26 research outputs found

    Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine in patients with advanced-stage, classical Hodgkin lymphoma: a prespecified subgroup analysis of high-risk patients from the ECHELON-1 study

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    Approximately one‐third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high‐risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON‐1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first‐line therapy after a median follow‐up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4-7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537-0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4-7 (HR, 0.588; 95% CI, 0.386-0.894; p = 0.012). The most common adverse events (AEs) in A + AVD‐treated versus ABVD‐treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4-7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high‐risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON‐1 shows a favorable benefit‐risk balance in high‐risk patients

    The transcription factor DBP affects circadian sleep consolidation and rhythmic EEG activity

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    Albumin D-binding protein (DBP) is a PAR leucine zipper transcription factor that is expressed according to a robust circadian rhythm in the suprachiasmatic nuclei, harboring the circadian master clock, and in most peripheral tissues. Mice lacking DBP display a shorter circadian period in locomotor activity and are less active. Thus, although DBP is not essential for circadian rhythm generation, it does modulate important clock outputs. We studied the role of DBP in the circadian and homeostatic aspects of sleep regulation by comparing DBP deficient mice (dbp-/-) with their isogenic controls (dbp+/+) under light-dark (LD) and constant-dark (DD) baseline conditions, as well as after sleep loss. Whereas total sleep duration was similar in both genotypes, the amplitude of the circadian modulation of sleep time, as well as the consolidation of sleep episodes, was reduced in dbp-/- under both LD and DD conditions. Quantitative EEG analysis demonstrated a marked reduction in the amplitude of the sleep-wake-dependent changes in slow-wave sleep delta power and an increase in hippocampal theta peak frequency in dbp-/- mice. The sleep deprivation-induced compensatory rebound of EEG delta power was similar in both genotypes. In contrast, the rebound in paradoxical sleep was significant in dbp+/+ mice only. It is concluded that the transcriptional regulatory protein DBP modulates circadian and homeostatic aspects of sleep regulation

    Atypical meningeal localization of classical hairy cell leukemia with an impressive response to rituximab and cladribine association. A case report and literature review

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    Abstract Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder classically presenting with cytopenia and recurrent infections but atypical manifestations such as bone lesions, skin lesions and effusion have been described. We report here an unusual meningeal localization in a 33 years old man who presented with headache, hand paresthesia and visual symptoms. Brain magnetic resonance imaging revealed an occipital meningeal lesion. Diagnostic explorations led to the diagnosis of classical HCL with meningeal localization. After treatment by cladribine and rituximab the patient rapidly improved and is still in complete remission 12 months after end of treatment. The literature review identified 9 other cases of HCL with central nervous system localization (CNS) presenting with brain parenchyma and/or meninges localization. Four out of 9 patients presented with hyperleukocytosis. Most patients experienced good responses with various treatments. Cladribine alone or with rituximab led to complete responses similar to our patient. In our patient, molecular biology revealed KLF2 mutations, which implication in the atypical localization could be suspected but would need dedicated studies. In conclusion, CNS localizations of HCL are rare but can be observed and treatment with cladribine alone or with rituximab appears as an effective strategy

    Influence of internal and outdoor factors on filamentous fungal flora in hematology wards.

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    International audienceBACKGROUND: Nosocomial invasive filamentous fungi infections could result from inhalation of filamentous fungi conidia present in hospital environment. METHODS: The environmental fungal flora in 3 different hospital wards with similar air conditioning was prospectively studied during 30 months and compared to internal (presence of agranulocytosis patient, behavioral practices, activity, cleaning work) and outdoor factors (meteorologic data, outdoor fungi). The general preventive measures differed from one unit to another. RESULTS: The hematology wards with filamentous fungi preventive measures were significantly less contaminated than a conventional ward without specific measures. Internal and outdoor factors influenced the level of fungal flora. However, the influence of internal factors was greater in the conventional ward than in hematology wards. The variation of flora in the hospital environment was seasonal, and the level of this contamination in each ward was influenced by the meteorology. However, outdoor factors more readily explain the variations of fungal load in hematology than in the conventional ward. CONCLUSION: This study highlights that specific preventive measures participate significantly in the control of the filamentous fungal flora intensity due to internal factors but not those due to outdoor factors, stressing the importance of high-efficiency particulate air filtration in high-risk units
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