Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial.

We investigated rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (n=662) or follicular lymphoma grade 3b (n=21) in first complete remission. Patients were randomized to rituximab maintenance (n=338) or observation (n=345). At a median follow-up of 45 months, the event-free survival rate (the primary endpoint) at 3 years was 80.1% for rituximab maintenance versus 76.5% for observation. This difference was not statistically significant for the intent-to-treat population (likelihood ratio P=0.0670). The hazard ratio by treatment arm was 0.79 (95% confidence interval 0.57-1.08; P=0.1433). The secondary endpoint, progression-free survival was also not met for the whole statistical model (likelihood ratio P=0.3646). Of note, rituximab maintenance was superior to observation when treatment arms only were compared (hazard ratio: 0.62; 95% confidence interval 0.43-0.90; P=0.0120). Overall survival remained unchanged (92.0 versus 90.3%). In subgroup analysis male patients benefited from rituximab maintenance with regards to both event-free survival (84.1% versus 74.4%) (hazard ratio: 0.58; 95% confidence interval 0.36-0.94; P=0.0267) and progression-free survival (89.0% versus 77.6%) (hazard ratio: 0.45; 95% confidence interval 0.25-0.79; P=0.0058). Women had more grade 3/4 adverse events (P=0.0297) and infections (P=0.0341). Men with a low International Prognostic Index treated with rituximab had the best outcome. In summary, rituximab maintenance in first remission after R-CHOP-like treatment did not prolong event-free, progression-free or overall survival of patients with aggressive B-non-Hodgkin lymphoma. The significantly better outcome of men warrants further studies prior to the routine use of rituximab maintenance in men with low International Prognostic Index. This trial is registered under EUDRACT #2005-005187-90 and www.clinicaltrials.gov as #NCT00400478.

Primary cutaneous follicle center lymphoma with diffuse CD30 expression: a report of 4 cases of a rare variant.

BACKGROUND: CD30 is expressed in aggressive and Epstein-Barr virus-associated forms of B-cell non-Hodgkin lymphomas, but is rarely expressed by the majority of tumor cells in primary cutaneous B-cell lymphomas (CBCLs). The expression of CD30 in CBCLs may be at risk for misinterpretation as an unequivocal indicator of a highly aggressive form of the disease. OBJECTIVE: We report 4 cases of low malignant primary cutaneous follicle center lymphoma (PCFCL) with diffuse and strong expression of CD30 by the majority of neoplastic cells. RESULTS: The patients included 3 men and 1 woman with tumors on the scalp (3 patients) and chest wall (1 patient). The histologic examinations revealed a mixed, diffuse, and follicular growth pattern with CD20(+), bcl-6(+), and bcl-2(-) tumor cells. Seventy percent to 90% of the tumor cells expressed CD30. Clonal rearrangement of immunoglobulin heavy chain genes was found in 1 of 4 cases. None of the 3 cases yielded positivity for Epstein-Barr virus RNA. LIMITATIONS: The study is limited by the small number of patients. CONCLUSIONS: This rare variant of CD30(+) PCFCL needs be distinguished from CD30(+) aggressive B-cell lymphomas. CD30 in this variant of CBCLs may serve as a therapeutic target for anti-CD30 antibody-based strategies.

Extranodal Diffuse Large B-cell Lymphoma With Primary Clinical Presentation as Acute Cholecystitis: A Case Report.

This case describes a rare presentation of a diffuse large B-cell lymphoma not otherwise specified (DLBC NOS) in the gallbladder. We report the case of an 89-year-old male who initially presented with a two-week history of weakness and abdominal discomfort. We performed laparoscopic cholecystectomy for suspicion of acute cholecystitis. After the initial uneventful course, readmission occurred for persisting weakness a few weeks after surgery. Computed tomography revealed progressive retroperitoneal lymphadenopathy. With new emerging neurological symptoms, taking into account the histopathological findings of the gallbladder specimen, the diagnosis of DLBCL NOS was confirmed. Due to the rapid clinical deterioration and extranodal involvement, the patient opted against further therapy. When the suspicion of cholecystitis is inconclusive, rare differential diagnoses need to be considered. This analysis may improve the understanding of the presentation and course of DLBC NOS in abdominal organs and could form the basis for a systematic review to improve diagnosis and therapy.

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.

Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project.

BACKGROUND: Extranodal natural killer (NK) T-cell lymphoma (ENKTL) is a unique clinicopathological entity, typically associated with poor survival outcomes. Most published data have come from east Asian study groups, with little information available from international cohorts. The effects of treatment advances on routine clinical practice across continental territories has not been clear. We aimed to improve understanding of the clinical characteristics and outcomes of patients with ENKTL. METHODS: We did a substudy of patients with ENKTL from the T-cell Project, a global prospective cohort study. The T-cell Project registered consecutively diagnosed adults (>18 years) with newly diagnosed, untreated mature T-cell or NK lymphomas (WHO 2001 or 2008 classifications) from 74 centres in 13 countries (in Asia, Europe, North America, and South America). In total, 1695 patients with mature T-cell or NK lymphomas were enrolled between Oct 12, 2006 and Feb 28, 2018 in the T-cell Project. The first patient with ENKTL was enrolled on Feb 15, 2007, and the last on May 26, 2017. Data on baseline characteristics, first-line treatment, treatment response, and survival outcomes were recorded in a central database (locked March 30, 2019). The primary outcome was 5-year overall survival. The T-cell Project is registered on ClinicalTrials.gov, NCT01142674. FINDINGS: 166 patients were diagnosed with ENKTL, comprising 11% of 1553 eligible registered cases and distributed across 40 participating centres in four continents. At a median follow-up of 44 months (IQR 20-61), overall survival at 5 years was 54% (95% CI 44-63) in patients with nasal disease (n=98) and 34% (27-46) in patients with extranasal disease (n=68). INTERPRETATION: To our knowledge, this study presents the largest international cohort of patients with ENKTL. We describe a clinically significant improvement in the survival of patients with ENKTL treated in routine clinical practice over the past decade, likely to be attributable to the increasing use of treatment protocols specific for ENKTL. FUNDING: The Fondazione Cassa di Risparmio di Modena, the Associazione Angela Serra per la Ricerca sul Cancro, the Fondazione Italiana Linfomi, Allos Therapeutics, Spectrum Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro, and the National Cancer Institute at the National Institutes of Health.

ALK-negative anaplastic large cell lymphoma arising in the thrombus of an aortic prosthesis preceeded by clonally related lymphomatoid papulosis.

We report on a 73-year-old male patient with recurrent thrombosis of his infrarenal aortic prosthesis. Histologically, the thrombus contained cells of an ALK-negative anaplastic large cell T cell lymphoma (ALCL). Imaging studies were negative for other lymphoma manifestations; however, 3 months before, the patient had developed skin lesions consistent with lymphomatoid papulosis type A (LypA) which were clonally related to the ALCL. Due to recurrent thrombosis of larger peripheral arteries with the presence of ALCL cells in the thrombi, the patient is now referred to systemic chemotherapy. We present the first case of ALCL manifesting in the thrombus of an aortic prosthesis. This case shows similarities to the well-established entity of breast implant-associated ALCL and anecdotal reports of ALCL occurring at the site of foreign material implants. These cells show a peculiar propensity to aggregate in vessels and thrombi, known primarily from subtypes of diffuse large B cell lymphomas associated with chronic inflammation.

Treatment of Relapsed/Refractory Hodgkin Lymphoma: Real-World Data from the Czech Republic and Slovakia.

Introduction: Clinical trials have demonstrated the effectiveness of the CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) for the treatment of relapsed/refractory Hodgkin lymphoma (R/R HL). In this study, we report on outcomes with BV in a real-world setting using data collected in clinics in the Czech Republic and Slovakia. Patients and Methods: Clinical and epidemiological data for patients with R/R HL who received treatment with BV at eight centers across the Czech Republic and Slovakia were examined. Data were amalgamated and analyzed retrospectively. Results: Clinical data for 58 patients (median age: 30.5 years) with R/R HL who received BV during the course of their treatment were collected and analyzed. Patients had received a median of 3 prior treatment regimens and most (91%) were treated with BV after relapse following autologous stem cell transplantation. Therapeutic responses after BV included 19 (33%) complete responses (CRs) and 8 (14%) partial responses. CRs occurred more frequently in patients who had received fewer prior treatment regimens. The 1-, 2-, and 3-year overall survival (OS) rates from initiation of BV were 78%, 62%, and 41%, respectively. Conclusion: Response rates and OS in this analysis of BV in real-world settings in the Czech Republic and Slovakia were consistent with those reported for pivotal clinical trials and from previous studies outside the clinical trial setting. The results support the efficacy of BV for treatment of R/R HL in real-life clinical practice.

Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin's Study Group.

PURPOSE: With improved prognosis for patients with Hodgkin's lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis using the German Hodgkin's Study Group (GHSG) database to determine clinical risk factors, course of treatment, and outcome in elderly HL patients in comparison with younger adults. PATIENTS AND METHODS: A total of 4,251 patients included in the GHSG studies HD5 to HD9 were analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, freedom from treatment failure (FFTF), and overall survival (OS) were compared. RESULTS: Elderly patients more often had mixed cellularity subtype, "B" symptoms, elevated erythrocyte sedimentation rate, and poorer performance status. Less frequently observed were nodular sclerosis subtype, large mediastinal mass, and bulky disease. Acute toxicity during chemotherapy was generally higher in elderly patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%) correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%). As a result, significantly fewer elderly patients received the intended full chemotherapy dose (75% v 91%). The survival analysis showed a significantly poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%), FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). CONCLUSION: Elderly patients have a poorer risk profile compared with younger HL patients and experience more severe treatment-associated toxicity. Higher mortality during treatment as well as lower dose-intensity are the major factors explaining the poorer overall outcome of elderly HL patients.