Polyclonal B-cell lymphocytosis with binucleated lymphocytes (PPBL)

Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare and recently described entity. The review of the literature show PPBL is diagnosed predominantly but not exclusively in women, usually smokers. PPBL is recognized by a moderate, chronic and absolute lymphocytosis (>4 × 109/l) in the peripheral blood. In 10% of cases without lymphocytosis, the PPBL diagnosis has to be suggested by peripheral blood examination showing in all cases atypical binucleated lymphocytes. A polyclonal serum IgM is also associated and HLA-DR7 expression is present in most cases. Contrary to B-cell chronic lymphoproliferative disorders (B-CLPD), peripheral B cells are polyclonal with kappa and lambda light-chain expression and no clonal rearrangement of immunoglobulin heavy chain genes is usually demonstrated. The detection of an extra isochromosome for the long arm of chromosome 3 +i(3)(q10) has to be considered as a specific marker of PPBL. We performed conventional cytogenetic analysis (CCA) in 111 patients with typical PPBL we followed-up more than 4 years. +i(3q) was detected in 34% (33/98), PCC in 8% (8/98) and both abnormalities in 31% (30/98). CCA showed neither +i(3q) nor PCC in 28% (27/98). Fluorescence in situ hybridization (FISH) was also performed in 84 cases and +i(3q) was detected in 71% (60/84). When combining both procedures in 84 patients, +i(3q) was detected in 17 patients with negative CCA and was confirmed in 43 patients with positive CCA. CCA and FISH were both negative in 24 cases. Whether patients with PPBL are at increased risk of hematological malignancy remains unclear. After a median follow-up of 4.4 years, most PPBL patients presented a stable clinical and biological course. Six patients died from pulmonary cancer, myocardial infarction, cerebral aneurysm rupture or diffuse large B-cell lymphoma. Two patients had IgM monoclonal gammopathy of undetermined significance (MGUS) at the time of PPBL diagnosis and two other patients developed IgM MGUS respectively 12 and 22 years after PPBL diagnosis. A malignant non Hodgkin's lymphoma (NHL) appeared in 3 additional patients: two patients presented diffuse large B cell lymphoma and 1 patient a splenic marginal zone lymphoma. In conclusion, the possibility of PPBL to evolve toward a clonal proliferation, malignant lymphoma or secondary solid cancer lead us to consider PPBL not as a benign pathology. We recommend a careful and continued clinical and biological long-term follow-up in all PPBL patients

Behavioural Insights Applied to Policy - European Report 2016

This report covers a wealth of policy initiatives across 32 European countries either implicitly or explicitly informed by behavioural insights (BIs). It reviews institutional developments around the application for behavioural insights for policy and puts forward a comparative framework (PRECIS) describing behavioural insights teams with six key features. The report reaches four main conclusions: i) in terms of capacity-building, there is significant dynamism and growing appetite to apply BIs to policy-making; ii) links between policy-making and academy communities can be strengthened and analysing large datasets offers great potential; iii) systematic application of BIs throughout the policy cycle can advance evidence-based policy-making; iv) there is a need for more research on the long-term impacts of policy interventions.JRC.DDG.02-Foresight and Behavioural Insight

Recommendations of the SFH (French Society of Haematology) for the diagnosis, treatment and follow-up of hairy cell leukaemia

International audienceHairy cell leukaemia (HCL) is a rare haematological malignancy, with approximately 175 new incident cases in France. Diagnosis is based on a careful examination of the blood smear and immunophenotyping of the tumour cells, with a panel of four markers being used specifically to screen for hairy cells (CD11c, CD25, CD103 and CD123). In 2011, the V600E mutation of the BRAF gene in exon 15 was identified in HCL; being present in HCL, it is absent in the variant form of HCL (HCL-v) and in splenic red pulp lymphoma (SRPL), two entities related to HCL. The management of patients with HCL has changed in recent years. A poorer response to purine nucleoside analogues (PNAs) is observed in patients with more marked leukocytosis, bulky splenomegaly, an unmutated immunoglobulin variable heavy chain (IgVH) gene profile, use of VH4-34 or with TP53 mutations. We present the recommendations of a group of 11 experts belonging to a number of French hospitals. This group met in November 2013 to examine the criteria for managing patients with HCL. The ideas and proposals of the group are based on a critical analysis of the recommendations already published in the literature and on an analysis of the practices of clinical haematology departments with experience in managing these patients. The first-line treatment uses purine analogues: cladribine or pentostatin. The role of BRAF inhibitors, whether or not combined with MEK inhibitors, is discussed. The panel of French experts proposed recommendations to manage patients with HCL, which can be used in a daily practice

Long-term follow-up of 111 patients with persistent polyclonal B-cell lymphocytosis with binucleated lymphocytes.

International audienceInitially described in 1982, the persistent polyclonal B-cell lymphocytosis (PPBL) is characterized by a chronic, stable, persistent and polyclonal lymphocytosis, the presence of binucleated lymphocytes in the peripheral blood and a polyclonal increase in serum immunoglobulin-M (IgM). In this apparently benign entity, we showed that PPBL was associated with recurrent chromosomal abnormalities and a typical cytogenetic profile including isochromosome 3q, +i(3q), premature chromosome condensation (PCC), both abnormalities in the same patient or chromosomal instability. Despite clinical and polyclonal lymphocytosis stability, the long-term follow-up is not yet well established.We analyse and report here the long-term follow-up of 111 patients with typical PPBL

Gaps and challenges in the knowledge of migration and demography: Proposals for new approaches and solutions

This report is the result of the research carried out under Task 5 of DG JRC's Task Force on Migration and Demography. The report is structured following the four pillars outlined in the European Agenda on Migration. A few additional chapters are included to cover some aspects not explicitly touched on in the Agenda, but still considered to have a relevant role in migration and an impact on demographic trends. Contributions answered the following questions: 1. What are main points/findings/debates concerning the priority area/sub-category allocated to you? 2. How does the information gathered in question 1 relate to the scope and the structure of the European Agenda on Migration? 3. What current information and data is available, who is producing it and how? 4. What and where are the main gaps and challenges? 5. What are the solutions or approaches to address these gaps and challenges based upon your research? To complement this review, two Annexes were created: the first being an overview of the main gaps and challenges as well as the suggested solutions for the whole report (Annex 1), and the second being a preliminary inventory of available migration data and data sources (Annex 2).JRC.E.6-Demography, Migration and Governanc

Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy.publishedVersio

Knowledge Management for Policy: Stocktaking of one year of JRC activities

Improving knowledge management and collaborative working is a priority for overcoming silos mentalities and connecting synergies between portfolios, as envisaged in the Commission Communication C(2016)6626. In its 2030 Strategy, the JRC took up this challenge by 1) introducing a horizontal ‘knowledge management’ layer in the organigram, to mobilise scientific competences from different Directorates around the Commission’s policy goals 2) championing the implementation of new collaboration practices and platforms as well as the development of a knowledge management professionalisation programme; 3) starting to transform itself from a traditional research-producing organisation into a world-leading manager of knowledge for EU policy-making. One year after the reorganisation carried out on the 1st of July 2016 to align the JRC organigram with the new strategy, this report reviews the progress made and describes the main achievements.JRC.H-Knowledge Management (Ispra

Relevance of cyclin D1b expression and CCND1 polymorphism in the pathogenesis of multiple myeloma and mantle cell lymphoma

BACKGROUND: The CCND1 gene generates two mRNAs (cyclin D1a and D1b) through an alternative splicing at the site of a common A/G polymorphism. Cyclin D1a and b proteins differ in their C-terminus, a region involved in protein degradation and sub-cellular localization. Recent data have suggested that cyclin D1b could be a nuclear oncogene. The presence of cyclin D1b mRNA and protein has been studied in two hemopathies in which cyclin D1 could be present: multiple myeloma (MM) and mantle cell lymphoma (MCL). The A/G polymorphism of CCND1 has also been verified in a series of patients. METHODS: The expression of cyclin D1 mRNA isoforms has been studied by real-time quantitative PCR; protein isoforms expression, localization and degradation by western blotting. The CCND1 polymorphism was analyzed after sequencing genomic DNA. RESULTS: Cyclin D1 mRNA isoforms a and b were expressed in mantle cell lymphoma (MCL) and multiple myeloma (MM). Cyclin D1b proteins were present in MCL, rarely in MM. Importantly, both protein isoforms localized the nuclear and cytoplasmic compartments. They displayed the same short half-life. Thus, the two properties of cyclin D1b recognized as necessary for its transforming activity are missing in MCL. Moreover, CCND1 polymorphism at the exon/intron boundary had no influence on splicing regulation in MCL cells. CONCLUSION: Our results support the notion that cyclin D1b is not crucial for the pathogenesis of MCL and MM

Clear Improvement in Real-World Chronic Myeloid Leukemia Survival: A Comparison With Randomized Controlled Trials.

Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15-64 years) diagnosed in 2000-2006 vs. 2007-2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there