Kinetics of Circulating Plasma Cell-Free DNA in Paediatric Classical Hodgkin Lymphoma

Levels of plasma cell-free DNA (cfDNA) of a large series of children with classical Hodgkin lymphoma (cHL) were evaluated and analyzed at diagnosis and during chemotherapy treatment in relation with clinical characteristics. CfDNA levels in cHL patients were significantly higher compared with controls (p=0.002). CfDNA at diagnosis was correlated with presence of B symptoms (p=0.027) and high erythrocyte sedimentation rate (p=0.049). We found that the increasing of plasma cfDNA after first chemotherapy cycle seems to be associated with a worse prognosis (p=0.049). Levels of plasma cfDNA might constitute an interesting non-invasive tool in cHL patients' management

Additional value of volumetric and texture analysis on FDG PET assessment in paediatric Hodgkin lymphoma: an Italian multicentric study protocol

Introduction Assessment of response to therapy in paediatric patients with Hodgkin lymphoma (HL) by 18F-fluorodeoxyglucose positron emission tomography/CT has become a powerful tool for the discrimination of responders from non-responders. The addition of volumetric and texture analyses can be regarded as a valuable help for disease prognostication and biological characterisation. Based on these premises, the Hodgkin Lymphoma Study Group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) has designed a prospective evaluation of volumetric and texture analysis in the Italian cohort of patients enrolled in the EuroNet-PHL-C2.Methods and analysis The primary objective is to compare volumetric assessment in patiens with HL at baseline and during the course of therapy with standard visual and semiquantitative analyses. The secondary objective is to identify the impact of volumetric and texture analysis on bulky masses. The tertiary objective is to determine the additional value of multiparametric assessment in patients having a partial response on morphological imaging.The overall cohort of the study is expected to be round 400–500 patients, with approximately half presenting with bulky masses. All PET scans of the Italian cohort will be analysed for volumetric assessment, comprising metabolic tumour volume and total lesion glycolysis at baseline and during the course of therapy. A dedicated software will delineate semiautomatically contours using different threshold methods, and the impact of each segmentation techniques will be evaluated. Bulky will be defined on contiguous lymph node masses ≥200 mL on CT/MRI. All bulky masses will be outlined and analysed by the same software to provide textural features. Morphological assessment will be based on RECIL 2017 for response definition.Ethics and dissemination The current study has been ethically approved (AIFA/SC/P/27087 approved 09/03/2018; EudraCT 2012-004053-88, EM-04). The results of the different analyses performed during and after study completion the will be actively disseminated through peer-reviewed journals, conference presentations, social media, print media and internet

Plasma Cell-Free DNA in Paediatric Lymphomas

licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2013.03.11; Accepted: 2013.04.08; Published: 2013.04.16 Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells. Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics. Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among differen

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spectrometry (LC-MS/MS) on plasma collected at diagnosis from 12 children (age 12–16 years) with nodular sclerosis HL, including six in whom the disease relapsed within 5 years of treatment in the LH2004 trial. Plasma proteins were pooled in groups of three, separately for non-relapsing and relapsing HL, and differentially abundant proteins between the two disease states were identified by LC-MS/MS in an explorative and validation design. Proteins with a fold change in abundance >1.2 or ≤0.8 were considered “differentially abundant”. LC-MS/MS identified 60 and 32 proteins that were more abundant in non-relapsing and relapsing HL plasma, respectively, in the explorative phase; these numbers were 39 and 34 in the validation phase. In both analyses, 11 proteins were more abundant in non-relapsing HL (e.g., angiotensinogen, serum paraoxonase/arylesterase 1, transthyretin), including two previously identified by difference gel electrophoresis (antithrombin III and α-1-antitrypsin); seven proteins were more abundant in relapsing HL (e.g., fibronectin and thrombospondin-1), including two previously identified proteins (fibrinogen β and γ chains). The differentially abundant proteins participated in numerous biological processes, which were manually grouped into 10 biological classes and 11 biological regulatory subclasses. The biological class Lipid metabolism, and its regulatory subclass, included angiotensinogen and serum paraoxonase/arylesterase 1 (more abundant in non-relapsing HL). The biological classes Immune system and Cell and extracellular matrix architecture included fibronectin and thrombospondin-1 (more abundant in relapsing HL). These findings deepen our understanding of the molecular scenario underlying responses to therapy and provide new evidence about these proteins as possible biomarkers of relapse in pediatric HL