidney Transplantation Biopsy: Clinical Impact

BackgroundDeposition of C4d in peritubular capillaries of renal graft is normally associated with the presence of antibody-mediated rejection. The clinical impact of its presence in patients with renal transplant in Colombia is uncertain, as well as the association in acute rejection and the response to the management and survival of the graft. The aim of this study was to determine the risk of having positive C4d in biopsies of patients with episodes of acute cellular rejection. MethodsWe retrospectively reviewed 226 biopsies of kidney transplantation, all of them with acute rejection and histopathological findings classified according to Banff criteria 2009 and performed between January 2005 and December 2012 for graft dysfunction. C4d staining was performed by immunohistochemistry. ResultsC4d staining was positive in 25 of 226 biopsies. Rejection time in patients with positive C4d was 15 months in average vs 8 months with negative C4d. ConclusionsWith the use of a multivariate analysis, we found that the unique risk for C4d in our population was the positive panel reactive antibodies and elapsed time between transplant and the rejection (odds ratio: 2.12, P = .034) and that the other variables analyzed are not related to the expression of C4d.

Efficacy of ursodeoxycholic acid as an adjuvant treatment to prevent acute cellular rejection after liver transplantation: a meta-analysis of randomized controlled trials

Acute cellular rejection (ACR) after liver transplantation (LT) is one of the most common problems faced by transplant recipients in spite of advances in immunosuppressive therapy. Recently, clinical trials reported that ursodeoxycholic acid (UDCA) reduced the incidence of ACR significantly. However, others have shown contradictory conclusion. Therefore, we performed a meta-analysis of rigorous randomized controlled trials (RCTs) to determine the efficacy of UDCA in reducing ACR after LT. All RCTs that evaluated efficacy of UDCA as an adjuvant treatment to prevent ACR after LT were searched from PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect databases and Web of Science (from January 1981 to March 2012). There was no language limitation in these searches. Relevant abstracts of international meetings were also searched. References of each included study were searched manually. A total of 234 patients from four high-quality RCTs (Jadad score 4 to 5) were included in this meta-analysis. Prophylactic use of UDCA did not decrease the incidence of ACR (RR: 0.94, 95% CI: 0.77-1.16, P>0.05), steroid-resistant rejection (RR: 0.77, 95% CI: 0.47-1.27, P>0.05) and the number of patients with the multiple episodes of ACR (RR: 0.60, 95% CI: 0.28-1.30, P>0.05). Different intervention programs (high-dose vs low-dose UDCA; early vs delayed UDCA treatment) also did not alter the outcomes. UDCA, as an adjuvant treatment, was not able to prevent ACR and steroid-resistant rejection after LT. Further trials should be done to determine whether higher dose of UDCA will be beneficial.

Desensitization With Plasmapheresis and Anti-Cd20 for ABO Incompatible Kidney Transplantation From Living Donor: Experience of a Single Center in Italy

ObjectiveBlood group incompatibility in kidney transplants from a living donor can be successfully overcome by using various desensitization protocols: intravenous immunoglobulin, plasmapheresis (PP), immunoadsorption, and double filtration PP. Patients and MethodsFrom July 2010 to October 2013, we performed 10 ABO incompatible kidney transplantation (KT) procedures from a living donor. The desensitization protocol was based on rituximab and PP + cytomegalovirus immune globulin. All patients received induction with basiliximab, except 1 case treated with Thymoglobuline® (ATG) for the simultaneous presence of donor-specific antibody. Tacrolimus and mycophenolate mofetil were initiated at the time of desensitization and continued after the transplant. ResultsAfter a mean follow-up of 11.6 ± 10.4 months, all patients are alive with a functioning graft. The mean serum creatinine concentration at 1 month, 3 months, 6 months, and 1 year was 1.48 ± 0.29, 1.47 ± 0.18, 1.47 ± 0.27, and 1.5 ± 0.27 mg/dl. Three episodes of acute cellular rejection occurred in 2 patients. There was only 1 case of BK virus infection, treated with reduction of immunosuppressive therapy. The protocol biopsy specimens at 1, 3, and 6 months were C4d positive in the absence of acute rejection. ConclusionsDesensitization with rituximab, PP, and anti–cytomegalovirus immune globulin allowed us to perform transplants from living donors to ABO incompatible recipients with excellent results and reduced costs.

25-Hydroxyvitamin D Levels and Acute Cellular Rejection in Liver Transplant Patients

To investigate the association between 25-hydroxyvitamin D [25(OH)D] levels prior to liver transplantation (LT) and the development of acute cellular rejection (ACR) within the first year post LT. This retrospective study included 275 consecutive LTs performed in 262 patients at Mayo Clinic in Jacksonville, Florida over 13 months. A total of 149 patients met the inclusion criteria. The correlations between 25(OH)D levels and the development, severity, and number of biopsy-proven ACR episodes were assessed. The prevalence of 25(OH)D levels <30 ng/mL was 92%. No association was found between pre LT 25(OH)D levels and the diagnosis of ACR (P = .61). Mean ± SD pre LT 25(OH)D levels were 16.1 ± 6.8 ng/mL for 48 subjects with no rejection, 16.1 ± 8.2 ng/mL for those with a mild first episode of ACR (n = 58), and 18.4 ± 12.4 ng/mL for those who experienced a moderate/severe first ACR (n = 39). However, in a subgroup analysis of patients with 25(OH)D levels <30 ng/mL, there was a statistically significant negative correlation (P = .0252) between 25(OH) D level and the ACR rate. Vitamin D insufficiency and deficiency prior to LT was prevalent in our cohort. There was no statistically significant association between low 25(OH)D levels and the diagnosis or severity of ACR or the number of rejection episodes within the first year post LT. However, there was a negative correlation between 25(OH)D levels below 30 ng/mL and the rate of ACR within 1 year post LT.

Alemtuzumab in Lung Transplantation: An Open-Label, Randomized, Prospective Single Center Study

Induction therapy with alemtuzumab followed by lower maintenance immunosuppression (IS) has been associated with reduced morbidity and mortality in abdominal and heart transplantation (TX). In the current study, alemtuzumab, in combination with reduced levels of maintenance IS, was compared to thymoglobulin in combination with standard IS. Sixty consecutive patients who underwent lung transplantation (LUTX) at a single center were prospectively randomized in two groups: group A received alemtuzumab in conjunction with reduced doses of tacrolimus, steroids and mycophenolate mofetil. Group B received thymoglobulin in association with standard dose IS. Patient and graft survival, freedom from acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, kidney function, infectious complications and posttransplant lymphoproliferative disorder were analyzed. Alemtuzumab induction therapy resulted in complete the absence of ACR episodes ≥ A2 within the first year post-TX. The difference to thymoglobulin was significant (alemtuzumab 0 vs. ATG 0.33; p = 0.019). All other factors studied did not show any differences between the two groups. Alemtuzumab induction therapy after LUTX in combination with reduced maintenance IS significantly reduces higher-grade rejection rates. This novel therapeutic agent had no impact on survival, infections rates, kidney function and incidence of malignancies.

The natural history of lung function after lung transplantation for α(1)-antitrypsin deficiency.

Lung transplantation (LT) is an established treatment for end-stage lung diseases, including chronic obstructive pulmonary disease (COPD) associated with α1-antitrypsin deficiency (AATD). We sought to compare the post-transplantation course of patients with AATD and AAT-replete COPD. Between June 1991 and January 2008, a total of 231 patients with AAT-replete COPD and 45 with AATD underwent LT at Cleveland Clinic. Data reviewed included baseline recipient, donor, and surgical data; all spirometry evaluations; acute cellular rejection (ACR) events; and survival data. Endpoints included temporal change in FEV1, severity of ACR, and survival. A longitudinal temporal decomposition model was used for analysis. Comparison of overall rates of FEV1 decline in AATD and AAT-replete patients with COPD showed no significant differences (P > 0.09). However, although the single LT patients had similar trends in FEV1 in both groups, patients with AATD with double LT declined faster (P < 0.002) than the AAT-replete patients. No differences in the frequency or severity of ACR episodes were observed (P = 0.32). Furthermore, there was no difference in early or late mortality between patients with AATD and patients with AAT-replete COPD (P > 0.09). Although overall the post-LT FEV1 slope, severity of ACR, and survival among patients with AATD is similar to that of AAT-replete patients with COPD, patients with AATD with double LT have a faster rate of FEV1 decline. These findings support the eligibility of patients with AATD for LT, and suggest the need for additional studies to better understand the difference between single and double LT in AATD.