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Introduction La leucemie chronique a eosinophiles associeeau transcrit FIP1L1-PDGFRA (LCE F/P) est un syndrome hypereosinophilique(SHE) clonal qui presente une grande sensibilite al’Imatinib Mesylate (IM) et dont l’incidence n’est pas connue. Les series publiees a ce jour sont de petite taille, avec un suivi limite et bien que les caracteristiques cliniques ainsi que la possibilite d’arret de l’IM soient connues, aucun facteur predictif de rechute n’a ete mis en evidence. Patients et methodes Etude francaise, multicentrique, retrospective en partenariat avec le groupe des biologistes moleculaires des hemopathies malignes incluant l’ensemble des patients ayant eu une recherche de F/P positive entre 2003 et 2019. Les patients avec une hemopathie aigue ou des donnees cliniques manquantes ont ete exclus. Un modele de regression logistique a ete utilise pour identifier des facteurs de risque de rechute. Resultats Parmi les 197 transcrits F/P positifs, 151 patients ont ete inclus (97 % d’hommes, âge moyen 49 ans). L’incidence de la LCE F/P etait estimee a 0,18 cas par an par million d’habitants. Comme precedemment decrit, les organes les plus frequemment atteints etaient la rate (44 %), la peau (32 %), le poumon (30 %), le coeur (19 %) et le Systeme Nerveux Central (10 %). Par ailleurs, des atteintes vasculaires (thrombose, occlusion arterielle, vascularite), articulaire et renale ont egalement ete decrites. Le pic d’eosinophilie moyen etait de 10,3 (± 6) G/l et les taux de vitamine B12, de tryptase et d’IgE totales etaient eleves dans 74/79 (94 %), 45/57 (79 %) et 12/86 (14 %) des cas tandis qu’une elevation franche de la CRP (i.e. > 40 mg/l) n’etait retrouvee que chez 5 patients. Trente et un (20 %) patients ont ete traites par corticoides sans aucune remission complete tandis que tous les patients traites par IM (n = 148) ont eu une reponse hematologique et moleculaire (n = 84 tests) complete. Parmi les 46 patients ayant arrete l’IM, 20 (47 %) ont presente une rechute. En analyse multivariee, le delai d’introduction du traitement (HR continu : 1,02 [1,00–1,03] ; p = 0,01) et la duree du traitement (HR continu : 0,97 [0,95–0,99] ; p = 0,01) etait des facteurs associes a la rechute. La duree de suivi moyenne etait de 80 (± 56) mois avec une survie globale a 1, 5 et 10 ans de 99 %, 95 % et 84 % respectivement. Conclusion Cette etude avec un large effectif confirme la predominance masculine de cette pathologie ainsi que la frequence des atteintes respiratoire, cardiaque, cutanee et splenique. Apres arret de l’IM une courte duree de traitement prealable et un delais prolonge d’introduction de l’IM etaient associes a la rechute.

Background ULTIMATE, a phase III trial, showed a significant superiority regarding progression free survival (PFS) of the combination paclitaxel-bevacizumab versus docetaxel as second or third line treatment for advanced non-small cell lung cancer (NSCLC). With the increase use of immunotherapy in first-line setting, second line strategies must be redefined. Paclitaxel-bevacizumab combination could be an option. Methods The main objectives were to describe safety and efficacy of this combination in metastatic non-squamous NSCLC as second-line therapy or beyond with a special attention paid to the sub-group treated just after immune checkpoint inhibitors. It was a multicentric retrospective study. Results This analysis included from 1st September 2010 to 1st april 2018, 76 patients: 42 (55%) male, 18 (24%) and 36 (47%) treated in second and third line respectively, and 22 (29%) in fourth line or more. Overall response rate (ORR) was 37% (28/76) and disease control rate 74 % (56/76). Median PFS and OS were 5,7 [95%CI: 4,1-6,9] months and 11,2 [95%CI: 8-not reached] months respectively. In second and third line, ORR was respectively 39% and 42%, PFS 4 months [95%CI: 2,5-7,7] and 6 months [95%CI: 4-7], OS 9,4 months [95%CI: 2,7-not reached] and was not reached in third line at 12 months. Grade 3–4 adverse events included asthenia 5% (4/76), neurotoxicity 3% (2/76), bleeding events 4% (3/76), and hematological toxicity 1% (1/76). In the subset of patients treated in third-line or beyond, immediately after immunotherapy (33/76), we note with interest that ORR was 42% (14/33), median PFS was 6,2 [95% CI: 4,6-7,7] months, and median overall survival was not reached at 12 months. Conclusion This study shows an acceptable toxicity profile associated with encouraging efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non –squamous NSCLC patients. Moreover, these results seems to be very promising preliminary findings for patients treated just after immunotherapy. AVATAX is ongoing and should collect data from about 200 patients. Legal entity responsible for the study Chantal Decroisette. Funding Has not received any funding. Disclosure C. Chouaid: Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AZ; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BI; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer and Amgen; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Takeda; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi Aventis; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: GSK. G. Rousseau-Bussac: Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): roche; Travel / Accommodation / Expenses: Bristol-Myers-Squibb, Travel / Accommodation / Expenses: Takeda; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Mundipharma; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Janssen-Cilag; Travel / Accommodation / Expenses: Boehringer Ingelheim. J. Pinsolle: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre Fabre. R. Descourt: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda. M. Geier: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb. C. Decroisette: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

Bisphosphonates are indicated for the treatment of bone lesions in patients with solid tumours or multiple myeloma. Bisphosphonates have proven their effectiveness in reducing the number of bone complications (hypercalcemia, pain, disease-related fractures, spinal cord compression) and delaying their occurrence in patients with bone tumours; they have also been shown to reduce the need for bone surgery and palliative or pain-relieving radiotherapy in these patients. International recommendations for the treatment of bone lesions related to malignant solid tumours and multiple myeloma have been established. We have elaborated clinical practice guidelines on the use of bisphosphonates to assist treatment decision-making in bone oncology. The guide contains decision trees and tables with information to guide pre-treatment evaluation and patient follow-up, as well as indications and conditions of use of bisphosphonates. In 2007, the regional cancer network of Rhone-Alpes, ONCORA, formed a working group (GIP ONCORA) to elaborate the guideline. The final version was then discussed and adopted at a plenary session in July 2009, during a collaborative workshop on supportive care recommendations organized by ONCORA and the regional cancer network of Lorraine.

The aim of this study was to describe a high-performance liquid chromatography (HPLC) assay for the determination of cefepime and cefpirome in human serum without changing chromatographic conditions. The assay consisted to measure cefepime and cefpirome which were unbound to proteins having a molecular mass of 10,000 or more by ultrafiltration followed by HPLC with a Supelcosil ABZ+ column and UV detection at a wavelength of 263 nm. The assay was been found to be linear and has been validated over the concentration range 200 to 0.50 microg/ml for both cefepime and cefpirome, from 200 microl serum, extracted. In future, the assay will support therapeutic drug monitoring for cefepime and cefpirome in neutropenic patients in correlation with microbiological parameters such as MIC90 (minimal inhibitory concentration of antibiotic which kills 90% of the initial bacterial inoculum) and clinical efficacy.

Resume Les hyperlymphocytoses CD8 avec neutropenie constituent un groupe heterogene au sein duquel sont rassembles des etats cliniques benins reactionnels et d'authentiques pathologies neoplasiques entrant dans le cadre des leucemies a grands lymphocytes granuleux. Le pronostic de ces leucemies a LGL (Large Granular Lymphocyte) semble lie au phenotype: extremement severe et rapidement lethal lorsque le phenotype est de type NK, chronique et lentement evolutif lorsque le phenotype est de type T (CD8+). Les auteurs rapportent quatre observations d'hyperlymphocytose CD8+ avec neutropenie, correspondant a des proliferations lymphocytaires CD2±, CD3+, CD4-, CD8+, CD16-, CD56±, CD57+, associees a un rearrangement clonal du gene b du recepteur T. Dans deux des quatre observations, l'hyperlymphocytose sanguine caracteristique n'est apparue qu'apres la splenectomie, mais l'analyse retrospective des biopsies osteo-medullaires permet d'affirmer la preexistence de la pathologie clonale. Ces lymphocytes ont une faible activite Natural Killer contre la lignee K562. Il n'y a pas de sequence provirale HTLV1 integree dans l'ADN de ces cellules leucemiques. L'evolution de cette pathologie monoclonale est cliniquement benigne, chronique, avec un recul de plus de treize ans dans un cas. Si la splenctomie n'a pas corrige la neutropenie, elle a permis le controle d'une anemie hemolytique et d'une thrombopenie de type peripherique chez un patient.

The syndrome of CD8+ hyperlymphocytosis with neutropenia is a heterogeneous disorder ranging from reactive begnin state to neoplasic pathology. We report four patients with CD8+ Large Granular Lymphocytes Leukemia which are CD2−, CD3+, CD4−, CD8+, CD16−, CD57+, with clonal rearrangement of T-cell receptor β gene.