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Due to the low number of bacteraemias identified after the first day of fever, repeating blood cultures adds little additional information while potentially increasing iatrogenesis, costs, and the number of false positive blood cultures. Repeat blood cultures in children with persistent fever and neutropenia: diagnostic and clinical implications: repeat blood cultures for fever and neutropenia. The new blood culture sample strategy - four adequately filled blood culture bottles on day 1 - efficiently improved the diagnosis of bacteriemia over the three periods. [Extracted from the article]

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is part of the treatment strategy for some patients with high-risk lymphoma by improving survival with an acceptable toxicity profile. Although the BEAM (BCNU, etoposide, cytarabine, and melphalan) intensification regimen is the most used, the optimal dosing for each drug is unclear. Here, we retrospectively compared the outcome of 110 patients receiving higher (400 mg/m2, n = 69) or lower (200 mg/m2, n = 41) etoposide and cytarabine doses in our institution between 2012 and 2019. Patients in the BEAM 200 group experienced less toxicity with reduced fever duration (P < 0.001), number of platelet transfusions (P = 0.008), antibiotic duration (P < 0.001), antifungal therapy (P < 0.001), and mucositis (P < 0.001) whereas length of stay, admission to the intensive care unit, and in-hospital mortality were not different between groups. Progression-free survival (PFS) was non-significantly lower in the BEAM 200 group (36-month PFS, 68% vs. 80%, P = 0.053) whereas OS was similar between the two groups (36-month OS, 87% vs. 91%, respectively, P = 0.12). Albeit a non-significant reduction in PFS, BEAM 200 conditioning intensity was associated with a reduced toxicity profile. [ABSTRACT FROM AUTHOR]

Background: Recently, the combination of venetoclax plus a hypomethylating agent (HMA; azacitidine ordecitabine) or low‐dose cytarabine (LDAC) showed promise in Phase III trials in previously untreated AML. In France at the time of this study, venetoclax was not yet approved for AML and there were therefore no formal usage recommendations. Here we report the first study in a French cohort that assessed venetoclax in combination with existing treatments for AML under real‐life conditions. Method: This retrospective, real‐life study collected data on venetoclax use and management in a French cohort with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Result: Of 118 patients, 81 were in second line/beyond (71.6% also hypomethylating agent [HMA]; 23.5% lowdose cytarabine [LDAC]) and 37 in first line. For venetoclax initiation, 57.3% underwent ramp up and 74.6% were hospitalized. Median venetoclax duration was 2.5 months (range 0.03‐16.2). With all treatment lines and regimens, most common grade 3/4 adverse events were hematologic (overall 96.4% of patients) and infections (57.1%). Dosage adjustments for drug interactions and safety varied between centers. In second‐line/beyond, median progression‐free survival was 4.0 months (95% confidence interval [CI] 2.7‐12.8) with venetoclax‐HMA and 3.4 months (1.3‐8.9) with venetoclax‐LDAC; overall response rate was 51.9% and 41.2%, respectively. Thus, we showed that venetoclax‐based treatment yields promising findings in patients with AML, but to address treatment complexity, practice harmonization is needed. [ABSTRACT FROM AUTHOR]

Daunorubicin pharmacokinetics (PK) are characterised by an important inter-individual variability, which raises questions about the optimal dose regimen in patients with acute myeloid leukaemia. The aim of the study is to assess the joint daunorubicin/daunorubicinol PK profile and to define an optimal population PK study design. Fourteen patients were enrolled in the PK ancillary study of the BIG-1 trial and 6–8 samples were taken up to 24 h after administration of the first dose of daunorubicin (90 mg/m2/day). Daunorubicin and daunorubicinol quantifications were assessed using a validated liquid chromatography technique coupled with a fluorescence detector method. Data were analysed using a non-compartmental approach and non-linear mixed effects modelling. Optimal sampling strategy was proposed using the R function PFIM. The median daunorubicin and daunorubicinol AUC0-tlast were 577 ng/mL·hr (Range: 375–1167) and 2200 ng/mL·hr (range: 933–4683), respectively. The median metabolic ratio was 0.32 (range: 0.1–0.44). Daunorubicin PK was best described by a three-compartment parent, two-compartment metabolite model, with a double first-order transformation of daunorubicin to metabolite. Body surface area and plasma creatinine had a significant impact on the daunorubicin and daunorubicinol PK. A practical optimal population design has been derived from this model with five sampling times per subject (0.5, 0.75, 2, 9, 24 h) and this can be used for a future population PK study. [ABSTRACT FROM AUTHOR]

Summary: We analysed long‐term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo‐HSCT) as a first transplant for high‐risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo‐HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T‐cell/depleted grafts (TCD). The 100‐day cumulative incidence (CI) of grade II‐IV acute graft‐versus‐host disease (GVHD) was 25% and the 3‐year CI of chronic GVHD was 38%. The 3‐year CI of non‐relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow‐up of 58 months, 3‐year overall survival (OS) and progression‐free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced‐intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high‐risk HL and candidates of allo‐HSCT, a MAC strategy with TCD might be the best option. [ABSTRACT FROM AUTHOR]

Background: Three different scoring systems have been developed to assess pre‐transplant comorbidity in allogeneic hematopoietic stem cell transplantation (Allo‐HSCT): the Hematopoietic Cell Transplantation‐Specific Comorbidity Index, the Comorbidity/Age index, and the Augmented Comorbidity/Age index. All were devised to predict overall survival (OS) and disease‐free survival (DFS) survivals and non‐relapse mortality (NRM) in patients receiving HLA‐matched Allo‐HSCT, but their performance has scarcely been studied in the haploidentical Allo‐HSCT setting with post‐transplant cyclophosphamide, a procedure in constant expansion worldwide. Methods: To address this issue, their impact on survivals and NRM was examined in a cohort of 223 patients treated with haploidentical Allo‐HSCT in four different centers. Results: With a median follow‐up of 35.6 months, 3‐year OS, DFS, and NRM were 48.1% ± 4%, 46.3% ± 4%, and 30.0% ± 3%, respectively. No impact was found for any of the three comorbidity scores in univariate analysis. In multivariate analyses, the only three factors associated with lower OS were DRI (p < 0.001), an older age of recipients (≥55 years old, p = 0.02) and of donors (≥40 years old, p = 0.005). Older donor age was also associated with lower DFS and higher NRM. Conclusion: The comorbidity scores do not predict survivals nor NRM in haploidentical Allo‐HSCT with PTCY, suggesting that pre‐transplant comorbidities should not be a contra‐indication to this procedure. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo‐HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo‐HSCT. Methods: We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically. Results: Average gamma globulin levels between D‐7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P =.65). Gamma globulin level <400 mg/dl was not associated with the occurrence of infection between the test studied and the next one (aOR 1.33 [0.84‐2.15], P =.24). The gamma globulin level was not predictive of bacterial or fungal infections (AUC 0.54 [95%CI: 0.47‐0.61]) nor of viral reactivations (AUC 0.51 [95%CI: 0.43‐0.60]). Conclusions: This confirmed that the humoral deficiency is a minor part of the immune deficiency in the 100 days post‐transplant. This questions the relevance of the indications of immunoglobulin substitution during this period. [ABSTRACT FROM AUTHOR]

Background: Graft Versus Host Disease (GvHD) is a frequent complication of hematopoietic stem cell transplantation (HSCT). Acute GvHD can involve intestinal tract which requires temporary fasting in addition to immunosuppressive treatment. Surgical management of gastrointestinal (GI) GVHD is an unusual approach. Objectives: Diversion stoma can help in healing the digestive tract during the acute phase of GI GvHD by keeping it free from any aggression. We report our experience of 6 adult patients with Gl GvHD who underwent intestinal surgery. Study Design: Medical files of patients who experienced biopsy-proven GI GvHD between 01/01/2011 and 31/12/2019 in Angers University hospital were retrospectively reviewed and patients who underwent GI surgery were analysed. Informed consent was obtained from all patients. Results: Between 2011 and 2019, 354 allogenic HSCT were performed and stage II to IV acute GI GvHD occurred in 42 patients. GI surgery and diversion stomas were required for 6 patients. Two surgeries were performed urgently for colonic perforation, 2 were performed for small bowel occlusion symptoms and 2 for uncontrolled GvHD symptoms despite medical treatment. All surgeries were performed safely. Diversion stomy could not prevent aGvHD progression and death in 2 patients. Additional treatment for GI GvHD was necessary in 1 patient while 3 patients did not receive any further treatment for GI GvHD after long-term follow-up. Two patients had successful bowel continuity restoration. Data from 29 patients who underwent GI surgery for acute GVH published so far are reviewed. Conclusion: GI surgical interventions are rarely required in patients with GI GvHD. There is a lack of data on digestive surgery in GI GVHD, including follow-up data and efficiency on GVHD-related symptoms. The use of digestive surgery as diversion stoma appeared feasible for severe GI GVHD and seems to benefit some patients. This data should be confirmed in a larger study. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the level of knowledge of Middle East respiratory syndrome coronavirus (MERS-CoV) among Hajj pilgrims before and after an education health programme during international vaccine consultations in France. A cross-sectional study was performed in the consultation for travel medicine and international vaccination in Reims University Hospital between July 2014 and October 2015. Consecutive adults (>18 years old) who attended for pre-Hajj meningococcal vaccination were eligible to complete an anonymous questionnaire with closed answers to evaluate their level of knowledge about MERS-CoV. To evaluate the effectiveness of the information given during the consultation, the same questionnaire was completed by the Hajj pilgrim before and after the consultation, where the information about MERS-CoV was provided. Among 82 Hajj pilgrim adults enrolled in the study, less than 25% were aware of the routes of transmission, symptoms and preventive behaviours to adopt abroad or in case of fever. Pilgrims had a higher rate of correct responses on each question at the time they completed the second questionnaire, as compared with the first, with 11 of 13 questions answered significantly better after delivery of educational information about MERS-CoV. However, although the rate of correct answers to the questions about routes of transmission, symptoms, preventive behaviours to adopt in case of fever and time delay between return and potential MERS-CoV occurrence increased significantly after receiving the information, the rates remained below 50%. Information given during travel consultations significantly increases the general level of knowledge, but not enough to achieve epidemic control. • Information targeting the public is the preferred means to implement infection control. • The level of knowledge about MERS-CoV among Hajj pilgrims significantly increases before and after an educational health program. • However, knowledge about certain preventive behaviours remained insufficient and was not enough to achieve epidemic. [ABSTRACT FROM AUTHOR]

Résumé Introduction Nous avons tenté d’apprécier (i) la fréquence des consultations pour malaise au service d’accueil des urgences (SAU) d’un centre hospitalier universitaire (CHU), (ii) l’épidémiologie clinique, et (iii) le coût des malaises, en s’intéressant aux facteurs associés à l’hospitalisation. Méthodes Cette étude rétrospective a été menée à partir des données des patients ayant consulté pour « malaise » au SAU du CHU de Reims, (01/01/12–31/03/12). Tous les dossiers ont été reclassés en syncope/lipothymie/perte de connaissance brève, d’une part, et en syncope selon la définition anglo-saxonne reprise par la Haute Autorité de santé (HAS), d’autre part. Résultats Trois cent quarante et un patients parmi les 5953 patients de la période de l’étude (5,7 %) ont consulté pour malaise. Les données de 296 patients ont été analysées. Cette population comportait 62,8 % de femmes, avec un âge médian de 43 ans. L’examen clinique était normal dans 57 % des cas. Il s’agissait de lipothymies sans perte de connaissance complète, non prises en compte dans la classification HAS dans 48 % des cas. Les patients restaient une durée médiane de 4 heures au SAU et 67 patients (22,6 %) ont été hospitalisés. Le coût minimal a été estimé à 280 000 euros. Les facteurs de risque associés à une hospitalisation étaient un âge ≥ 60 ans ou la présence d’une perte de connaissance complète, à l’inverse de la présence de circonstances favorisant l’hypertonie vagale. Conclusion Un âge ≥ 60 ans et/ou la présence d’une perte de connaissance complète semblent associés à l’hospitalisation. Introduction We assessed (i) the frequency of consultations for faintness in the Emergency department (ED) of a University hospital centre (UHC), (ii) clinical epidemiology and (iii) cost of faintness, taking a particular interest into the determining risk factors for hospitalization. Methods This epidemiological study has been conducted retrospectively, from data obtained for every patient having consulted for faintness in ED of Reims UHC (01/01/12–03/31/12). Every medical record was classified as syncope/lipothymia/brief consciousness loss on one hand and as syncope according to the definition of the French Health High Authority (FHHA). Results Three hundred and forty-one patients out of 5953 (5.7%) were referred for faintness during the study period. Medical records were analysed for 296 patients. Sixty-two point eight percent were women, with a median age of 43 years. Physical examination was normal for 57% of patients. For 48% of cases, there was no complete consciousness loss thus corresponding to lipothymia, which is not taken into account by the FHHA definition. Median length of stay in the ED was 4 hours and 67 patients (22.6%) were hospitalized. Minimal estimated cost was 280,000 euros. Risk factors independently associated with hospitalization were age ≥ 60 and complete consciousness loss unlike predisposing circumstances to vagal hypertonia. Conclusion Age ≥ 60 and complete consciousness loss seemed to be associated with hospitalization. [ABSTRACT FROM AUTHOR]

L'ibrutinib, inhibiteur irréversible et non spécifique de la Bruton tyrosine kinase (BTK), voie du BCR, est utilisé dans le traitement de nombreuses hémopathies lymphoïdes B. L'ibrutinib forme un lien covalent robuste avec la BTK et inhibe les voies de survie et multiplication cellulaires, empêchant les cellules lymphomateuses d'adhérer aux ganglions lymphatiques, environnement qui leur est favorable. Le traitement entraîne une mort cellulaire lors de leur migration dans le sang, environnement qui ne leur est pas favorable. Parmi les effets indésirables connus (cytopénies, troubles digestifs, fibrillation auriculaire, thrombopathies...), on retrouve des complications infectieuses essentiellement bactériennes, des voies respiratoires et urinaires. Concernant les atteintes cutanées, sont décrit principalement des rashs, un cas de panniculite et un cas d'abcès cutanés multiples à Fusarium spp [1]. Nous rapportons le cas d'un homme de 71 ans, diabétique de type 2, traité par ibrutinib depuis juillet 2015 en 2e ligne d'une maladie de Waldenström. Un traitement antérieur par 6 cures de rituximab–cyclophosphamide–dexaméthasone avait été initié devant des cytopénies sévères (Hb à 4,8 g/L) sans syndrome tumoral associé, avec un échec primaire ayant conduit à l'introduction de l'ibrutinib. En mars 2017, il développe un premier abcès cutané en fosse iliaque gauche nécessitant une mise à plat chirurgicale. Aucune documentation microbiologique n'est retrouvée. En juillet 2017, alors que le patient est toujours traité par ibrutinib, et présente une hypogammaglobulinémie à 5,9 g/L (et un pic IgM à 0,6 g/L) et une lymphopénie à 0,7 G/L, sans autre lésion cutanée, survenue d'un nouvel abcès spontané paralombaire droit à Staphylococcus aureus meti sensible nécessitant une mise a plat chirurgicale de la collection inguinale gauche précédemment opérée, et de l'abcès paralombaire droit. La recherche du portage de la leucocydine de Panton-Valentine s'avère négative. Devant l'absence d'autre étiologie, outre le diabète favorisant la susceptibilité aux infections, le traitement par ibrutinib est arrêté en juillet 2017. L'évolution a été partiellement favorable sous antibiothérapie, mise en place d'un VAC et soins quotidiens, avec retard de cicatrisation de l'abcès inguinal gauche. Depuis son arrêt, il n'y a pas eu de nouvelle infection, pas de cytopénie, le pic est à 1,2 g/L. Nous rapportons, via cette observation, le premier cas d'abcès récidivants à S. aureus survenant au cours du traitement par ibrutinib. Le traitement peut être responsable de complications infectieuses via une diminution de la phagocytose par les macrophages, du chimiotactisme, de l'adhésion et la migration des PNN, la sécrétion de cytokines pro-inflammatoires et la migration des cellules épithéliales vers le site infectieux. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective study, we analyzed the impact of adding high-dose methotrexate to standard chemotherapy on the outcome of patients with diffuse large B-cell lymphoma and skeletal involvement. Our results suggest improved outcome in those who received high-dose methotrexate which should be confirmed in prospective controlled studies. Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials. [ABSTRACT FROM AUTHOR]

Delayed onset haemolysis occurring post-artesunate and post-artemisinin combination therapy is secondary to delayed clearance of infected erythrocytes spared by pitting during treatment. We report a case of severe post-treatment delayed haemolytic anaemia with a positive direct antiglobulin test and a positive response to corticosteroid therapy, suggesting an associated immune mechanism. [ABSTRACT FROM AUTHOR]

Introduction L’idelalisib est le premier médicament d’une nouvelle classe de thérapie ciblée. Il s’agit d’un inhibiteur des PI3 kinase, indiqué en association avec le rituximab dans le traitement de patients atteints de leucémie lymphoïde chronique et de lymphome folliculaire. Des pneumopathies sévères ont été décrites au cours d’essais thérapeutiques avec une surmortalité dans le bras idelalisib. Matériels et méthodes Nous rapportons une série de 5 cas de pneumopathies sévères parmi les 16 patients (31 %) ayant initié l’idelalisib entre septembre 2014 et novembre 2015 dans notre centre. Résultats Le délai médian était de 1 mois (extrêmes, 1–11). Un patient a présenté une pneumopathie à P . jiroveci et 1 patient une pneumopathie au décours d’une neutropénie sévère. Dans les 3 autres cas, aucune étiologie infectieuse n’a pu être mise en évidence malgré un bilan exhaustif (lavage broncho-alvéolaire). Dans ces cas, l’arrêt de l’idelalisib et la corticothérapie a été suivi d’une évolution favorable. Les pneumopathies sous idelalisib peuvent être secondaires à des pneumonies infectieuses ou à une toxicité pulmonaire médicamenteuse. La physiopathogénie de cette toxicité n’est pas connue mais s’apparente à celle déjà décrite avec les inhibiteurs de mTOR ; l’idelalisib en inhibant PI3Kδ inhibe aussi la voie des mTOR. Conclusion Les infectiologues ne doivent pas méconnaître la toxicité médicamenteuse pulmonaire dans l’approche diagnostique d’une pneumopathie survenant chez un patient traité par idélalisib. [ABSTRACT FROM AUTHOR]

The article discusses the study which investigates the level of knowledge of French travellers about the risk multidrug-resistant Enterobacteriaceae (MRE). The study involves a total of 191 French adult travellers who attended a consultation for travel medicine and found that 10% of them were aware of the MRE's risk during travel. The study suggests the benefits provided by consultation on travel medicine.