L'introduction des chevaux en Amérique (leur évolution et leur rôle dans l'histoire des Etats-Unis)

LYON1-BU Santé (693882101) / SudocTOULOUSE-EN Vétérinaire (315552301) / SudocSudocFranceF

La Race bovine Abondance (situation actuelle et perspectives d'avenir)

LYON1-BU Santé (693882101) / SudocSudocFranceF

L'intoxication héréditaire au cuivre dans la race canine Bedlington Terrier (mise au point d'un test diagnostic moléculaire)

LYON1-BU Santé (693882101) / SudocTOULOUSE-EN Vétérinaire (315552301) / SudocSudocFranceF

Two Ways of Targeting a CD19 Positive Relapse of Acute Lymphoblastic Leukaemia after Anti-CD19 CAR-T Cells

Background: Therapeutic options for CD19+ relapses after anti-CD19 CAR-T cells are still debated; second infusion of anti-CD19 CAR-T cells, therapeutic antibodies, or targeted therapies can be discussed. Here, we explore the immunophenotyping and lysis sensitivity of CD19+ ALL relapse after anti-CD19 CAR-T cells and propose different therapeutic options for such a high-risk disease. Methods: Cells from successive B-ALL relapses from one patient were collected. A broad immunophenotype analysis was performed. 51Cr cytotoxic assays, and long-term killing assays were conducted using T-cell effectors that are capable of cytotoxicity through three recognition pathways: antibody-dependent cell-mediated cytotoxicity (ADCC), anti-CD19 CAR-T, and TCR. Results: Previously targeted antigen expression, even if maintained, decreased in relapses, and new targetable antigens appeared. Cytotoxic assays showed that ALL relapses remained sensitive to lysis mediated either by ADCC, CAR-T, or TCR, even if the lysis kinetics were different depending on the effector used. We also identified an immunosuppressive monocytic population in the last relapse sample that may have led to low persistence of CAR-T. Conclusion: CD19+ relapses of ALL remain sensitive to cell lysis mediated by T-cell effectors. In case of ALL relapses after immunotherapy, a large immunophenotype will make new therapies possible for controlling such high risk ALL

ALL relapse after anti-CD19 CAR-T cells therapy in a young adult: which therapeutic options?

International audienceT-cells expressing a Chimeric Antigen Receptor (CAR) recognizing the CD19 antigen allowed high early response rates in high-risk B acute lymphoblastic leukemias (B-ALL). Nevertheless, 35% to 44% of patients relapse. Among the mechanisms of immune evasion in CD19+ relapses of ALL, expression and secretion of molecules inhibiting cytotoxic T-lymphocytes, or lack of expression of co-stimulatory molecules, have been described. Expansion, persistence and cytotoxic activity of CAR-T cells could also be deficient.Here, we present the case of a young adult who presented successive relapses of ALL after chemotherapy, hematopoietic stem cell transplant (HSCT) and anti-CD19 CAR-T cells. An extended immunophenotype of leukemic cells and sensitivity to anti-CD19 CAR-T cells mediated lysis are analysed

Therapeutic targets in childhood B‐acute lymphoblastic leukemia: what about HER2/neu?

International audienceNo abstract availabl

Extensive myelitis with eosinophilic meningitis after Chimeric antigen receptor T cells therapy

Abstract Immune effector cell‐associated neurotoxicity syndrome (ICANS) is a frequent adverse event after Chimeric antigen receptor T cells (CAR‐T cells). A patient treated with anti‐CD19 CAR‐T cells for a refractory mantle cell lymphoma presented at Day 8 post‐infusion with extensive myelitis. Unusual eosinophilia was disclosed in the patient's cerebrospinal fluid. After treatment with methylprednisolone and siltuximab, a decrease in clinical symptoms and magnetic resonance imaging lesions were obtained. This unprecedented presentation of eosinophilic meningitis after CAR‐T cells therapy highlights the need for a better understanding of the physiopathology of ICANS, especially to identify potentially targetable pathways

Added value of molecular karyotype in childhood acute lymphoblastic leukemia

Abstract Background Thanks to an improved therapeutic regimen in childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), 5 year‐overall survival now exceeds 90%. Unfortunately, the 25% of children who relapse have an initial poor prognosis, potentially driven by pre‐existing or emerging molecular anomalies. The latter are initially and essentially identified by cytogenetics. However, some subtle alterations are not visible through karyotyping. Methods Single nucleotide polymorphisms (SNP) array is an alternative way of chromosomal analysis allowing for a more in‐depth evaluation of chromosomal modifications such as the assessment of copy number alterations (CNA) and loss of heterozygosity (LOH). This method was applied here in retrospective diagnosis/relapse paired samples from seven children with BCP‐ALL and in a prospective cohort of 38 newly diagnosed childhood cases. Results In the matched study, compared to the initial karyotype, SNP array analysis reclassified two patients as poor prognosis cases. Modulation during relapse was seen for 4 CNA and 0.9 LOH. In the prospective study, SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor prognosis. Ultimately, in all the children tested, SNP array allowed to identify additional anomalies compared to conventional karyotype, refine its prognostic value and identify some druggable anomalies that could be used for precision medicine. Overall, the anomalies detected could be segregated in four groups respectively involved in B‐cell development, cell proliferation, transcription and molecular pathways. Conclusion SNP therefore appears to be a method of choice in the integrated diagnosis of BCP ALL, especially for patients initially classified as intermediate prognosis. This complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques

Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients

International audienceA full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients

SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine

International audienceBackground: At variance to humoral responses, cellular immunity after anti-SARS-CoV-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT), especially within the first post-transplant years where immunosuppression is more profound and harmful. Methods: SARS-CoV-2 Spike protein-specific T-cell responses were explored after two doses of BNT162b2 mRNA vaccine in 45 Allo-HSCT recipients with a median time from transplant of less than 2 years by using INF-γ ELISPOT assay and flow-cytometry enumeration of CD4+ and CD8+ T lymphocytes with intracellular cytokine production of IFN-γ and TNF-α. Results: A strong TNF-α+ response from SARS-CoV-2-specific CD4+ T-cells was detected in a majority of humoral responders (89%) as well as in a consistent population of non-humoral responders (40%). Conclusions: T-cells are likely to participate in protection against COVID-19 viral infection, even in the absence of detectable antibody response, especially in the first years post-transplant in Allo- HSCT recipients