Antilymphocyte globulin for matched sibling donor transplantation in patients with myelofibrosis

The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft-versus-host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n= 287). The cumulative incidences of grade II-IV acute graft-versus-host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft-versus-host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft-versus-host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P= 0.010) while it did not decrease the risk of chronic graft-versus-host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P-values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft-versus-host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft-versushost disease without increasing the risk of relapse.Peer reviewe

Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease : Final Results From the International Compassionate Use Program

Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable and potentially fatal complication of hematopoietic cell transplantation (HCT) or nontransplantation-associated chemotherapy/radiotherapy. In cases of severe hepatic VOD/SOS, typically defined by associated multiorgan failure (MOF, also known as multiorgan dysfunction), mortality exceeds 80%. Preclinical and early clinical data have provided a rationale for defibrotide treatment in hepatic VOD/SOS. Based on this evidence and in recognition of the dismal prognosis for these patients, defibrotide was made available through an international multicenter compassionate-use program conducted from December 1998 to March 2009. Physicians participating in the program voluntarily provided demographic and outcome data for patients given defibrotide. Efficacy and safety analyses were performed using the data received for 710 treated patients. Defibrotide was given at 10, 25, 40, 60, or 80 mg/kg/day for a median of 15 days (range, 1 to 119 days). By Kaplan-Meier analysis, the estimated overall day +100 survival was 54% (58% in the 25 mg/kg/day dose group). Adverse events (AEs) were reported in 53% of patients. The most common AEs were MOF, progression of hepatic VOD/SOS, sepsis, and graft-versus-host disease, which were consistent with the AEs expected for this patient population. No clinically meaningful trends in AEs were identified by gender, age, or dose group. Safety and efficacy results were consistent with prior studies of defibrotide in hepatic VOD/SOS, and subgroup analyses lend support to the use of the 25 mg/kg/day dose. (C) 2016 American Society for Blood and Marrow Transplantation.Peer reviewe

Durable response with single-agent acalabrutinib in patients with relapsed or refractory mantle cell lymphoma

Bruton tyrosine kinase (BTK) inhibitors have greatly improved the spectrum of treatment options in mantle cell lymphoma (MCL) [1–4]. Acalabrutinib is a highly selective, orally administered, and potent BTK inhibitor with limited off-target activity [5]. Acalabrutinib was approved in 2017 by the US Food and Drug Administration for the treatment of relapsed/refractory MCL based on clinical data from the open-label, multicenter, phase 2 ACE-LY-004 study of acalabrutinib 100 mg twice daily [1]. Here, we present updated results from the ACE-LY-004 study after a median 26-month follow-up. Eligibility criteria and study design were published previously (Supplementary methods) [1]. Analysis of minimal residual disease (MRD) was conducted after complete response (CR) or partial response (PR) was achieved using the quantitative ClonoSEQ next-generation sequencing (5 × 10−6 ) assay (Adpative Biotechnologies, Seattle, WA, USA) in consenting patients with available paired archival tumor and whole blood samples. Data are updated as of February 12, 2018

Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years.

[en] BACKGROUND: Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin's lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. METHODS: This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). RESULTS: After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58-4.95), p < 0.001, and HR = 2.22 (95% CI 1.43-3.45), p < 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice

A French multicentric prospective prognostic cohort with epidemiological, clinical, biological and treatment information to improve knowledge on lymphoma patients: study protocol of the "REal world dAta in LYmphoma and survival in adults" (REALYSA) cohort.

BACKGROUND: Age-adjusted lymphoma incidence rates continue to rise in France since the early 80's, although rates have slowed since 2010 and vary across subtypes. Recent improvements in patient survival in major lymphoma subtypes at population level raise new questions about patient outcomes (i.e. quality of life, long-term sequelae). Epidemiological studies have investigated factors related to lymphoma risk, but few have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour mainly obtained from clinical trials data is partly biased because of patient selection. METHODS: The REALYSA ("REal world dAta in LYmphoma and Survival in Adults") study is a real-life multicentric cohort set up in French areas covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow-up. We aim to include 6000 patients over 4 to 5 years. Adult patients without lymphoma history and newly diagnosed with one of the following 7 lymphoma subtypes (diffuse large B-cell, follicular, marginal zone, mantle cell, Burkitt, Hodgkin, mature T-cell) are invited to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. Patients are treated according to the standard practice in their center. Clinical data, including treatment received, are extracted from patients' medical records. Patients' risk factors exposures and other epidemiological data are obtained at baseline by filling out a questionnaire during an interview led by a clinical research assistant. Biological samples are collected at baseline and during treatment. A virtual tumor biobank is constituted for baseline tumor samples. Follow-up data, both clinical and epidemiological, are collected every 6 months in the first 3 years and every year thereafter. DISCUSSION: This cohort constitutes an innovative platform for clinical, biological, epidemiological and socio-economic research projects and provides an opportunity to improve knowledge on factors associated to outcome of lymphoma patients in real life. TRIAL REGISTRATION: 2018-A01332-53, ClinicalTrials.gov identifier: NCT03869619

Depression in Patients with Mastocytosis: Prevalence, Features and Effects of Masitinib Therapy

Depression in patients with mastocytosis is often reported but its prevalence and characteristics are not precisely described. In addition, the impact of therapies targeting mast cells proliferation, differentiation and degranulation on psychic symptoms of depression have never been investigated. Our objective was to determine the prevalence and to describe features of depression in a large cohort of mastocytosis patients (n = 288) and to investigate the therapeutic impact of the protein kinase inhibitor masitinib in depression symptoms. The description of depression was based on the analysis of a database with Hamilton scores using Principal Component Analysis (PCA). Efficacy of masitinib therapy was evaluated using non parametric Wilcoxon test for paired data within a three months period (n = 35). Our results show that patients with indolent mastocytosis present an elevated prevalence of depression (64%). Depression was moderate in 56% but severe in 8% of cases. Core symptoms (such as psychic anxiety, depressed mood, work and interests) characterized depression in mastocytosis patients. Masitinib therapy was associated with significant improvement (67% of the cases) of overall depression, with 75% of recovery cases. Global Quality of Life slightly improved after masitinib therapy and did not predicted depression improvement. In conclusion, depression is very frequent in mastocytosis patients and masitinib therapy is associated with the reduction its psychic experiences. We conclude that depression in mastocytosis may originate from processes related to mast cells activation. Masitinib could therefore be a useful treatment for mastocytosis patients with depression and anxiety symptoms

Implications du médecin généraliste dans le suivi des patients atteints de leucémie lymphoïde chronique indolente en abstention thérapeutique

Introduction : L abstention thérapeutique dans le cadre d une Leucémie Lymphoïde Chronique (LLC) indolente peut induire chez le patient un sentiment d abandon . Notre étude a consisté à préciser les implications du médecin généraliste dans le suivi de ces patients en mesurant son rôle dans la compréhension de la pathologie, dans le suivi et la prise en charge des doléances du patient. Matériel et Méthodes : Nous avons réalisé une enquête de type non interventionnelle par envoi de questionnaires aux médecins généralistes de Picardie en charge de patients atteints de LLC en abstention thérapeutique. Résultats : 84 questionnaires ont été interprétés. Selon les médecins généralistes 28% des patients (n=24/84) avaient insuffisamment compris les explications de l hématologue, 67% (56/84) des patients ont abordé le sujet de la LLC en demandant de nouvelles explications. Ceux-ci ont décelé une inquiétude pour 23% (19/84) des patients avec un recours à un traitement anxiolytique pour 7 d entre-eux. La vaccination anti-grippale a été réalisée pour 80% des patients (67/84). Une asthénie a été retrouvée pour 31% des patients (26 patients/84). Les rythmes des examens cliniques et biologiques de surveillance réalisés par le médecin généraliste ont été dictés par la présence de co-morbidités. Discussion : Le médecin généraliste participe au suivi de patients atteints de LLC en abstention thérapeutique : aide à la compréhension et à l acceptation de la maladie, réalisation d un suivi clinique, biologique et des actes de médecine préventive (vaccination anti-grippale ). Conclusion : Ce suivi, pour être optimal, nécessiterait une standardisation par des règles de bonne pratique.Objectives: No treatment in the context of indolent chronic lymphocytic leukemia (CLL) may make some patients feel neglected. The aim of this study was to clarify the implications of general practitioners in the follow up of these patients. Study design: We conducted a survey by sending questionnaires to general practitioners in Picardy in charge of no treated CLL patients. Results: 84 questionnaires were interpreted. According to general practitioners, 28% (n=24/84) of patients understood insufficiently haematologist s explanations, 67% (56/84) needed further explanation about disease, 23% (19/84) were worried and 7 of them needed anxiolytic treatment. The influenza vaccination was performed to 80 patients (67/84). A weakness was found in 31% of patients (26/84).The frequency of clinical and biological follow up by the general practitioners was dependant of the presence of comorbidities. Conclusion: The general practitioner is involved in medical follow up of patients with CLL without treatment: helps to the understanding and acceptance of the disease, clinical and biological following, acts of preventive medicine. This follow up, to be optimal, require standardization by the rules of good practice.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Association de syndrômes lympho et myéloprolifératifs (description clinico-biologique et approche physiopathologique)

Les classifications actuelles des hémopathies selon le schéma classique myéloïde versus lymphoïde permettent l approche de la plupart des hémopathies. Cependant de rares patients présentent de manière concomitante ou non deux proliférations, l une myéloïde et l autre lymphoïde qu elles soient aigues ou chroniques. Cette association n est actuellement pas reconnue comme une entité, ne figure pas dans les classifications et est très peu décrite dans la littérature. Des données de la littérature associées à l expérience clinique, nous ont incité à étudier des cas de patients qui manifestent un tableau clinico-biologique pouvant correspondre à une association de proliférations lymphoïdes et myéloïdes. Nous rapportons dans ce travail une série de 8 patients ayant présenté un syndrome lymphoprolifératif et myéloprolifératif. Le but de ce travail est essentiellement de décrire leur présentation clinique et biologique. La discussion nous permettra de confronter notre série aux cas précédemment décrits et d aborder des hypothèses physiopathologiques plus larges notamment au vue des nouvelles avancées dans le domaine de l hématopoïèse et du concept de cellule souche leucémique.AMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Combining baseline TMTV and gene profiling for a better risk stratification in diffuse large B cell lymphoma

International audienceComment onCombination of baseline FDG PET/CT total metabolic tumour volume and gene expression profile have a robust predictive value in patients with diffuse large B-cell lymphoma. [Eur J Nucl Med Mol Imaging. 2018

[Evaluation of management disparity in patients with chronic lymphocytic leukemia in France]

Environmental factors have an impact on the effectiveness of treatments for chronic lymphocytic leukemia vulnerability, organization of the supply of care and proximity of the patient to health professionals. The disparity of care was assessed; vulnerability by the European index of deprivation, the provision of care by values of localized potential accessibility to general practitioners, nurses and pharmacists and hospital supply by the density of hematologists and time access to the center. The data, extracted from the public databases for each grouped island for statistical information, were cross-referenced to apply a principal component analysis and group them into 4 clusters. Cluster 1 has an average EDI, easy access to city professionals, remote access to the referral center, and a good density of hematologists. Cluster 2 has low EDI, satisfactory access to professionals, satisfactory proximity to the referral center and average density of hematologists. Cluster 3 has good EDI, access to professionals is difficult, access to the reference center is long, and the density of hematologists remains average. Cluster 4 has a good EDI, with access to professionals easier than in Cluster 3 but still difficult. The access time to the reference center is better than that of cluster 3 but remains elongated, the density of hematologists remaining average. Mapping is a tool for hospitals and institutions to evaluate care and compare it to other territories