Treatment In Lung Transplant Recipients Research Articles

(693) - Clinical Utility of 1:16 Serum Dilution as a Predictor of Response to Therapeutic Plasma Exchange for HLA Antibody-Mediated Rejection Treatment in Lung Transplant Recipients: A Two Center Study

(693) - Clinical Utility of 1:16 Serum Dilution as a Predictor of Response to Therapeutic Plasma Exchange for HLA Antibody-Mediated Rejection Treatment in Lung Transplant Recipients: A Two Center Study

(1249) Impact of Neutropenia and Granulocyte Colony-Stimulating Factor Treatment in Lung Transplant Recipients

(1249) Impact of Neutropenia and Granulocyte Colony-Stimulating Factor Treatment in Lung Transplant Recipients

Carfilzomib versus rituximab for treatment of de novo donor-specific antibodies in lung transplant recipients

IntroductionDe novo donor-specific antibodies (DSAs) increase the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Both carfilzomib (CFZ) and rituximab (RTX) lower the mean fluorescent intensity (MFI) of DSAs, but comparative data are lacking. We compared CLAD-free survival and the degree and duration of DSA depletion after treatment of LTRs with CFZ or RTX. MethodsLTRs that received CFZ or RTX for DSA depletion between 08/01/2015 and 08/31/2020 were included. The primary outcome was CLAD-free survival. Secondary outcomes were change in MFI at corresponding loci within 6 months of treatment (ΔMFI), time to DSA rebound, and change in % predicted FEV1 6 months after treatment (ΔFEV1). ResultsForty-four LTRs were identified, 7 of whom had ≥2 drug events; therefore, 53 drug events were divided into 2 groups, CFZ (n = 17) and RTX (n = 36). Use of plasmapheresis, immunoglobulin, and mycophenolate augmentation was equivalent in both groups. CLAD-free survival with a single RTX event was superior to that after ≥2 drug events (p = 0.001) but comparable to that with a single CFZ event (p = 0.399). Both drugs significantly lowered the MFI at DQ locus, and the median ΔMFI was comparable. Compared to the RTX group, the CFZ group had a shorter median interval to DSA rebound (p = 0.015) and a lower ΔFEV1 at 6 months (p = 0.014). ConclusionAlthough both CFZ and RTX reduced the MFI of circulating DSAs, RTX prolonged the time to DSA rebound. Despite more pronounced improvement in FEV1 with RTX, comparable CLAD-free survival between the 2 groups suggests that both drugs offer a reasonable treatment strategy for DSAs in LTRs.

Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study.

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P=0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2 =0.9182) and patient survival (P=0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P=0.0074) and patient survival (P=0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

Rapid Detection of Airway Pathogens in Lung Transplant Recipients

Airway infections may necessitate prompt treatment in lung transplant recipients, given their immunosuppressed status, but maybe difficult to distinguish clinically from acute rejection, a potential antecedent of chronic lung allograft dysfunction and death. Traditional culture techniques can delay the time to diagnosis particularly for bacterial infections. We hypothesized that a rapid multiplex molecular assay could improve time to diagnosis and appropriate clinical decision making in lung transplant recipients. We performed a prospective observational clinical trial (NCT03933878) investigating the efficiency and accuracy of the BioFire Pneumonia Panel in the context of post-transplant bronchoscopy. This molecular assay tests the presence and/or quantity for 26 common airway bacterial and viral pathogens in under 2 hours. Prospectively enrolled lung transplant recipients had molecular and standard of care (SOC) diagnostics in parallel. Research clinicians performed shadow clinical decision making in real time using molecular diagnostic data in addition to clinical records. Time to report and interpretation were reported as median and interquartile ranges and compared by Wilcox rank-sum test. Agreement between methods, limited to pathogens on the molecular panel, was calculated by Gwet's AC1 statistic, which is robust despite skewed distributions. For the 148 enrolled subjects, molecular results were available at 3.8 [2.8-5.1] hours following bronchoscopy, which was 12.7 [6.3-30] hours prior to SOC viral results (P <0.001) and 1.8 [1.7-2.7] days prior to SOC bacterial culture results (P <0.001). Positive molecular results were interpreted 10.2 [7.9-23] hours following bronchoscopy, which was 2.4 [0.8-3.3] days less than SOC. Agreement between assays was 0.96 (95%CI 0.93-0.99) for bacteria and 0.92 (95% CI 0.86-0.97) for viruses. Of 24 positive molecular results, 5 resulted in a shadow antibiotic recommendation, whereas SOC results lead to antimicrobial initiation for 43. Notable molecular panel deficiencies included fungal pathogens and H. parainfluenzae, accounting for 17 and 13 of the 43 actionable SOC results, respectively. This molecular diagnostic could allow more rapid initiation of antibiotics in select cases and comparable viral detection versus SOC. However, as common lung transplant pathogens are not included in this panel, it cannot replace SOC microbial cultures.

P139 Dilution studies establish hla donor-specific antibodies as a predictive biomarker for selection of amr treatment in lung transplant recipients

P139 Dilution studies establish hla donor-specific antibodies as a predictive biomarker for selection of amr treatment in lung transplant recipients

Fungal infection in lung transplant recipients in perioperative period from one lung transplant center.

This study aimed to analyze the distribution and prophylaxis strategy of pathogens causing fungal infection in lung transplant recipients from cardiac-brain dead donors in the perioperative period to provide evidence for antifungal prophylaxis and treatment in lung transplant recipients. This retrospective study evaluated 194 lung transplant recipients from January 2015 to December 2016. Fungal pathogens were isolated and identified from respiratory tract cultures before and after transplantation in the perioperative period. The galactomannan (GM) testing of bronchoalveolar lavage fluid (BALF) might facilitate the diagnosis of Aspergillus infection. Data were statistically analyzed using SPSS 19.0. A total of 31 cases of fungal strains isolated from the 194 recipients were identified prior to lung transplantation, and the positive rate was 16.0% (31/194). A total of 27 cases of isolated fungal strains in the 194 recipients were identified, and the positive rate after lung transplantation was 13.9% (27/194) in the perioperative period. A total of 54 cases with positive fungal infection (27.8%) were detected before and after lung transplantation. Overall, 10.3% (20/194) of the lung transplant recipients developed fungal infection in the observation period. The most common fungal pathogens were filamentous fungi and Candida albicans. Our data suggested that fungi were frequently isolated before and after transplantation from respiratory samples. However, the incidence of invasive fungal infection in lung transplant recipients in the perioperative period was relatively low. Targeted antifungal prophylaxis and treatment should be applied on the basis of the fungal distribution status of different individuals.

A Study of Renal Function-based Prophylactic Valganciclovir Treatment in Lung Transplant Recipients

A Study of Renal Function-based Prophylactic Valganciclovir Treatment in Lung Transplant Recipients

Diagnostic Value of Peripheral and Bronchoalveolar Leukocyte Profile in Lung Transplant Recipients After Alemtuzumab Induction Therapy. A Single Center Experience

Early diagnosis of lower respiratory tract infection (LRTI) and acute cellular rejection (ACR) is crucial for adequate treatment in lung transplant recipients. A recently described algorithm (Speck 2016) for LRTI and ACR prediction which includes differences in peripheral blood (PBIC) and bronchoalveolar lavage immune cells (BALIC) was tested in LuTX patients treated with alemtuzumab induction therapy.

Challenging immunosuppression treatment in lung transplant recipients with kidney failure

Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a “calcineurin inhibitor-free window” in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3mL/min/1.73m2 and 69mL/min/1.73m2) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results.

The Effectiveness of Culture-Directed Preemptive Anti-Aspergillus Treatment in Lung Transplant Recipients at One Year After Transplant.

Invasive pulmonary aspergillosis (IPA) is a significant complication after lung transplantation. However, the risk factors for IPA in patients colonized with Aspergillus species, and the effectiveness of culture-directed preemptive treatment, are not well known. We studied 328 lung transplant recipients, from January 2006 to July 2009, with 1-year follow-up. Risk factors and effectiveness of culture-directed preemptive treatment were evaluated via a Cox-proportional hazard model. Seventy-one recipients (21.6%) developed invasive fungal infections, including 29 patients (8.8%) with IPA. Only 48.3% (14/29) of patients with IPA had pretransplantation or posttransplantation airway colonization with Aspergillus spp. In the Cox-proportional hazard model, treatment with rabbit antithymocyte globulin was significantly associated with posttransplant IPA in patients with Aspergillus colonization (hazards ratio, 4.25; 95% confidence interval, 1.09-16.6). Preemptive antifungal treatment for 3 months was significantly associated with a lower rate of IPA (0% [0/36] vs 18% [14/77]; P = 0.003, odds ratio, 0.8; 95% confidence interval, 0.7-0.9) but did not impact mortality. Our data suggest that almost half the cases of IPA occurred in patients without pretransplantation or posttransplantation airway colonization with Aspergillus spp. Among patients with Aspergillus colonization, use of rabbit antithymocyte globulin was associated with 4-fold risk of subsequent development of IPA. Invasive pulmonary aspergillosis was an independent risk factor for 1-year mortality. Use of preemptive antifungal treatment for 3 months may be associated with significant reduction of IPA without influencing mortality.

Respiratory syncytial virus: How, why and what to do

Bronchiolitis is the leading cause of hospitalization of infants and young children worldwide. Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Studies conducted using molecular diagnostic assays confirmed that RSV accounts for over 50% of bronchiolitis in young children requiring hospitalization. Those studies demonstrate that it is common to identify RSV in association with a second viral agent but it is yet unclear whether the simultaneous detection of two or even three viruses is associated with increased disease severity. Despite extensive efforts, a vaccine for prevention of RSV infection is not yet available. Palivizumab a humanized monoclonal antibody directed against the F protein of RSV is the only agent licensed to prevent severe RSV disease in high-risk children. Among the new antivirals being developed for treatment of RSV infections, an RNA-interference based agent has demonstrated promising results for treatment of lung transplant recipients with acute RSV infection.

Immunosuppression: What's Standard and What's New?

Lung transplantation is the ultimate treatment option for patients with end-stage lung disease. Chronic rejection, in the form of bronchiolitis obliterans syndrome, and noncytomegalovirus infections are the major causes of morbidity and mortality beyond the first year after transplantation. Most lung transplant recipients are treated lifelong with a three-drug immunosuppression regimen consisting of a calcineurin inhibitor, an antimetabolite, and low-dose corticosteroids. However, induction and maintenance immunosuppression strategies vary widely between centers, and a consensus on the ideal management of this patient population remains elusive. Over the past 20 years, several studies comparing the calcineurin inhibitors cyclosporine and tacrolimus and other studies comparing the antimetabolites azathioprine and mycophenolate mofetil have been performed. Additionally, the role of mammalian target of rapamycin (mTOR) inhibitors in the treatment of lung transplant recipients and the utility of azithromycin to treat and prevent bronchiolitis obliterans syndrome are areas of active investigation. This review discusses induction and traditional maintenance immunosuppressive agents and regimens and the evidence that exists to help guide therapy. Newer research involving the use of mTOR inhibitors in place of calcineurin inhibitors or antimetabolites and azithromycin for the treatment and prevention of bronchiolitis obliterans syndrome is also explored.

Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients

Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without causing adverse effects. To assess the benefits and harms of tacrolimus versus cyclosporin for primary immunosuppression in lung transplant recipients. We searched the Cochrane Renal Group's Specialised Register to 10 April 2013 through contact with the Trials Search Co-ordinator using search terms relevant to this review. We also searched Science Citation Index Expanded and the Transplant Library to 20 April 2013. We included all randomised controlled trials (RCT) that compared any dose and duration of administration of tacrolimus versus cyclosporin as primary immunosuppressive treatment in lung transplant recipients. Our selection criteria required that all included patients received the same additional immunosuppressive therapy within each study. Three authors extracted data. For dichotomous data we used risk ratio (RR) and used mean difference (MD) for continuous data, each with 95% confidence intervals (CI). Methodological components of the included studies were used to assess risk of systematic errors (bias). Trial sequential analysis was used to assess risk of random errors (play of chance). We included three studies that enrolled a total of 413 adult patients that compared tacrolimus with microemulsion or oral solution cyclosporin. All studies were found to be at high risk of bias. Tacrolimus seemed to be significantly superior to cyclosporin regarding the incidence of bronchiolitis obliterans syndrome (RR 0.46, 95% CI 0.29 to 0.74), lymphocytic bronchitis score (MD -0.60, 95% CI -1.04 to -0.16), treatment withdrawal (RR 0.27, 95% CI 0.16 to 0.46), and arterial hypertension (RR 0.67, 95% CI 0.50 to 0.89). However, the finding for arterial hypertension was not confirmed when analysed using a random-effects model (RR 0.54, 95% CI 0.17 to 1.73). Furthermore, trial sequential analysis found that none of the meta-analyses reached the required information sizes and cumulative Z-curves did not cross trial sequential monitoring boundaries. Diabetes mellitus occurred more frequently among people in the tacrolimus group compared with the cyclosporin group when the fixed-effect model was applied (RR 4.24, 95% CI 1.58 to 11.40), but no difference was found when the random-effects model was used for analysis (RR 4.43, 95% CI 0.75 to 26.05). Again, trial sequential analysis found that the required information threshold was not reached and cumulative Z-curve did not cross the trial sequential monitoring boundary. No significant difference between treatment groups was observed regarding mortality (RR 1.06, 95% CI 0.75 to 1.49), incidence of acute rejection (RR 0.89, 95% CI 0.77 to 1.03), numbers of infections/100 patient-days (MD -0.15, 95% CI -0.30 to 0.00), cancer (RR 0.21, 95% CI 0.04 to 1.16), kidney dysfunction (RR 1.41, 95% CI 0.93 to 2.14), kidney failure (RR 1.57, 95% CI 0.28 to 8.94), neurotoxicity (RR 7.06, 95% CI 0.37 to 135.19), and hyperlipidaemia (RR 0.60, 95% CI 0.30 to 1.20). Trial sequential analysis showed the required information thresholds were not reached for any of these outcome measures. Tacrolimus may be superior to cyclosporin regarding bronchiolitis obliterans syndrome, lymphocytic bronchitis, treatment withdrawal, and arterial hypertension, but may be inferior regarding development of diabetes. No difference in mortality and acute rejection was observed between patients treated with tacrolimus and cyclosporin. There were few studies comparing tacrolimus and cyclosporin after lung transplantation, and the numbers of patients and events in the included studies were limited. Furthermore, the included studies were deemed to be at high risk of bias. Hence, more RCTs are needed to assess the results of the present review. Such studies ought to be conducted with low risks of systematic errors (bias) and of random errors (play of chance).

Decreased incidence of cytomegalovirus infection with sirolimus in a post hoc randomized, multicenter study in lung transplantation

Cytomegalovirus (CMV) is the most common opportunistic infection in lung transplantation. A recent multicenter, randomized trial (the AIRSAC study) comparing sirolimus to azathioprine in lung transplant recipients showed a decreased incidence of CMV events in the sirolimus cohort. To better characterize this relationship of decreased incidence of CMV events with sirolimus, we examined known risk factors and characteristics of CMV events from the AIRSAC database. The AIRSAC database included 181 lung transplant patients from 8 U.S.-based lung transplant centers that were randomized to sirolimus or azathioprine at 3 months post-transplantation. CMV incidence, prophylaxis, diagnosis and treatment data were all prospectively collected. Prophylaxis and treatment of CMV were at the discretion of each institution. The overall incidence of any CMV event was decreased in the sirolimus arm when compared with the azathioprine arm at 1 year after lung transplantation (relative risk [RR] = 0.67, confidence interval [CI] 0.55 to 0.82, p < 0.01). This decreased incidence of CMV events with sirolimus remained significant after adjusting for confounding factors of CMV serostatus and CMV prophylaxis. These data support results from other solid-organ transplantation studies and suggest further investigation of this agent in the treatment of lung transplant recipients at high risk for CMV events.

Long-term azithromycin therapy for bronchiolitis obliterans syndrome: Divide and conquer?

Azithromycin may reverse or halt the decline of pulmonary function (FEV(1)) in bronchiolitis obliterans syndrome (BOS). In this study we investigated the effects of long-term azithromycin treatment in lung transplant recipients with BOS. A retrospective, observational, cohort study was performed on 107 patients with BOS (Stages 0p/1/2/3, n = 23/62/20/2), who were treated with azithromycin for 3.1 ± 1.9 years. Patients were evaluated 6.3 ± 3.8 years after transplantation and assessed for evolution of FEV(1), bronchoalveolar lavage neutrophilia and overall survival after initiation of azithromycin. Survival curves were analyzed using the log-rank test. Cox proportional hazard survival regression analysis was performed to estimate hazard ratios of clinical variables predicting outcome. FEV(1) increased ≥ 10% after 3 to 6 months of treatment in 40% of patients, of whom 33% later redeveloped BOS. FEV(1) further declined in 78% and stabilized in 22% of the remaining non-responders. Pre-treatment neutrophilia was higher in responders: 29.3% (9.3% to 69.7%) vs 11.5% (2.9% to 43.8%) (p = 0.025), in whom it significantly decreased to 4.2% (1.8% to 17.6%) (p = 0.041) after 3 to 6 months of azithromycin. Responders demonstrated better survival compared with non-responders (p = 0.050), with 6 and 21 patients, respectively, dying during follow-up (p = 0.027). Multivariate analysis identified initial azithromycin response and earlier post-transplant initiation of azithromycin to be protective for both BOS progression/relapse (hazard ratio [HR] = 0.12 [95% confidence interval 0.05 to 0.28], p < 0.0001; and HR = 0.98 [95% confidence interval 0.97 to 0.98], p < 0.0001, respectively) and retransplantation/death during follow-up (HR 0.10 [95% confidence interval 0.02 to 0.48], p = 0.004; and HR 0.96 [95% confidence interval 0.95 to 0.98], p < 0.0001, respectively). Long-term azithromycin benefits pulmonary function and survival in BOS, particularly in patients with increased lavage neutrophilia.

Surfactant as salvage therapy in life threatening primary graft dysfunction in lung transplantation

Impaired surfactant activity may contribute to primary graft dysfunction after lung transplantation. We assessed the role of surfactant treatment in lung transplant recipients with severe life threatening primary lung graft dysfunction. Five patients after lung transplantation: 4 after single-lung transplantation, for emphysema (n=3) or idiopathic pulmonary fibrosis (n=1), and 1 patient after double-lung transplantation for cystic fibrosis. All had severe life threatening primary graft dysfunction that failed to respond to conventional measures. Treatment consisted of bronchoscopic instillation of mammalian surfactant, 20-90cc, at 3 (n=1) or 7 days (n=4) after transplantation. There was a significant improvement in the ratio of partial arterial oxygen tension (PaO(2)) to fractional concentration of oxygen in inspired gas (FIO(2)), from a mean of 98.8+/-21.7 to 236.8+/-52.3 mmHg (p=0.0006), within hours of treatment. All were eventually discharged home and showed a satisfactory FEV(1) (44-67% predicted) at the 6-month follow-up. All patients were still alive 6 months or more after transplantation. Surfactant treatment improves oxygenation and may be life saving in patients with primary lung graft dysfunction.

Lamivudine Prophylaxis for Hepatitis B Virus Infection After Lung Transplantation

Several reports have shown the efficacy of prophylactic lamivudine treatment for hepatitis B virus (HBV) infection in liver and renal transplantations. No data are available, however, after lung transplantation. We report our experience with prophylactic lamivudine treatment in lung transplant recipients with HBV infection or when the donor was HBc antibody positive. All our 120 lung transplant recipients and their donors were routinely screened for HBV markers. All recipients who tested positive for hepatitis B surface antigen and negative for HBV-DNA, or had organs from donors who tested positive for hepatitis B core antibody, were treated prophylactically with lamivudine for 12 months after lung transplantation. Patients whose liver functions became abnormal during follow-up were tested for HBV serology and HBV-DNA. Eleven of 120 lung transplant recipients (9.2%) were treated with prophylaxis lamivudine. Four recipients were hepatitis B surface antigen positive, and 7 recipients received organs from donors positive for HBc antibodies. Median follow-up after treatment was 24 months. All patients had normal alanine transaminase and undetectable levels of HBV-DNA before treatment. No side effects of lamivudine therapy were reported by any of the patients. Reactivation with alanine transaminase elevation and high HBV-DNA levels occurred in 2 patients. Both of them were recipients positive for hepatitis B surface antigen. In the first patient, lamivudine-resistant strain was detected and adefovir dipivoxil was started. In the other, reactivation developed 2 months after the end of lamivudine treatment. Lamivudine treatment was resumed, with rapid normalization of the HBV-DNA. Use of lamivudine is considered safe for suppressing HBV infection after lung transplantation.

198: Improving outcomes in lung transplantation

Advances in our understanding of primary graft dysfunction (PGD), immunosuppression, and causes of lung allograft injury have resulted in substantial changes in the treatment of lung transplant recipients. We explored the impact of these changes in outcomes following lung transplantation.

Posttransplant Lymphoproliferative Disorder: Incidence, Presentation, and Response to Treatment in Lung Transplant Recipients

Posttransplant lymphoproliferative disorder (PTLD) is a relatively infrequent but devastating complication that occurs after solid-organ transplantation. Although the optimal treatment for this condition is unknown, rituximab, a murine/human chimeric monoclonal antibody, has shown promise in the treatment of PTLD. In this report, we define the incidence, clinical features at presentation, and response to treatment of all cases of PTLD observed at our institution over a 10-year period, including four patients who received treatment with rituximab. A review of all patients who underwent lung or heart-lung transplant at Duke University from 1992 to 2002 was performed (n = 400), and demographic and clinical outcome data were extracted. PTLD was observed in 10 of 400 patients (2.5%). Patients who acquired PTLD were predominantly > 55 years old (8 of 10 patients) and with a native disease of COPD (7 of 10 patients). Diagnosis of PTLD was made a median of 343 days after transplant. The type of transplant and Epstein-Barr virus (EBV) status prior to transplant did not appear to influence the risk for PTLD. Patients presented with thoracic organ involvement (7 of 10 patients), extrapulmonary disease (2 of 10 patients), or both (1 of 10 patients). Histologic subtypes included polymorphic B cell (n = 4), monomorphic B cell (n = 3), B cell without further classification (n = 2), and anaplastic T cell (n = 1). Only one patient responded to reduced immunosuppression alone. Patients treated with surgery or radiation (n = 2) or rituximab (n = 4) had favorable responses to therapy. Both patients treated with chemotherapy died related to complications of treatment and PTLD. Presentation and histologic appearance of PTLD varies considerably among lung transplant recipients. PTLD was more frequent among older patients with COPD, regardless of pretransplant EBV serology. Rituximab appears effective as a first-line therapy for PTLD, but additional studies are needed in order to define its efficacy and side effect profile in this population of patients.