The objective of this study was to compare the efficacy of two avian influenza (AI) H5-inactivated vaccines containing either an American (A/turkey/Wisconsin/68 H5N9; H5N9-WI) or a Eurasian isolate ...(A/chicken/Italy/22A/98 H5N9; H5N9-It). Three-week-old specific pathogen-free chickens were vaccinated once and challenged 3 wk later with a H5N1 highly pathogenic AI (HPAI) virus isolated from a chicken in Thailand in 2004. All unvaccinated challenged birds died within 2 days, whereas 90% and 100% of chickens vaccinated with H5N9-WI and H5N9-It, respectively, were protected against morbidity and mortality. Both vaccines prevented cloacal shedding and significantly reduced oral shedding of the challenge HPAI virus. Additional chickens (vaccinated or unvaccinated) were placed in contact with the directly challenged birds 18 hr after challenge. All unvaccinated chickens in contact with unvaccinated challenged birds died within 3 days after contact, whereas unvaccinated chickens in contact with vaccinated challenged birds either showed a significantly delayed mortality or did not become infected. All vaccinated contacts were protected against clinical signs, and most chickens did not shed detectable amount of HPAI virus. Altogether, these data indicate that both vaccines protected very well against morbidity and mortality and reduced or prevented shedding induced by direct or contact exposure to Asian H5N1 HPAI virus.
Introduction. Chimeric antigen receptor (CAR) T-cells have improved outcomes of patients (pts) with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). However, 40% to 60% of those pts ...will experience relapse or progression with a median overall survival (mOS) shorter than 6 months (mo) according to the French DESCAR-T registry study. Glofitamab is a 2:1 CD20xCD3 bispecific antibody that demonstrated efficacy in pts with R/R DLBCL. We report the results of the primary analysis of a phase II multicenter study using glofitamab in pts with R/R non-Hodgkin B-cell lymphoma after CAR T-cell infusion. Patients and Methods Pts with a biopsy-proven DLBCL (cohort 1) or non-DLBCL (cohort 2), with no metabolic response, progression or in relapse at least one month after CAR T-cell infusion, received obinutuzumab (1000 mg) 3 days before (Day -3, D-3) the first glofitamab dose. Intravenous glofitamab was administered with step-up dosing on D1 (2.5mg), D3 (10mg) and D8 (30mg) of Cycle (C) 1 and at 30mg on D1 of C2-11 (21-day cycles). The primary endpoint was defined for cohort 1 with a null hypothesis of 6.3 mo of mOS and a hypothesis of improvement to 12.6 mo (hazard ratio HR: 0.5). No hypothesis testing was planned for cohort 2. On Dec 22nd, 2022, enough events had been observed allowing the analysis of the primary endpoint based on data exported on June 2nd, 2023. Results. As of June 2 nd, 2023, 67 pts were enrolled, and 63 pts (44 pts in cohort 1, 19 pts in cohort 2) received ≥1 dose of study treatment. All pts in cohort 1 had a biopsy proven DLBCL whereas pts in cohort 2 had follicular lymphoma (n=6), mantle cell lymphoma (n=5), transformed follicular lymphoma (n=4), transformed marginal zone lymphoma (n=2), primary mediastinal B-lymphoma (n=1), or t-Waldenström macroglobulinemia(n=1). In combined cohort 1 and cohort 2, median age was 65 years (range: 33-77) and 84.1% of pts had Ann Arbor stage III/IV. Median number of prior therapies received was 3 (range: 2-6; ≥3 prior therapies: 87.3%; IPI ≥3: 58.7%). Prior CAR T-cell therapy was axi-cel (n=29, 46%), tisa-cel (n= 25, 39.7%), brexu-cel (n=5, 7.9%) or investigational CAR T-cell (n= 4, 6.3%). Thirteen pts (20.6%) were refractory (no response to CAR T-cells), 50 pts (79.4%) were in relapse/progression, among these, 15 (30%) relapsed/progressed between 1-3 mo, 18 (36%) between 3-6 mo and 17 (34%) >6mo after CAR T-cell infusion. The median number of glofitamab cycles administered was 5 (range: 1-12). Nine pts (14.3%) experienced cytokine release syndrome (CRS) (grade G1: 3 pts, G2: 6pts) and 2 pts experienced neurologic events (NE) G2. Neutropenia G ≥3 was observed in 22 pts (33.3%), thrombocytopenia G ≥3 in 9 pts (11.1%) and anemia G ≥3 in 7 pts (11.1%). Eighteen pts (28.6%) experienced serious adverse events (SAE) G ≥3, mainly infection (17 pts, among them 9 pts related to COVID-19). Thirty-five pts (55.5%) permanently discontinued glofitamab: 28 pts (44.4%) for progression, 4 pts for death and 3 pts for toxicity (musculoskeletal pain, hepatitis, genital infection). With a median follow-up of 9.7 mo (95% CI: 8.1-11.8), for cohort 1 the mOS was 17.6 mo (90% CI: 8.3-19.7), the lower limit of the 90% CI was ≥6.3 and so the null hypothesis could be rejected, and the primary endpoint was met. The mOS for cohort 2 was not reached (NR) (90% CI: 6.4-NR). According to central review, overall best metabolic response was 65.9% (CMR: 36.4%) and 57.9% (CMR 52.6%) in cohort 1 and 2, respectively. The median duration of CMR was 19.7 mo (95% CI: 4.9-19.7) and NR (95% CI: 2.8-NR) for cohort 1 and 2, respectively. Median progression-free survival was 4.9 mo (95% CI: 2.6-19.7) and 4.1 months (95% CI:1.4-NR for cohort 1 and 2, respectively). Conclusion. Glofitamab demonstrated a significant increase in OS when used in pts in first relapse/progression after CAR T-cells. In this context, glofitamab resulted in deep and durable responses and manageable safety.
Mixtures of turkey herpesvirus (HVT) and Rispens poultry vaccines have been used worldwide for over 20 yr, mainly for vaccination of future layers and breeders. With increasing virulence of Marek's ...disease (MD) virus strains, vaccination strategies are evolving toward the use of vaccines combining HVT and Rispens. A single vaccination either in ovo or at 1 day of age with the HVT + infectious bursal disease (IBD) vector vaccine is efficient against IBD. However, with vaccination programs that include a hatchery administration of the HVT + IBD vaccine, additional protection against very virulent and very virulent–plus MD viruses is needed, especially for layers and breeders. This study looked at the combination of four commercially available Rispens vaccines with the HVT + IBD vector vaccine injected at 1 day of age. MD challenge tests that were superior to 90% in relative score in all the groups vaccinated with both vaccines showed that the mixture of HVT + IBD and Rispens vaccines had no effect on clinical protection against MD, and IBD challenge tests showed that the mixture of HVT + IBD and Rispens vaccines had no effect on clinical protection against IBD, which was equal to 100% protection in all the groups vaccinated with both vaccines.
Juvenile temporal arteritis (JTA) is a recently-described and little-known inflammatory disease and its etiology is undetermined. Less than forty cases have been published. This paper is aimed at ...reporting the largest JTA series and to compare it to literature data to better evaluate its characteristics at diagnosis, its evolution and treatment options.
We conducted a retrospective and descriptive multicentric study in France by identifying adult patients under the age of 50 which had a pathological temporal artery biopsy owing to the presence of a temporal arteritis. Patients with temporal arteritis as a manifestation of systemic vasculitis were excluded.
We included 12 patients and the literature review identified 32 cases described in 27 articles, thus a total of 44 patients – 34 men and 10 women – with a median age of 30 and a maximum of 44. All patients presented either a lump in the temporal region or prominent temporal arteries, and 47.7% of patients suffered from headaches. Only 11.4% of patients presented general symptoms and 6.8% a biological inflammatory syndrome; 34.1% had peripheral blood eosinophilia; 83.7% presented a single episode and complete excision without further treatment was documented for 72.7%. Pathology analysis revealed infiltrate of inflammatory cells in the arterial wall in 97.6% of patients but also sparse giant cells for 25% and granuloma for 22.9%, perivascular extension of the inflammation for 82.6%, and presence of lymphoid follicles or germinal centres for 60%. Clinical relapses were present in 16.3% of cases.
JTA is a rare, localized and benign disease. The majority of cases have only one episode which is cured by local surgery.
•Juvenile temporal arteritis, is a rare, localized, and benign disease affecting the temporal artery in patients aged less than <50 years.•JTA presenting as a lump in the forehead, sometimes painful, without systemic symptoms or biological inflammation.•JTA is most frequently cured by biopsy or excision.•Kimura disease and angiolymphoid hyperplasia with eosinophilia must be considered as alternate diagnosis.
In this retrospective study, we report 70 cases of Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) among 1696 DLBCL-NOS cases diagnosed between 2006 and ...2019 (prevalence of 4.1%). At diagnosis, median age was 68.5 years; 79% of the cases presented with an advanced-stage disease (III-IV), 48% with extranodal lesions, and 14% with an hemophagocytic lymphohistiocytosis (HLH) (8 at diagnosis and 1 on therapy). A total of 46 cases presented a polymorphic pattern, and 21 were monomorphic. All had a non-germinal center B phenotype, with the majority of tumor cells expressing CD30 and programmed death ligand 1 (98% and 95%, respectively). Type II and III EBV latency was seen in 88% and 12% of the cases, respectively. Patients were treated with immunochemotherapy (59%) or chemotherapy (22%), and 19% received palliative care due to advanced age and altered performance status. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival (OS) at 5 years were 52.7% and 54.8%, respectively. Older age (>50 years) and HLH were associated with shorter PFS and OS in multivariate analysis (PFS: hazard ratio HR, 14.01; 95% confidence interval CI, 2.34-83.97; and HR, 5.78; 95% CI, 2.35-14.23; OS: HR, 12.41; 95% CI, 1.65-93.53; and HR, 6.09; 95% CI, 2.42-15.30, respectively). Finally, using a control cohort of 425 EBV− DLBCL-NOS, EBV positivity was associated with a shorter OS outcome within patients >50 years (5-year OS, 53% 95% CI, 38.2-74 vs 60.8% 95% CI, 55.4-69.3, P = .038), but not in younger patients.
•EBV+ DLCL-NOS is a heterogenous entity with regards to its pathological and clinical presentation, as well as its outcome.•Elderly EBV+ DLBCL-NOS patients have poorer OS than elderly EBV− DLBCL-NOS patients.
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Fowlpox (FP)-vectored avian influenza (FP-AI) vaccines are used in 1-day-old chickens, but they have also recently been shown to be immunogenic in ducks. The objectives of this work were 1) to ...evaluate safety and to compare the immunogenicity in ducks of three poxvirus vectors (fowlpox, canarypox, and vaccinia) expressing the same hemagglutinin gene from an H5N1 isolate, 2) to study the effect of the dose of the FP-AI and the presence of an adjuvant in 1-day-old Pekin ducks on antibody response after a boost with inactivated vaccine given 3 wk later, and 3) to confirm the immunogenicity of such a heterologous prime-boost vaccination scheme in 1-day-old Muscovy ducks. Immunogenicity induced by the three poxvirus vectors was comparable, and the FP vector was selected for the other studies. As published previously, there was a strong dose effect of the FP-AI priming on the hemagglutination inhibition (HI) titers induced after the boost with an inactivated vaccine. In contrast, the two tested adjuvants did not significantly increase the activity of FP-AI priming. The heterologous prime-boost regimen given to both Muscovy and Pekin ducklings at 1 and 14 or 21 days of age, respectively, was shown to be at least as immunogenic as two administrations of inactivated vaccines given at 2 and 5 wk of age. However, HI antibody titers were of short duration for both vaccine schemes, and their persistence was heterogeneous among individual birds.
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