Topic: 22. Stem cell transplantation - Clinical Background: Despite novel biologic agents, steroid-dependent or -refractory acute graft-versus-host disease (aGVHD) remains a severe complication of allogeneic hematopoietic cell transplantation (alloHCT). Aims: Based on our long-lasting experience with extracorporeal photopheresis (ECP), we aimed to prospectively assess the role of ECP as early second-line treatment in steroid-dependent and refractory aGVHD. Methods: We enrolled consecutive patients with steroid-dependent or refractory grade (gr) II-IV aGVHD post alloHCT over the last decade (January 2013 - December 2022). All patients with unrelated or haploidentical donors received thymoglobulin (ATG) 5mg/kg as prophylaxis. Post-transplant GVHD prophylaxis included cyclosporine – methotrexate in myeloablative and cyclosporine – mycophenolate mofetil in reduced toxicity or intensity regimens. ECP was commenced after assessment of response to 5 days of steroid treatment according to our protocol: 2 sessions/week for 1 month, 1 session/2 weeks for 3 months, evaluation of response and 1 session/month for 6 months. Before ruxolitinib’s availability, ATG was commenced simultaneously with ECP initiation in steroid-refractory patients. Results: We studied 28 patients, aged 45 (18-67), post alloHCT with myeloablative (16), reduced toxicity (8) and intensity (4) conditioning, from sibling (4), matched (11) or one locus mismatched (12) volunteer unrelated and haploidentical (1) donors. Disease risk index was very high (1), high (11), intermediate (14) and low (2). Acute GVHD was observed at day +17 (8-50). Skin, intestine and liver involvement was evident in 9 patients, skin and intestine in 13 and skin only in 6 patients. Thirteen patients were steroid-dependent and 15 steroid-refractory. ECP was commenced at day +18 (8-56) for 15 (4-20) sessions. The majority of patients (19/27) presented partial (7), very good (11) or complete (1) response to ECP. With 9.9 (1.7-113) months of follow-up, immunosuppression was reduced in 12/27 and ceased in 1 patient. Clinically significant bacterial infections were found in 19 patients, fungal in 3, CMV and EBV reactivation in 19 and 12 respectively and other viral in 6 patients. Cumulative incidence (CI) of chronic GVHD was 56.4 at 1-year.Five-year overall survival (OS) was 34%. Reduction of immunosuppression (p=0.026) and number of ECP sessions (p<0.001) were associated with improved OS, irrespectively of other factors. In particular, optimal OS was observed in patients that received more than 19 ECP sessions (Figure). Summary/Conclusion: Our data confirm that ECP should be considered early in the course of steroid-dependent or refractory aGVHD, even in the era of novel biologic agents. Optimal timing of intervention, frequency, duration and tapering schedule of ECP remain important unanswered questions.Keywords: Allogeneic, Graft-versus-host disease (GVHD), Hematopoietic cell transplantation, Extracorporeal photopheresis
This work, for the first time, assessed the secondary aerosol formation from both in-use diesel and natural gas heavy-duty vehicles of different vocations when they were operated on a chassis dynamometer while the vehicles were exercised on different driving cycles. Testing was performed on natural gas vehicles equipped with three-way catalysts (TWCs) and diesel trucks equipped with diesel oxidation catalysts, diesel particulate filters, and selective catalytic reduction systems. Secondary aerosol was measured after introducing dilute exhaust into a 30 m3 environmental chamber. Particulate matter ranged from 0.18 to 0.53 mg/mile for the diesel vehicles vs 1.4–85 mg/mile for the natural gas vehicles, total particle number ranged from 4.01 × 1012 to 3.61 × 1013 for the diesel vehicles vs 5.68 × 1012–2.75 × 1015 for the natural gas vehicles, and nonmethane organic gas emissions ranged from 0.032 to 0.05 mg/mile for the diesel vehicles vs 0.012–1.35 mg/mile for the natural gas vehicles. Ammonia formation was favored in the TWC and was found in higher concentrations for the natural gas vehicles (ranged from ∼0 to 1.75 g/mile) than diesel vehicles (ranged from ∼0 to 0.4 g/mile), leading to substantial secondary ammonium nitrate formation (ranging from 8.5 to 98.8 mg/mile for the natural gas vehicles). For the diesel vehicles, one had a secondary ammonium nitrate of 18.5 mg/mile, while the other showed essentially no secondary ammonium nitrate formation. The advanced aftertreatment controls in diesel vehicles resulted in almost negligible secondary organic aerosol (SOA) formation (ranging from 0.046 to 2.04 mg/mile), while the natural gas vehicles led to elevated SOA formation that was likely sourced from the engine lubricating oil (ranging from 3.11 to 39.7 mg/mile). For two natural gas vehicles, the contribution of lightly oxidized lubricating oil in the primary organic aerosol was dominant (as shown in the mass spectra analysis), leading to enhanced SOA mass. Heavily oxidized lubricating oil was also observed to contribute to the SOA formation for other natural gas vehicles.
Endothelial injury indices, such as Endothelial Activation and Stress Index (EASIX), modified EASIX (m-EASIX), and simplified EASIX (s-EASIX) scores, have been previously associated with chimeric antigen receptor-T (CAR-T) cell immunotherapy complications. Soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor-15 (GDF-15), and soluble C5b-9 (sC5b-9) have been described as markers of endothelial injury post-hematopoietic stem cell transplantation. In the current study, we examined whether suPAR, GDF-15, and sC5b-9 levels were associated with endothelial injury indices in adult CAR-T cell recipients. The levels of these markers were measured in patients before CAR-T cell infusion and in healthy individuals with immunoenzymatic methods. We studied 45 CAR-T cell recipients and 20 healthy individuals as the control group. SuPAR, GDF-15, and sC5b-9 levels were significantly higher in the patients' group compared to the healthy control group (
This study investigates the impact of low concentration biodiesel blends on the regulated, carbonyl and PAH emissions from a modern passenger vehicle. The vehicle was a Euro 4 compliant SUV type fitted with a common-rail diesel engine and a diesel oxidation catalyst. Emission and fuel consumption measurements were performed on a chassis dynamometer using a constant volume sampling (CVS) technique, following the European regulations. All measurements were conducted over the NEDC and Artemis driving cycles. Aiming to evaluate the fuel impact on emissions, a soy-based biodiesel was blended with an ultra low sulphur diesel at proportions of 10 and 30% by volume. The experimental results revealed that emissions of PM, HC and CO decreased with biodiesel over most driving conditions. Some increases were observed over the NEDC which may be attributed to the cold-start effect and to certain fuel characteristics. NOx emissions were found to be higher with biodiesel especially during Artemis operation. CO2 emissions and fuel consumption followed similar patterns and increased with biodiesel. Most carbonyl compound emissions increased with biodiesel, with the exception of aromatic aldehydes. It was found that carbonyl emissions decreased as the mean speed and load of the driving cycle was increased. Most PAH emissions were found to be lower with biodiesel, however, some increases were observed for certain toxic compounds.
