International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia.

Most patients with chronic lymphocytic leukemia (CLL) are diagnosed with early-stage disease and managed with active surveillance. The individual course of patients with early-stage CLL is heterogeneous, and their probability of needing treatment is hardly anticipated at diagnosis. We aimed at developing an international prognostic score to predict time to first treatment (TTFT) in patients with CLL with early, asymptomatic disease (International Prognostic Score for Early-stage CLL [IPS-E]). Individual patient data from 11 international cohorts of patients with early-stage CLL (n = 4933) were analyzed to build and validate the prognostic score. Three covariates were consistently and independently correlated with TTFT: unmutated immunoglobulin heavy variable gene (IGHV), absolute lymphocyte count higher than 15 × 109/L, and presence of palpable lymph nodes. The IPS-E was the sum of the covariates (1 point each), and separated low-risk (score 0), intermediate-risk (score 1), and high-risk (score 2-3) patients showing a distinct TTFT. The score accuracy was validated in 9 cohorts staged by the Binet system and 1 cohort staged by the Rai system. The C-index was 0.74 in the training series and 0.70 in the aggregate of validation series. By meta-analysis of the training and validation cohorts, the 5-year cumulative risk for treatment start was 8.4%, 28.4%, and 61.2% among low-risk, intermediate-risk, and high-risk patients, respectively. The IPS-E is a simple and robust prognostic model that predicts the likelihood of treatment requirement in patients with early-stage CLL. The IPS-E can be useful in clinical management and in the design of early intervention clinical trials.

Prognostic value of POD24 validation in follicular lymphoma patients initially treated with chemotherapy-free regimens in a pooled analysis of three randomized trials of the Swiss Group for Clinical Cancer Research (SAKK).

The relapse of follicular lymphoma (FL) within 24 months (POD24) of chemoimmunotherapy has been associated with poor survival. We analyzed a pooled dataset of three randomized trials including FL patients with advanced disease, conducted by the Swiss Group for Clinical Cancer Research (SAKK). Overall, POD24 was observed in 27% of 318 patients, but rate variance among studies suggested that the rituximab schedule might affect POD24 rate. POD24 was associated with lower 10-year overall survival rates than in the reference group (69% vs. 77%; hazard ratio, 3·12; 95% confidence interval, 1·73-5·65). POD24 retains its prognostic validity in patients treated without chemotherapy and may represent a useful end-point for future studies.

Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy.

The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥90%). Toxicity grade ≥3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored. This trial was registered at www.clinicaltrials.gov as #NCT01307605.

Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma.

The rarity of neoplastic cells in the biopsy imposes major technical hurdles that have so far limited genomic studies in classical Hodgkin lymphoma (cHL). By using a highly sensitive and robust deep next-generation sequencing approach for circulating tumor DNA (ctDNA), we aimed to identify the genetics of cHL in different clinical phases, as well as its modifications on treatment. The analysis was based on specimens collected from 80 newly diagnosed and 32 refractory patients with cHL, including longitudinal samples collected under ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy and longitudinal samples from relapsing patients treated with chemotherapy and immunotherapy. ctDNA mirrored Hodgkin and Reed-Sternberg cell genetics, thus establishing ctDNA as an easily accessible source of tumor DNA for cHL genotyping. By identifying STAT6 as the most frequently mutated gene in ∼40% of cases, we refined the current knowledge of cHL genetics. Longitudinal ctDNA profiling identified treatment-dependent patterns of clonal evolution in patients relapsing after chemotherapy and patients maintained in partial remission under immunotherapy. By measuring ctDNA changes during therapy, we propose ctDNA as a radiation-free tool to track residual disease that may integrate positron emission tomography imaging for the early identification of chemorefractory patients with cHL. Collectively, our results provide the proof of concept that ctDNA may serve as a novel precision medicine biomarker in cHL.

Primary Cutaneous Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma.

Large B-cell lymphomas include several subtypes. Recently, anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma has been delineated as a distinct entity involving mostly lymph nodes and rarely affecting extranodal sites. We describe the first case of a primary cutaneous ALK-positive large B-cell lymphoma in a 48-year-old man with a solitary nodule on the back, and describe the histologic and phenotypic features. Accurate staging confirmed the absence of other lesions, and so surgical excision and postoperative local radiation therapy were initiated and resulted in complete remission. Two years later, extracutaneous spread with involvement of axillary lymph nodes occurred. Complete remission was achieved again by multiagent chemotherapy. Our case demonstrates that a primary cutaneous form of ALK-positive large B-cell lymphoma exists. The immunophenotypic analysis of cutaneous large B-cell lymphomas affecting the skin primarily or secondarily should include the assessment of ALK expression.

The 2016 revision of the World Health Organization classification of lymphoid neoplasms.

A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations, and therapeutic strategies for the lymphoid neoplasms.

Multicenter Phase II Study of Panitumumab in Platinum Pretreated, Advanced Head and Neck Squamous Cell Cancer.

LESSONS LEARNED: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies. BACKGROUND: The objective of this study was to investigate the efficacy and safety of panitumumab (anti-epidermal growth factor receptor [EGFR] antibody) given as a single agent in platinum-pretreated head and neck squamous cell cancer (HNSCC). METHODS: Patients with advanced HNSCC previously treated with platinum-containing therapy were included. Panitumumab was administered intravenously every 2 weeks at a dose of 6 mg/kg. Primary endpoint was overall response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; secondary endpoints were progression-free survival (PFS) and safety. A Simon's two-step design was chosen; 4 partial remissions (PR) in the first 32 patients were required for continuing to step two. An exploratory biomarker analysis was performed. RESULTS: Thirty-three patients were enrolled. Two patients obtained a PR for an ORR of 6%, and 15 (45%) showed stable disease (SD) for at least 2 months, resulting in a 51% disease control rate. Median PFS was 2.6 months (95% confidence interval [CI]: 1.7-3.7), while median OS was 9.7 months (95% CI: 6.3-17.2). The most frequent adverse drug reactions were cutaneous rash (64%) and hypomagnesemia (55%). Overall, 30% of patients experienced grade 3/4 adverse events. No infusion-related reactions occurred. EGFR copy number gain (CNG) was more frequent in patients who benefitted from panitumumab. Two uncommon KRAS mutations (G48E, T50I) and 3 canonical PIK3CA mutations (all E545K) were detected. High-risk HPV16 was found in 10 patients and EGFR CNG in 13 treated patients. EGFR CNG seems to be more frequent in individuals with at least SD compared with patients with progressive disease (59% vs. 30%). PFS for patients with EGFR CNG was 4.6 months (95% CI: 1.0-9.2 months) and 1.9 months (95% CI: 1.0-3.2 months) for patients without CNG (p = .02). CONCLUSION: Panitumumab monotherapy in pretreated HNSCC patients was well tolerated but moderately active. We observed a considerable disease control rate. Future strategies with this agent comprise right patient selection through the identification of reliable biomarkers and gene signatures predicting response and, considering good tolerability and convenience, combination strategies with novel agents and immune therapeutic agents.

Y90 -Ibritumomab tiuxetan (Y90 -IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05).

Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y90 -Ibritumomab tiuxetan (Y90 -IT) is well tolerated and feasible in the transplantation setting. We therefore investigated the combination of high-dose melphalan and Y90 -IT as a conditioning regimen for patients ≥65 years of age. Patients with relapsed or resistant CD20-positive lymphoma in remission after salvage chemotherapy could be enrolled. High-dose therapy consisted of standard dose Y90 -IT (0.4-mCi/kg body weight) followed by melphalan at escalating doses (100, 140, 170 and 200 mg/m2 ) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3 dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were infection (n = 6), including 2 cases of febrile neutropenia, diarrhea (n = 3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration, and multiorgan failure (n = 1 for each). The combination of Y90 -IT and high-dose melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity.

Prognostic impact of monocyte count at presentation in mantle cell lymphoma.

An increased number of circulating monocytes at presentation has recently been associated with shorter survival in Hodgkin lymphoma, follicular lymphoma and diffuse large B cell lymphoma. This study aimed to assess the prognostic impact of the absolute monocyte count (AMC) at diagnosis in mantle cell lymphoma (MCL). AMC at diagnosis was available in 97 MCL cases recorded in the databases of the Oncology Institute of Southern Switzerland in Bellinzona (Switzerland) and the Division of Haematology of the Amedeo Avogadro University of Eastern Piedmont in Novara (Italy). With a median follow up of 7 years, the 5-year overall survival was 29% for patients with AMC >0·50 × 10(9) /l and 62% for patients with AMC ≤0·50 × 10(9) /l (P = 0·008). Elevated AMC and beta-2 microglobulin at diagnosis remained independent outcome predictors at multivariate analysis, controlling for the MCL International Prognostic Index (MIPI), and have been used to build a simple prognostic scoring system. In this relatively small and heterogeneous series an increased AMC identified poor-risk patients. Our results suggest that AMC together with the beta-2 microglobulin level might provide an inexpensive way to stratify MCL patient risk as a complement to the MIPI, which was confirmed to be a very powerful prognostic tool.

Bendamustine in indolent non-Hodgkin's lymphoma: a practice guide for patient management.

For patients with advanced indolent non-Hodgkin's lymphoma (NHL) or elderly patients with mantle cell lymphoma (MCL), the recently reported results of the German StiL NHL-1 2003 and the international BRIGHT phase III trials showed that, as first-line treatment, the combination of bendamustine and rituximab is at least as effective as rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone or rituximab/cyclophosphamide/vincristine/prednisone, possibly with a better therapeutic index. Bendamustine is therefore increasingly used in clinical practice. Because bendamustine has been used for many years in Germany and in Switzerland, our institutions have had extensive experience with bendamustine, both as a single agent and in combination with rituximab. In this comprehensive review, we summarize the most important clinical data from phase II/III trials with bendamustine in patients with indolent NHL and MCL, both in the relapsed/refractory setting and in the first-line setting. In addition, this review provides practical advice on how to optimally manage bendamustine therapy in patients with NHL.

Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma: a consensus project of the EBMT-Lymphoma Working Party.

The aim of this project was to define indications for hematopoietic stem cell transplantation in follicular lymphoma in Europe. In the absence of evidence-based data, a RAND-modified Delphi procedure was used by an expert panel. After pre-defining statements, these were individually/anonymously scored by each participant using a 9-point scale. Consensus was reached that: 1) high-dose therapy with autologous stem cell rescue is not an appropriate option to consolidate first remission in patients responding to immuno-chemotherapy outside clinical trials; 2) in patients with first chemo-sensitive relapse, high-dose therapy with autologous stem cell rescue is an appropriate option to consolidate remission, especially in patients with a short response after immuno-chemotherapy or with high-risk FLIPI; 3) high-dose therapy with autologous stem cell rescue is also appropriate in second/subsequent chemo-sensitive relapses; 4) allotransplant (preferably a reduced intensity conditioning-allotransplant) should be considered at relapse after high-dose therapy with autologous stem cell rescue. No consensus was reached on the role of high-dose therapy with autologous stem cell rescue in low-risk first relapse, or on when an allotransplant should be preferred over high-dose therapy with autologous stem cell rescue. In the absence of evidence-based data, the consensus method used was a valuable tool to define indications for hematopoietic stem cell transplant in follicular lymphoma.

Incidence, risk factors and outcome of histological transformation in follicular lymphoma.

Histological transformation (HT) into diffuse large B-cell lymphoma (DLBCL) was documented in 37 of the 281 (13%; 95% CI, 9-18) follicular lymphoma (FL) patients treated at our institute from 1979 to 2007. HT occurred at a median of 2·75 years from initial FL diagnosis and HT rate was 15% at 10 years and 26% at 14 years, with a plateau from that point onward. Patients with bulky or extranodal disease, or those diagnosed before 1990 had a significantly higher risk of HT. When initial treatment strategies were taken into account, a reduced HT risk was seen in the patients initially managed with a 'watch and wait' policy, while the risk appeared significantly increased in the small subset of 18 patients initially managed with rituximab plus chemotherapy (P = 0·0005). HT was associated with a significantly shorter cause-specific survival (P = 0·0002). Predictors of survival after HT were the Follicular Lymphoma International Prognostic Index at diagnosis, as well as age and performance status at the time of HT. Our data confirm the adverse clinical outcome of FL after HT. In keeping with previous isolated reports, our findings suggest that there is a subgroup of patients in whom HT may not occur.

A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma (NCT00516412). DESIGN AND METHODS: Eligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints. RESULTS: Thirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade ≥ 3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8-37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8-8.2) overall and 17.0 (6.4-23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood. CONCLUSIONS: Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted.

Factors Affecting the Clinical Course of Follicular Lymphoma: A Multistate Survival Analysis Using Individual Patient Data from Eight Multicenter Randomized Clinical Trials.

INTRODUCTION/BACKGROUND: Leveraging the Follicular Lymphoma Analysis of Surrogacy Hypothesis database of individual patient data from first-line clinical trials, we studied the clinical course of follicular lymphoma (FL) and investigated clinical factors associated with FL outcomes. PATIENTS AND METHODS: We examined 2428 patients from 8 randomized trials using multistate survival models with 4 states: induction treatment, progression, death from FL, and death from other causes. We utilized Aalen-Johansen estimator and Cox models to assess the likelihood of FL outcomes and quantify predictors' effects. RESULTS: Two-year progression, FL-related death, and death from other causes estimates were 26.5%, 3.4% and 1.4%, respectively. FL-associated deaths were the primary cause of mortality within 10 years of follow-up. Male sex (hazard ratio: 1.25; 95% confidence interval: 1.05-1.47), > 4 involved nodal areas (1.51; 1.23-1.86), elevated LDH (1.20; 1.01-1.43), low hemoglobin (1.44; 1.15-1.81), and elevated ß-2 levels (1.23; 1.02-1.47) increased risk of progression. CD20-targeting agents reduced risks for progression (0.29; 0.22-0.39), death from FL (0.05; 0.01-0.20), and death from other causes without progression (0.13; 0.05-0.33) and following progression (0.52; 0.30-0.92). Estimated 2-year progression rates were 22.3% and 43.5% with or without CD20-targeting agents, respectively. Two-year FL-associated mortality rate was 8.3% among patients without CD20-targeting agents, 5.4% with B-symptoms, 4.9% with elevated LDH, and 9.1% with low hemoglobin. CONCLUSION: This study identified independent contributions of baseline clinical factors to distinct outcomes for patients with FL following first-line therapy on a clinical trial. Similar analytical approaches are needed to increase understanding of factors that influence FL outcomes in other settings.

How I treat mantle cell lymphoma.

Mantle cell lymphoma is included in the World Health Organization classification as distinct lymphoma subtype characterized by the t(11;14)(q13;q32) translocation, which results in overexpression of Cyclin D1. The clinical presentation often includes extranodal involvement, particularly of the bone marrow and gut. The prognosis of patients with mantle cell lymphoma (median overall survival, 3-5 years) is poorest among B-cell lymphoma patients, even though a prospectively difficult to identify subgroup can survive for years with little or no treatment. Conventional chemotherapy is not curative but obtains frequent remissions (60%-90%) which are usually shorter (1-2 years) compared with other lymphoma entities. Very intensive regimens, including autologous and allogeneic stem cell transplantation, seem required to improve the outcome, but with the median age of diagnosis being 60 years or more, such approaches are feasible only in a limited proportion of patients. The possibility of treating patients based on prognostic factors needs to be investigated prospectively.

Controversies in the Treatment of Follicular Lymphoma.

The overall prognosis of patients with follicular lymphoma has substantially improved over the last decades with a 10-year overall survival of around 80% for the majority of patients. However, for most patients follicular lymphoma it is still a relapsing and remitting disease. Furthermore, certain subsets of patients still have much shorter survival. Currently, there is no established standard how to treat high-risk follicular lymphoma. With advances in the understanding of the biology and pathogenesis of B cell malignancies, a plethora of new compounds have been investigated in FL. These compounds have the potential to increase efficacy if added to current regimens or even replace them. The implementation of these compounds in treatment algorithms is another unsolved issue. This overview highlights major controversies in the treatment of follicular lymphoma and discusses the most recent and relevant clinical trials.

Risk factors for renal toxicity after inpatient cisplatin administration.

BACKGROUND: After several decades, cisplatin continues to be an essential drug for the treatment of several tumors, however, its potential nephrotoxicity is still a clinically relevant issue. Identification of predisposing factors for renal toxicity could be of value to warrant prophylactic measures. METHODS: We analyzed data from 198 patients with various tumor types, treated with cisplatin containing regimens in our regional cancer center in a two-years period. Assessed variables included age, gender, smoking status, alcohol consumption, tumor type, prior or concomitant anticancer treatment, cisplatin dose, time-interval between cycles, number of cycles, concomitant nephrotoxic drugs or radiotherapy and co-morbidities. We divided cisplatin nephrotoxicity in two categories: transient and permanent. Univariable and multivariable analyses were performed in order to define statistical associations. RESULTS: Cisplatin discontinuation rate was 27,7%, of which, 8.1% was due to renal toxicity. A total of 74 and 21 patients developed transient and permanent nephrotoxicity, respectively. At univariable analysis cirrhosis (p = 0.027), hypertension (p = 0.020), alcohol intake (p = 0.030) and number of cycles < 4 (p = 0.002) were significantly associated with transient renal toxicity, while at the multivariable analysis, a statistical significance was detected for cirrhosis (p = 0.009), hypertension (p = 0.009) and a total number of cycles < 4 (p = 0.003). Regarding permanent renal toxicity, a concomitant administration of NSAIDs was significant at univariable analysis (p = 0.002). CONCLUSIONS: Relevant risk factors for the development of transient nephrotoxicity were defined. Patients presenting these baseline characteristics may require more frequent post-cycle check-up visits and hydration treatment should be guaranteed as soon as a reduction of creatinine clearance is detected.

Diagnostic Performance of 18F-FDG PET or PET/CT for Detection of Post-Transplant Lymphoproliferative Disorder: A Systematic Review and a Bivariate Meta-Analysis.

BACKGROUND: Some studies evaluated the diagnostic performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography or positron emission tomography/computed tomography (PET or PET/CT) for the detection of post-transplant lymphoproliferative disorder (PTLD). As there is no clear consensus about the diagnostic accuracy of these imaging methods, we performed a meta-analysis on this topic. METHODS: A comprehensive computer literature search of PubMed, Embase, and Cochrane library databases through December 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) of 18F-FDG PET or PET/CT for detection of PTLD were calculated. RESULTS: Five studies reporting data on the diagnostic performance of 18F-FDG PET or PET/CT in 336 transplant recipients were included in the systematic review and bivariate meta-analysis. Pooled sensitivity and specificity for detection of PTLD were 89.7% (95% confidence interval (95%CI): 84.6-93.2%) and 90.9% (95%CI: 85.9-94.3%), respectively. Pooled LR+, LR-, and DOR were 8.9 (95%CI: 5.7-14), 0.13 (95%CI: 0.08-0.2), and 70.4 (95%CI: 35.4-140), respectively. A significant heterogeneity among studies was not detected. CONCLUSIONS: Despite limited literature data, 18F-FDG PET or PET/CT demonstrated good diagnostic performance for the detection of PTLD, but large prospective studies are needed to strengthen these findings.