Late relapse after hematopoietic stem cell transplantation for acute leukemia: a retrospective study by SFGM-TC.

peer reviewedLate relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity

Caractérisation des mécanismes de résistance au vénétoclax dans la leucémie lymphoïde chronique : résultats préliminaires de l'étude RAVEN

CONTEXTE. Le développement des thérapies ciblées telles que l’inhibiteur de BCL2 vénétoclax a considérablement enrichi la prise en charge thérapeutique de la leucémie lymphoïde chronique (LLC). Malgré cette efficacité, des cas de patients résistants émergents et plusieurs mécanismes peuvent être impliqués : mutations du gène BCL2 perturbant la liaison du vénétoclax à sa cible ; hyperexpression du gène et de la protéine MCL1 résultant dans certains cas d’une amplification de la région chromosomique 1q21 et hyperexpression de la protéine BCL-XL, toutes deux compensant l’inhibition de BCL2 ; modifications du métabolisme énergétique. À ce jour, ces mécanismes sont décrits de façon isolée dans de petites cohortes.OBJECTIFS. L’objectif principal de l’étude RAVEN est d’identifier la fréquence des marqueurs de résistance au vénétoclax au sein d’une cohorte de LLC en rechute et ou réfractaire (R/R).MÉTHODE. Cette étude nationale est promue par le CHU de Clermont-Ferrand. Il s’agit d’une étude observationnelle, française, multicentrique où tout patient majeur atteint d’une LLC en R/R à un traitement par vénétoclax peut être inclus. Les échantillons tumoraux (sang, moelle osseuse et/ou ganglion lymphatique) sont collectés au temps avant et après traitement par vénétoclax. Les données clinico-biologiques des patients aux temps « diagnostic », « avant traitement » et « après traitement » par vénétoclax sont recueillies. Les analyses biologiques protocolaires réalisées comportent le séquençage de nouvelle génération (NGS) du gène BCL2 ainsi que la recherche d’amplification de la région chromosomique 1q21 en Fluorescence In Situ par Hybridation (FISH).RÉSULTATS. Entre le 07/03/22 et le 31/08/22, treize patients ont été inclus (huit hommes et cinq femmes) avec un âge médian de 58 ans. La médiane de lignes de traitement reçus était de trois. Le vénétoclax était le plus souvent administré en deuxième (30,8 % des cas) ou troisième (30,8 % des cas) ligne. Sept (53,8 %) patients avaient reçu un inhibiteur de la Bruton Tyrosine Kinase (ibrutinib) au préalable. Deux patients (15,4 %) avaient reçu un schéma de vénétoclax à durée fixe. Quatre patients (30,8 %) ont rechuté sous forme de transformation en lymphome de haut grade et neuf (69,2 %) sous forme de LLC. Au diagnostic, deux patients (15,4 %) présentaient une trisomie 12, trois (23,1 %) une délétion 17p, trois (23,1 %) une délétion 11q et trois (23,1 %) un caryotype complexe. Notre analyse de comparaison avant/après vénétoclax a montré une évolution clonale cytogénétique pour cinq patients et une évolution clonale moléculaire pour cinq patients. Les résultats de séquençage NGS ont révélé la disparition des marques de résistances à l’ibrutinib pour trois des quatre patients concernés. Aucune mutation de BCL2 n’a été mise en évidence sur huit patients analysés et une amplification de la région chromosomique 1q21 a été identifiée sur huit patients analysés.CONCLUSION. Notre étude RAVEN retrouve une faible prévalence des marqueurs connus comme liés à la résistance au vénétoclax dans la LLC (mutations du gène cible BCL2 en séquençage NGS et amplification de la région chromosomique 1q21 en FISH). Des analyses complémentaires sont en cours pour affiner la détection des mutations de BCL2 (PCR digitale) et quantifier l’hyperexpression de MCL1 par approche moléculaire (RT PCR quantitative) et cellulaire (quantification par cytométrie en flux)

Les CAR-T cells sont là !

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Tranexamic acid in non-traumatic intracranial bleeding: a systematic review and meta-analysis

International audienceNon-traumatic intracranial bleeding (NTIB), comprising subarachnoid hemorrhage (SAH) and intra-cranial bleeding (ICH) is a significant public health concern. Tranexamic acid (TXA) is a promising treatment with benefits yet to be fully demonstrated. We conducted a systematic review and meta-analysis on the impact of TXA on mortality in NTIB. We searched the PubMed, Cochrane Library, Google Scholar and ScienceDirect databases for studies reporting mortality data following the use of TXA in NTIB for comparisons with a control group. We computed random-effect meta-analysis on estimates of risk and sensitivity analyses. We computed meta-regression to examine the putative effects of the severity of NTIB, sociodemographic data (age, sex), and publication date. Among potentially 10,008 articles, we included 15 studies representing a total of 4883 patients: 2455 receiving TXA and 2428 controls; 1110 died (23%) during the follow-up. The meta-analysis demonstrated a potential of 22% decrease in mortality for patients treated by TXA (RR=0.78, 95%CI 0.58-0.98, p=0.002). Meta-regression did not demonstrate any influence of the severity of NTIB, age, sex, length of treatment or date of publication. Sensitivity analyses confirmed benefits of TXA on mortality. TXA appears to be a therapeutic option to reduce non-traumatic intracranial bleeding mortality, particularly in patients with SAH

The Negative Impact of Night Shifts on Diet in Emergency Healthcare Workers

International audienceDespite the consequences of night-shift work, the diet of night-shift workers has not been widely studied. To date, there are no studies related to food intake among emergency healthcare workers (HCWs). We performed a prospective observational study to assess the influence of night work on the diet of emergency HCWs. We monitored 24-h food intake during a day shift and the consecutive night, and during night work and the daytime beforehand. We analyzed 184 emergency HCWs’ food intakes. Emergency HCWs had 14.7% lower (−206 kcal) of their 24-h energy intake during night shifts compared to their day-shift colleagues (1606.7 ± 748.2 vs. 1400.4 ± 708.3 kcal, p = 0.049) and a 16.7% decrease in water consumption (1451.4 ± 496.8 vs. 1208.3 ± 513.9 mL/day, p = 0.010). Compared to day shifts, night-shift had 8.7% lower carbohydrates, 17.6% proteins, and 18.7% lipids. During the night shift the proportion of emergency HCWs who did not drink for 4 h, 8 h and 12 h increased by 20.5%, 17.5%, and 9.1%, respectively. For those who did not eat for 4 h, 8 h and 12 h increased by 46.8%, 27.7%, and 17.7%, respectively. A night shift has a huge negative impact on both the amount and quality of nutrients consumed by emergency healthcare workers

Impact of Air Transport on SpO2/FiO2 among Critical COVID-19 Patients during the First Pandemic Wave in France

International audienceDuring the first wave of the COVID-19 pandemic, some French regions were more affected than others. To relieve those areas most affected, the French government organized transfers of critical patients, notably by plane or helicopter. Our objective was to investigate the impact of such transfers on the pulse oximetric saturation (SpO2)-to-inspired fraction of oxygen (FiO2) ratio among transferred critical patients with COVID-19. We conducted a retrospective study on medical and paramedical records. The primary endpoint was the change in SpO2/FiO2 during transfers. Thirty-eight patients were transferred between 28 March and 5 April 2020, with a mean age of 62.4 years and a mean body mass index of 29.8 kg/m2. The population was 69.7% male, and the leading medical history was hypertension (42.1%), diabetes (34.2%), and dyslipidemia (18.4%). Of 28 patients with full data, we found a decrease of 28.9 points in SpO2/FiO2 (95% confidence interval, 5.8 to 52.1, p = 0.01) between the starting and the arrival intensive care units (SpO2/FiO2, 187.3 ± 61.3 and 158.4 ± 62.8 mmHg, respectively). Air medical transfers organized to relieve intensive care unit teams under surging conditions during the first COVID wave were associated with significant decreases in arterial oxygenation

First‐line treatment of double‐hit and triple‐hit lymphomas: Survival and tolerance data from a retrospective multicenter French study

International audienceHistorically, double or triple hit lymphoma (DHL and THL) have poor outcomes with conventional chemotherapy, but there is currently no guideline. We report the French experience in managing DHL and THL in first line using collective data on both survival and tolerance. All consecutive patients with newly diagnosis of large B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements, as determined by FISH between January 2013 and April 2019 were included. Based on the eligibility criteria, 160 patients were selected among the 184 patients identified. With a median follow-up of 32 months, 2- and 4-year progression free survival (PFS) rates were 40% and 28% with R-CHOP compared with 57% and 52% with intensive chemotherapy (P = .063). There was no difference in overall survival (OS). For advanced stages, PFS was significantly longer with intensive chemotherapy than with R-CHOP (P = .029). There was no impact of autologous stem cell transplantation among patient in remission. For patients with central nervous system (CNS) involvement, the 2-year PFS and OS rate was 21% and 39%, vs 57% and 75% without CNS disease (P = .007 and P < .001). By multivariate analysis, elevated IPI score and CNS disease were strongly and independently associated with a poorer survival, whereas treatment was not significantly associated with OS. This is the largest series reporting the treatment of DHL and THL in Europe. The PFS was significantly longer with an intensive regimen for advanced stage, but no difference in OS, supporting the need for a prospective randomized trial