Aggressive B-cell lymphomas are a heterogeneous group of mature B-cell neoplasms with morphological similarities, but phenotypic and genetic differences. This thesis investigated the aggressive lymphomas from bench-to-bedside aiming to enhance insight into its pathobiology, to investigate mechanisms underlying therapy resistance, and to explore novel treatment combinations. We focused on the role of MYC gene rearrangements, impact of DNA mutations, and altered protein expression. We observed that MYC rearrangements functioned as drivers of transformation in one third of cases in transformed follicular lymphoma. Next, we described loss of human...

Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lymphocytic leukemia, potentially hampering combination treatment with this drug. We conducted a phase 1-2 study to evaluate the efficacy and safety of six cycles of chlorambucil (7 mg/m(2) daily), rituximab (375 mg/m(2) cycle 1 and 500 mg/m(2) cycles 2-6) and individually-dosed lenalidomide (escalated from 2.5 mg to 10 mg) (induction-I) in first-line treatment of patients with chronic lymphocytic leukemia unfit for treatment with fludarabine, cyclophosphamide and...

Introduction and aim: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, associated with significant morbidity and mortality. In this systematic review we evaluated the clinical performance of advanced imaging modalities at diagnosis and treatment response evaluation of PTLD patients after solid organ and hematopoietic stem cell transplantation. Methods: We have carried out a literature search until December 15, 2017 using PubMed/Medline, Embase, “Web of Science” and Cochrane Library databases concerning the performance of computed tomography (CT), magnetic resonance imaging (MRI)...

Current genomic models in diffuse large B-cell lymphoma (DLBCL) are based on single tumor biopsies, which might underestimate heterogeneity. Data on mutational evolution largely remains unknown. An exploratory study using whole exome sequencing on paired (primary and relapse) formalin fixed paraffin embedded DLBCL biopsies (n = 14) of 6 patients was performed to globally assess the mutational evolution and to identify gene mutations specific for relapse samples from patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. A minority of the mutations detected in the primary sample (median...

PURPOSE: This study aims to investigate whether clinical, laboratory, and fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT findings can discriminate between mediastinal Hodgkin’s lymphoma and primary mediastinal B-cell lymphoma (PMBCL). PATIENTS AND METHODS: This retrospective study included 56 patients (42 with mediastinal Hodgkin’s lymphoma and 14 with PBMCL). Differences in clinical, laboratory, and F-FDG PET/CT metrics were assessed between Hodgkin’s lymphoma and PMBCL. RESULTS: Lactate dehydrogenase (LDH) and F-FDG PET/CT-based maximum tumor diameter, lesion-to-liver ratio maximum standardized uptake value (SUVmax), and lesion-to-liver ratio peak standardized uptake value (SUVpeak) were all significantly higher...