A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging.

Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance.

An Integrated Cancer Prevention Strategy: the Viewpoint of the Leon Berard Comprehensive Cancer Center Lyon, France.

This article describes some of the key prevention services in the Leon Berard Comprehensive Cancer Center (CLB) Lyon, France, which are based on clinical prevention services, outreach activities, and collaboration with professional and territorial health communities. In addition, research is embedded at all stages of the prevention continuum, from understanding cancer causes through to the implementation of prevention interventions during and after cancer. Health promotion activities in the community and dedicated outpatient primary cancer prevention services for individuals at increased risk have been implemented.

Second line extracorporeal photopheresis for cortico-resistant acute and chronic GVHD after allogeneic hematopoietic cell transplantation for hematological malignancies: Long-term results from a real-life study.

Background & Objectives: The primary objective of this observational study was to perform an exhaustive description concerning patients receiving extracorporeal photopheresis (ECP) as second line treatment after steroid resistance for either acute or chronic GVHD following allo-HCT, secondary objectives were to evaluate the efficacy and long-term outcomes.

Study Design: A total of 106 patients were included, 65 (61%) males and 41 (39%) females with a median age at transplantation of 52 years (range: 20-67). ECP was initiated after transplantation either for acute GVHD [N = 25 (24%), 12 grade III and 13 grade IV] affecting skin alone (N = 5), gut alone (N = 12), gut and liver (N = 8), or chronic GVHD [N = 81 (76%), 15 (14%) limited and 66 (62%) extensive].

Pharmacokinetic Consideration of Venetoclax in Acute Myeloid Leukemia Patients: A Potential Candidate for TDM? A Short Communication.

Background: Venetoclax (VNX)-based regimens have demonstrated significantly favorable outcomes in patients with acute myeloid leukemia (AML) and are now becoming the standard treatment. Tyrosine kinase inhibitors are administered at a fixed dose, irrespective of body surface area or weight. For such orally targeted therapies, real-world data have highlighted a larger pharmacokinetic (PK) interindividual variability (IIV) than expected.

Spatial Transcriptomics Reveal Pitfalls and Opportunities for the Detection of Rare High-Plasticity Breast Cancer Subtypes.

Breast cancer is one of the most prominent types of cancers, in which therapeutic resistance is a major clinical concern. Specific subtypes, such as claudin-low and metaplastic breast carcinoma (MpBC), have been associated with high nongenetic plasticity, which can facilitate resistance. The similarities and differences between these orthogonal subtypes, identified by molecular and histopathological analyses, respectively, remain insufficiently characterized.

Activation of Nod2 signaling upon norovirus infection enhances antiviral immunity and susceptibility to colitis.

Over 90% of epidemic non-bacterial gastroenteritis are caused by human noroviruses (NoVs), which persist in a substantial subset of people allowing their spread worldwide. This has led to a significant number of endemic cases and up to 70,000 children deaths in developing countries. NoVs are primarily transmitted through the fecal-oral route.

Clinical outcome of therapy-related acute myeloid leukemia patients. Real-life experience in a University Hospital and a Cancer Center in France.

Background: t-AML occurs after a primary malignancy treatment and retains a poor prognosis.

Aims: To determine the impact of primary malignancies, therapeutic strategies, and prognostic factors on clinical outcomes of t-AML.

Results: A total of 112 adult patients were included in this study.

Outcomes of graft failure after umbilical cord blood transplantation in acute leukemia: a study from Eurocord and the Acute Leukemia Working Party of the EBMT.

Graft failure has remained a limitation of umbilical cord blood transplantation (CBT). Here, we assessed the outcomes of patients who experienced graft failure after CBT. Inclusion criteria were patients (age ≥ 18 years) experiencing graft failure after unrelated CBT (single or double) between 2005 and 2016, for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), no prior allogeneic or autologous transplantation, no other stem cell product.

Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile.

Retrospective, real-life study of venetoclax plus azacitidine or low-dose cytarabine in French patients with acute myeloid leukemia ineligible for intensive chemotherapy.

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.

Outcomes of subsequent neoplasms after umbilical cord blood transplantation in Europe.

Subsequent neoplasms (SNs) compromise long-term survivors after hematopoietic cell transplantation. We performed a retrospective analysis of SNs in 10 358 recipients of umbilical cord blood transplantation (UCBT) from 1988 to 2018. SNs developed in 233 patients and 84 were of pediatric age.

Meningeal macrophages protect against viral neuroinfection.

The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II MM were abundant neonatally, whereas MHC-II MM appeared over time.

Systemic antifungal strategies in allogeneic hematopoietic stem cell recipients hospitalized in french hematology units: a post-hoc analysis of the cross-sectional observational AFHEM study.

Background: Invasive fungal diseases (IFD) remain a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) and are associated with high mortality rates in patients receiving alloHSCT. Antifungal prophylaxis is increasingly being used in the management of IFDs in patients receiving alloHSCT.

Methods: A post-hoc analysis of the cross-sectional observational AFHEM study was carried out to describe the use of antifungal drugs in real-life clinical practice in alloHSCT recipients hospitalized in French hematological units.

Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the Chronic Malignancies Working Party of the EBMT.

While in vivo T-cell depletion (TCD) is widely used, its benefit in patients with MDS still remains a matter of debate. This study evaluates the impact of TCD on outcomes, and compares ATG and alemtuzumab, in patients with MDS. 1284 patients from the EBMT registry were included in this study with 470 patients in the no-TCD group and 814 in the TCD group (alemtuzumab N = 168; ATG N = 646).

Individualised physical activity programme in patients over 65 years with haematological malignancies (OCAPI): protocol for a single-arm feasibility trial.

Introduction: Older adults with cancer suffer from the combined effects of ageing, cancer disease and treatment side effects. The main treatment for patients with haematological malignancies is chemotherapy, associated with significant toxicities. Chemotherapy can alter patients' physical function and quality of life which are often already diminished in older patients due to ageing and comorbidities.

Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523).

Treating secondary antibody deficiency in patients with haematological malignancy: European expert consensus.

Objectives: Secondary antibody deficiency (SAD), associated with severe, recurrent or persistent infections, is common in patients with haematological malignancies (HM), but unifying guidance on immunoglobulin replacement therapy (IgRT) in these patients is lacking. We aimed to develop consensus statements for the use of IgRT in patients with HM.

Methods: A Delphi exercise was employed to test the level of agreement on statements developed by a Task Force based on available data and their clinical experience.