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Summary Background Most patients with chronic lymphocytic leukaemia relapse after initial therapy combining chemotherapy with rituximab. We assessed the efficacy and safety of rituximab maintenance treatment versus observation for elderly patients in remission after front-line abbreviated induction by fludarabine, cyclophosphamide, and rituximab (FCR). Methods This randomised, open-label, multicentre phase 3 trial at 89 centres in France enrolled treatment-naive and fit patients aged 65 years or older with chronic lymphocytic leukaemia without del(17p). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0–1 and adequate renal and hepatic function. Patients in response to complete induction treatment with four monthly courses of full-dose FCR with two interim rituximab doses on day 14 of cycles 1 and 2 (oral fludarabine [40 mg/m 2 per day] and oral cyclophosphamide [250 mg/m 2 per day] for the first 3 days of each cycle, rituximab at 375 mg/m 2 intravenously on day 0 of cycle 1 and subsequently at 500 mg/m 2 on day 14 of cycle 1, days 1 and 14 of cycle 2, and day 1 of cycles 3 and 4) were eligible for randomisation. Recovery from FCR toxicity and patient willingness to continue the trial were mandatory. We randomly assigned (1:1) patients to either receive intravenous rituximab (500 mg/m 2 ) every 8 weeks for up to 2 years or undergo observation, with a central computer-generated randomisation list using randomly permuted blocks of variable sizes. Randomisation was stratified by IGHV mutational status, the presence or absence of del(11q), and response level to induction treatment. The primary endpoint was progression-free survival, with the objective to assess the superiority of rituximab maintenance relative to observation. The final analysis was done in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug in the rituximab group and in all patients in the observation group. This trial is closed to accrual whilst continuing patient follow-up. The study is registered with ClinicalTrials.gov, number NCT00645606. Findings Between Dec 14, 2007, and Feb 18, 2014, 542 patients were enrolled, of whom 525 started FCR induction. Between June 10, 2008, and Aug 14, 2014, 409 (78%) patients were randomly assigned to rituximab maintenance (n=202) or observation (n=207). Four (2%) patients in the rituximab group did not receive the allocated treatment (progressive disease [n=1], adverse events [n=3]). After a median follow-up of 47·7 months (IQR 30·4–65·8), median progression-free survival in the rituximab group (59·3 months, 95% CI 49·6–not estimable) was improved compared with the observation group (49·0 months, 39·9–60·5; hazard ratio 0·55, 95% CI 0·40–0·75; p=0·0002). Neutropenia and grade 3–4 infections were more common with rituximab maintenance (105 [53%] of 198 patients vs 74 [36%] of 207 patients and 38 [19%] vs 21 [10%], respectively) during the study. The most common grade 3–4 infection was lower respiratory tract infection (24 [12%] vs eight [4%]). The incidence of second cancers, except basal cell carcinoma, was similar in both groups (29 [15%] vs 23 [11%]). Deaths were related to adverse events for 23 (11%) patients in the rituximab group and 16 (8%) in the observation group. Interpretation 2-year maintenance rituximab in selected elderly patients improves progression-free survival and shows an acceptable safety profile. Immunotherapy maintenance strategy is a relevant option in front-line treatment of chronic lymphocytic leukaemia, even in the age of targeted therapy. Funding French National Cancer Institute (INCa), Roche, Chugai.

Introduction Peu d’options therapeutiques sont disponibles chez les patients (pts) atteints de carcinome epidermoide (CE) evolue. Le cemiplimab, un anti PD-1, apporte des reponses prolongees chez 47 % des pts dans un essai de phases I–II recemment publie. CARSKIN est le 1er essai ouvert de phase II evaluant le pembrolizumab (PBZ) chez des patients atteints de CEC inoperable. Nous presentons les resultats d’efficacite et de tolerance de la 1re etape de CARSKIN. Patients et methodes Les pts ayant un CE inoperable, un PS ECOG Resultats Dix-neuf pts, d’âge median 80 ans (61–88), majoritairement des hommes (79 %) ayant des metastases locales (n = 7), regionales (n = 7) ou a distance (n = 6) etaient inclus entre mars et juillet 2017. Le PS etait de 0 chez 39 % des pts. L’expression de PD-L1 a la baseline etait > 1 % dans 10 cas (53 %). Le nombre median de perfusions de PBZ etait de 9 (0–13). Le suivi median etait de 7 mois. En intention de traiter, le taux de reponse a S15 etait de 42 % (IC a 95 % : 23–63 %) correspondant a 7 RP et 1 RC confirmees. Le taux de controle de la maladie a S15 etait de 58 % (11/19 dont 3 stabilisations). Seul 1 repondeur a progresse pendant le suivi. La mediane de survie sans progression etait de 7 mois et la mediane de survie globale n’est pas encore atteinte. L’expression mediane de PD-L1 (Q1–Q3) etait de 28 % (1–75 %) chez les repondeurs vs 0 % (0–3 %) chez les non-repondeurs a S15 (p = 0,15). Il n’y a pas eu de deces ni d’EIG lie au PBZ. Un patient a arrete le PBZ suite a une colite de grade 2. Des EI lies au PBZ sont survenus chez 63 % des patients dont les plus frequents etaient fatigue (42 %), eruptions cutanees (32 %), prurit (16 %), dysthyroidie (16 %) et diarrhee (10 %). Conclusion Le PBZ en 1re ligne et en monotherapie chez les pts atteints de CE inoperable montre une activite clinique encourageante caracterisee par un taux de reponse eleve et des reponses durables. La tolerance etait bonne chez ces pts âges. Les inclusions de la 2nde etape de CARSKIN sont achevees.

Ochrobactrum anthropi is an oxidase-producing gram-negative bacillus preferring aqueous environments. It is an opportunist of low pathogenicity with a wide and unpredictable antibiotic resistance. We observed bacteraemia caused by this organism in two immunocompromized patients hospitalized in the same haematology unit and catheter-associated sepsis was recognized within two days. Another isolate was obtained from the stools of a third patient of the same unit. Environmental investigations recovered an isolate from a tap-water sample of the unit. Pulsed-field gel electrophoresis analysis of these four isolates and two others isolates previously found in the same ward, showed identical restriction patterns for the two blood isolates and confirmed that the two bacteraemia were epidemiologically related.

Acquired methemoglobinemia is a rare but severe condition associated with oxidizing stressors, most notably medications. Although the symptoms can be life threatening, they usually respond promptly to exposure cessation and methylene blue injection. We describe the first case of methemoglobinemia associated with tetracaine lozenge use. A previously healthy 33-year-old man was admitted with fever, respiratory distress, cyanosis, and acute hemolysis. Physical findings and chest radiograph were normal. Low pulse oximetry readings contrasted with normal partial pressure of oxygen and calculated oxygen saturation. The methemoglobin level was 10.8%. The patient recovered with methylene blue injection and blood transfusions. He reported recent self-medication with tetracaine lozenges for a sore throat during a flu-like illness. No other cause of methemoglobinemia was found.

Resume Ces 15 dernieres annees, differentes methodes de detection et de diagnostic rapide de mycobacteries ont ete developpees afin de diminuer les delais de l'identification generalement realisee en deux etapes (obtention d'une primoculture a partir du prelevement pathologique puis identification d'une subculture selon des caracteres physiologiques et biochimiques). Certaines de ces methodes comme l'amplification genique in vitro (PCR), la chromatographie gazeuse liee a la spectrometrie de masse, la detection d'antigenes specifiques sont directement applicables aux echantillons cliniques; d'autres comme la methode radiometrique ou l'utilisation de milieu biphasique permettent l'obtention plus rapide de primocultures; d'autres enfin par la detection de glycolipides ou d'acides gras (en particulier des acides mycoliques), ou l'utilisation de sondes nucleiques autorisent l'identification rapide des primocultures. Toutes ces methodes sont comparees quant a leur sensibilite, specificite, facilite de mise en oeuvre et de realisation ainsi que leur cout. L'adoption d'une ou plusieurs de ces methodes rend desormais possible la mise au point de nouvelles strategies d'identification, ce qui aura pour consequence une reorganisation interne generale des laboratoires ainsi qu'une modification profonde de leurs reseaux de collaboration.

Resume L'ubiquite des mycobacteries dans l'environnement, leurs formidables capacites d'adaptation font de ces germes des compagnons obligatoires de l'homme. Les contacts frequents peuvent entrainer des problemes de diagnostic faussement positifs que le bacteriologiste se doit de resoudre. Il appartient aux laboratoires cliniques de surveiller avec attention les augmentations de taux d'isolement de mycobacteries atypiques, de maniere a deceler rapidement les pseudo-epidemies. De plus les mycobacteries sont capables de coloniser les voies aeriennes superieures, le tractus digestif et la peau. La colonisation des individus, eventuellement decelee par des reactions d'hypersensibilite, peut etre a l'origine d'infections, en particulier chez des sujets immunodeprimes. La distinction entre colonisation et infection ne peut s'effectuer qu'a la lumiere d'arguments cliniques, radiologiques ou anatomo-pathologiques. De plus la resistance des mycobacteries aux desinfections usuelles et donc leur persistance dans du materiel ou des produits supposes steriles peut occasionner des infections nosocomiales. Une attention toute particuliere doit etre apportee a la sterilisation, en particulier de l'eau et des solutions aqueuses, lors de tout acte medical ou chirurgical meme benin afin de prevenir de possibles infections dues aux mycobacteries de l'environnement.

Summary A 49 year old man was medically treated, first in 1986 and then in 1988, for atypical primary pulmonary infection caused by Mycobacterium malmoense. Since no clinical or bacteriological improvement of both smear and culture was observed, upper right bilobectomy was performed in december 1988. Oral treatment with rifabutin, clofazimine, ethambutol and isoniazid was clinically and bacteriologically successful in May 1989. In 1990, Aspergillus flavus infection developed in a sequeleae cavity located in the posterior segment of the upper left lobe. To our knowledge the Mycobacterium malmoense-Aspergillus flavus association has not yet been described.

Objective To propose and compare practical approaches that allow eliciting and using expert opinions about the benefit effect on a censored endpoint, such as event-free survival (EFS), used in the planning of a clinical trial based on Bayesian methodology. Study Design and Setting Individual interviews of 37 experts. Bayesian normal models on the log hazard ratio (HR) of EFS were implemented. We illustrate our approach by using a trial of autologous stem cell transplantation (ASCT) vs. chemotherapy (CT) in chronic lymphocytic leukemia (CLL). We elicited experts' prior beliefs about the difference in 3-year EFS between the two treatment arms, either roughly or throughout weights over the difference scale. Subsequently, a Bayesian synthesis of the information reported in the trial protocol with that in the experts' prior was performed, using: (1) the postulated treatment effect based on null (skeptical) and alternative (enthusiastic) hypotheses with shared standard error; and (2) the expected difference derived from experts' distributions. Results As compared with the priors based on the trial protocol data, expert priors agreed with some average from enthusiastic and skeptical information, with close standard errors. Conclusion This case study illustrates a rational approach to construct an expert-based prior. It should be considered as part of the design of future Bayesian trials.