Full Response of a Localized Renal Tumour after Reduced-Intensity Conditioned Hematopoietic Stem Cell Transplantation

Graft versus tumor effect has been described in solid metastatic tumor. We reported here the case of a patient treated for an acute myeloid leukemia with reduced-intensity conditioned allograft and the effect of this procedure on concomitant of renal localised cancer. The effect of immune-mediated cytotoxicity on renal cancer is the more consistent explanation to understand the necrosis of this tumor. Any case of RIC allograft has been reported before to treat localised renal tumor

Complement dependent cytotoxicity activity of therapeutic antibody fragments is acquired by immunogenic glycan coupling

Abstract Oligosaccharides are implicated in the development of the immune response notably in complement activation. Anti-tumoural immunotherapy by monoclonal antibodies (mAbs) offers some advantages to chemotherapy including cell targeting but some of them are inefficient to generate cytotoxicity dependent complement (CDC) known to be important in the antibody\u2019s efficacy. The aim of this study is to give a CDC activity of mAb by linkage of a complement activating oligosaccharide to this antibody via a hetero-bifunctional linker allowing control of the conjugation reaction. We worked on non Hodgkin Burkitt\u2019s lymphoma as cancer source, Fab fragments of rituximab devoid of complement activity as mAb and the trisaccharide Gal\u3b1(1\u21923)Gal\u3b2(1\u21924)GlcNAc as immunogenic glycan. The bioconjugate Fab-Gal was characterized by biochemical methods and we demonstrated that the \u3b1-Gal epitope was recognized by seric immunoglobulins. After checking the recognition capacity of the Fab- Gal conjugate for the CD20 epitope, in vitro assays were performed to evaluate the activation of the complement cascade by the Fab-Gal conjugate. The effect of this bioconjugate was confirmed by the evaluation of the proliferation response of Burkitt\u2019s cell line. The relative facility realization of this strategy represents new approaches to increase activities of mAbs

Agricultural pesticide exposure and the molecular connection to lymphomagenesis

The t(14;18) translocation constitutes the initiating event of a causative cascade leading to follicular lymphoma (FL). t(14;18) translocations are present in blood from healthy individuals, but there is a trend of increased prevalence in farmers exposed to pesticides, a group recently associated with higher risk of t(14;18)+ non-Hodgkin's lymphoma development. A direct connection between agricultural pesticide use, t(14;18) in blood, and malignant progression, however, has not yet been demonstrated. We followed t(14;18) clonal evolution over 9 yr in a cohort of farmers exposed to pesticides. We show that exposed individuals bear particularly high t(14;18) frequencies in blood because of a dramatic clonal expansion of activated t(14;18)+ B cells. We further demonstrate that such t(14;18)+ clones recapitulate the hallmark features of developmentally blocked FL cells, with some displaying aberrant activation-induced cytidine deaminase activity linked to malignant progression. Collectively, our data establish that expanded t(14;18)+ clones constitute bona fide precursors at various stages of FL development, and provide a molecular connection between agricultural pesticide exposure, t(14;18) frequency in blood, and clonal progression

Outcomes of Advanced Hodgkin Lymphoma after Umbilical Cord Blood Transplantation: A Eurocord and EBMT Lymphoma and Cellular Therapy & Immunobiology Working Party Study

Allogeneic stem cell transplantation is an alternative for patients with relapsed or refractory Hodgkin lymphoma (HL), but only limited data on unrelated umbilical cord blood transplantation (UCBT) are available. We analyzed 131 adults with HL who underwent UCBT in European Society for Blood and Marrow Transplantation centers from 2003 to 2015. Disease status at UCBT was complete remission (CR) in 59 patients (47%), and almost all patients had received a previous autologous stem cell transplantation. The 4-year progression-free survival (PFS) and overall survival (OS) were 26% (95% confidence interval [CI], 19% to 34%) and 46% (95% CI, 37% to 55%), respectively. Relapse incidence was 44% (95% CI, 36% to 54%), and nonrelapse mortality (NRM) was 31% (95% CI, 23% to 40%) at 4 years. In multivariate analysis refractory/relapsed disease status at UCBT was associated with increased relapse incidence (hazard ratio [HR], 3.14 [95% CI, 1.41 to 7.00], P = .005) and NRM (HR, 3.61 [95% CI, 1.58 to 8.27], P = .002) and lower PFS (HR, 3.45 [95% CI, 1.95 to 6.10], P < .001) and OS (HR, 3.10 [95% CI, 1.60 to 5.99], P = .001). Conditioning regimen with cyclophosphamide + fludarabine + 2 Gy total body irradiation (Cy+Flu+2GyTBI) was associated with decreased risk of NRM (HR, .26 [95% CI, .10 to .64], P = .004). Moreover, Cy+Flu+2GyTBI conditioning regimen was associated with a better OS (HR, .25 [95% CI, .12 to .50], P < .001) and PFS (HR, .51 [95% CI, .27 to .96], P = .04). UCBT is feasible in heavily pretreated patients with HL. The reduced-intensity conditioning regimen with Cy+Flu+2GyTBI is associated with a better OS and NRM. However, outcomes are poor in patients not in CR at UCBT

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

What prospective scenarios for 2035 will be compatible with reduced impact of French beef and dairy farm on climate change?

The agricultural sector is being called upon to reduce its greenhouse gas emissions (GHG). A scenario approachwas developed to explore the plausible futures of the French bovine sector and their impact on climate change.These scenarios encompass a Business As Usual scenario (S1-BAU) and alternative contrasting scenarios: (S2)cattle production increase to meet a high global demand under a liberal policy, (S3) refocus on internal demandwithin France, with an upmarket move to ‘green’ products, (S4) committed public policy to reduce GHGemissions. This paper analyses how key drivers of these scenarios (e.g. subsidies on investment, reduction ofmarket risks, carbon tax, limitation of concentrate feed in animal diets) affect the evolution of production,economics, and environmental impact on climate change of typical French suckler cow and dairy farms, bymeans of simulations performed with a bio-economic model. To adapt their farming systems to the scenarios,farms can opt for variably intensive/integrated practices per animal and per unit land area. Some technologicalprogress in animal production, crop production, and farm equipment is also modeled. Results show that in S1-BAU, milk production, net income and impact on climate change of dairy farms rise. Beef production and impacton climate change decrease slightly in suckler cow farms. Impact on climate change per unit of product decreasesowing to higher productivity per animal and to a more integrated management of crop production. Alternativescenarios underline that reorienting public support toward farm investment would further intensify dairy farmsand increase their income, but would reduce production and income of suckler cow farms and favor crop production(S2). Climate change impact per unit of product is more strongly reduced in S3 (organic farming withlow feed concentrate) than in S2, but with a reduced production, particularly for milk. A carbon tax decreasesemissions, but to the detriment of cattle production, especially suckler cow farms

Will French beef and dairy farms reduce their GHG emissions by 2035?

National audienc

Orfee: A bio-economic model to simulate integrated and intensive management of mixed crop-livestock farms and their greenhouse gas emissions

How do we plan future sustainable livestock farming systems? Some argue that intensive, specialized systems aremore efficient and emit fewer pollutants; others claim that integrated, diversified farming systems are morebeneficial to both society and the environment. Bio-economic farm models can help decision-makers and researchersanalyze the trade-offs among the numerous possibilities, and direct future livestock production towardgreater sustainability. The Orfee model described and evaluated here was developed with this aim. It covers abroad range of beef and dairy systems and forage and crop production alternatives that may be managed withvarying levels of intensity (breed, production objective, crop operations, etc.) and integration (crop rotation,organic fertilization, calving period, animal diets, etc.). Capital is also included in the optimization process, withtrade-offs between production, labor, machinery and buildings. Environmental impact is assessed through potentialimpact on climate change