Haploidentical transplant with posttransplant cyclophosphamide vs matched related and unrelated donor transplant in acute myeloid leukemia and myelodysplastic neoplasm.

Hematopoietic cell transplantation from haploidentical donors (haploHCT) has facilitated treatment of AML and MDS by increasing donor availability and became more feasible since the introduction of post-transplant cyclophosphamide (ptCY). In our single-center retrospective analysis including 213 patients with AML or MDS, we compare the outcome of haploHCT (n = 40) with ptCY with HCT from HLA-identical MRD (n = 105) and MUD (n = 68). At 2 years after transplantation, overall survival (OS) after haploHCT was not significantly different (0.59; 95% confidence interval 0.44-0.79) compared to MRD (0.77; 0.67-0.88) and MUD transplantation (0.72; 0.64-0.82, p = 0.51). While progression-free survival (PFS) was also not significantly different (haploHCT: 0.60; 0.46-0.78, MRD: 0.55; 0.44-0.69, MUD: 0.64; 0.55-0.74, p = 0.64), non-relapse mortality (NRM) was significantly higher after haploHCT (0.18; 0.08-0.33) vs. MRD (0.029; 0.005-0.09) and MUD (0.06; 0.02-0.12, p < 0.05). Higher NRM was mainly caused by a higher rate of fatal infections, while deaths related to GvHD or other non-relapse reasons were rare in all groups. As most fatal infections occurred early and were bacterial related, one potential risk factor among many was identified in the significantly longer time to neutrophil engraftment after haploHCT with a median of 16 days (interquartile range; 14.8-20.0) vs. 12 days (10.0-13.0) for MRD and 11 days (10.0-13.0) for MUD (p = 0.01).

Complication rates of peripherally inserted central catheters vs implanted ports in patients receiving systemic anticancer therapy: A retrospective cohort study.

While implanted port catheters ("PORTs") have historically been the standard device for intravenous systemic anticancer therapy, the use of peripherally inserted central catheters (PICCs) has increased continuously and reliable catheter selection guidelines are lacking. We compare complication rates of PORTs and PICCs in cancer treatment in a retrospective study of 3365 patients with both solid organ (n = 2612) and hematologic (n = 753) malignancies, between 2001 and 2021. 26.4% (n = 890) of all patients were treated via PICCs and 73.6% (2475) via PORTs. 20.7% (578) experienced a major catheter-related complication with a higher rate in PICCs than in PORTs (23.5% vs 14.9%, P < .001). Among major complications, infections and mechanical complications were more common in PICCs than in PORTs (11.9% vs 6.4%, P = .001, 7.3% vs 4.2%, P = .002), whereas the rate of thrombosis was similar (3.4% vs 3.0%, P = .9). While PORTs had a higher rate of periprocedural complications (2.7% vs 1.1%, P < .05), PICCs overall complication rate exceeded PORTs within 3 days from implantation. Median follow-up was 49 (PICC) and 60 weeks (PORT). PORTs are safer and therefore should be preferred in this setting regardless of catheter dwell time.

Introducing innovative cellular therapies into the clinic: a 2-year retrospective experience of a chimeric antigen receptor T-cell programme at a single centre in Switzerland.

AIM OF THE STUDY: Chimeric antigen receptor T (CAR-T) cells are a powerful form of immune-cell therapy for patients with relapsed/refractory B-cell lymphoma and acute B lymphoblastic leukaemia. CAR-T cells have been commercially available in Switzerland since 2018. Because of the complexity and costs of this treatment it is critical to review patient outcomes in real-world settings, to examine whether the promising results from pivotal trials can be reproduced and to identify clinical parameters that determine their efficacy. METHODS: Here we present results of a retrospective study analysing outcomes of patients treated with CAR-T cells in a single academic centre in Switzerland during the first two years after commercial approval (BASEC-No. 2020-02271). Cytokine release syndrome (CRS), immune-cell associated neurotoxicity syndrome (ICANS), responses to treatment, ancillary laboratory studies and administrative specifics of CAR-T treatment were examined and are discussed. RESULTS: From October 2018 to August 2020 CAR-T cell therapy was evaluated in 34 patients, mostly with relapsed/refractory aggressive B-cell lymphoma (87% had refractory disease). Thirty-one patients underwent leukapheresis. Three of 31 patients (9.6%) died of rapid disease progression before the CAR-T cell product was delivered, two patients were enrolled into a clinical trial, three patients were not given CAR-T cells for other reasons. Ultimately, 23 patients were infused with a commercial CAR-T cell product and included in this analysis. Fourteen (61%) patients received bridging therapy while waiting for a median of 41 days (range 31-62) for delivery of the CAR-T cell product. Toxicity and severe side effects were rare (CRS >3 in 13%, ICANS > grade 3 in 10% of patients), manageable and resolved completely thereafter. The best overall response rate was 65%, with complete responses in 38% of lymphoma patients. At 12 months postinfusion, 61% of patients were alive and 35% progression free. With a median follow-up of 14 months, 13/23 (56%) patients were alive at the time of writing. CONCLUSION: CAR-T cell therapy proved to be safe and manageable under adequate hospital conditions. Outcomes resemble results from pivotal trials. The majority of patients was heavily pretreated and refractory at the time of CAR-T cell infusion. Patient selection, time point of leukapheresis, bridging strategies and timing of CAR-T cell infusion may be critical to further improve outcomes.

Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma.

Tumor cells orchestrate their microenvironment. Here, we provide biochemical, structural, functional, and clinical evidence that Cathepsin S (CTSS) alterations induce a tumor-promoting immune microenvironment in follicular lymphoma (FL). We found CTSS mutations at Y132 in 6% of FL (19/305). Another 13% (37/286) had CTSS amplification, which was associated with higher CTSS expression. CTSS Y132 mutations lead to accelerated autocatalytic conversion from an enzymatically inactive profrom to active CTSS and increased substrate cleavage, including CD74, which regulates major histocompatibility complex class II (MHC class II)-restricted antigen presentation. Lymphoma cells with hyperactive CTSS more efficiently activated antigen-specific CD4+ T cells in vitro. Tumors with hyperactive CTSS showed increased CD4+ T cell infiltration and proinflammatory cytokine perturbation in a mouse model and in human FLs. In mice, this CTSS-induced immune microenvironment promoted tumor growth. Clinically, patients with CTSS-hyperactive FL had better treatment outcomes with standard immunochemotherapies, indicating that these immunosuppressive regimens target both the lymphoma cells and the tumor-promoting immune microenvironment.

Correlation of Device Performance and Fermi Level Shift in the Emitting Layer of Organic Light-Emitting Diodes with Amine-Based Electron Injection Layers.

We investigate three amine-based polymers, polyethylenimine and two amino-functionalized polyfluorenes, as electron injection layers (EILs) in organic light-emitting diodes (OLEDs) and find correlations between the molecular structure of the polymers, the electronic alignment at the emitter/EIL interface, and the resulting device performance. X-ray photoelectron spectroscopy measurements of the emitter/EIL interface indicate that all three EIL polymers induce an upward shift of the Fermi level in the emitting layer close to the interface similar to n-type doping. The absolute value of this Fermi level shift, which can be explained by an electron transfer from the EIL polymers into the emitting layer, correlates with the number of nitrogen-containing groups in the side chains of the polymers. Whereas polyethylenimine (PEI) and one of the investigated polyfluorenes (PFCON-C) have six such groups per monomer unit, the second investigated polyfluorene (PFN) only possesses two. Consequently, we measure Fermi level shifts of 0.5-0.7 eV for PEI and PFCON-C and only 0.2 eV for PFN. As a result of these Fermi level shifts, the energetic barrier for electron injection is significantly lowered and OLEDs which comprise PEI or PFCON-C as an EIL exhibit a more than twofold higher luminous efficacy than OLEDs with PFN.

Degradation Mechanisms in Organic Light-Emitting Diodes with Polyethylenimine as a Solution-Processed Electron Injection Layer.

In this work, we investigate the performance and operational stability of solution-processed organic light-emitting diodes (OLEDs), which comprise polyethylenimine (PEI) as an electron injection layer (EIL). We show that the primary degradation mechanism in these OLEDs depends on the cathode metal that is used in contact with the EIL. In the case of Al, the deterioration in OLED performance during electrical driving is mainly caused by excitons which reach and subsequently degrade the emitter/PEI interface. In contrast, in the case of Ag, device performance degradation occurs due to an additional mechanism: hole accumulation at the emitter/PEI interface and a consequent drop in the emitter quantum yield. As a result, the operational lifetime of OLEDs that use PEI as EIL can vary significantly with the cathode material, and at a current density of 20 mA cm-2, LT50 lifetimes of ∼200 h and <10 h are obtained for Al and Ag, respectively. Finally, we show that the first degradation mechanism can be significantly slowed by using a mixture of PEI and ZnO nanoparticles as EIL. As a result, the operational lifetime of OLEDs with an Al cathode is increased to more than 1000 h, without adversely affecting device performance. This lifetime is significantly longer than that of a LiF/Al reference OLED.

High-Performance Electron Injection Layers with a Wide Processing Window from an Amidoamine-Functionalized Polyfluorene.

In this work, we present organic light-emitting diodes (OLEDs) utilizing a novel amidoamine-functionalized polyfluorene (PFCON-C) as an electron injection layer (EIL). PFCON-C consists of a polyfluorene backbone to which multiple tertiary amine side chains are connected via an amide group. The influence of molecular characteristics on electronic performance and morphological properties was tested and compared to that of the widely used, literature known amino-functionalized polyfluorene (PFN) and polyethylenimine (PEI). PFCON-C reduces the turn-on voltage (VON) of poly(p-phenylene vinylene) (PPV)-based OLEDs from ∼5 to ∼3 V and increases the maximum power efficiency from <2 to >5 lm W(-1) compared to that of PFN. As a result of its semiconducting backbone, PFCON-C is significantly less sensitive to the processing parameters than PEI, and comparable power efficiencies are achieved for devices where thicknesses of PFCON-C are between 15 and 35 nm. Atomic force microscopy (AFM) measurements indicate that the presence of nonpolar side chains in the EIL material is important for its film-forming behavior, while Kelvin probe measurements suggest that the amount of amine groups in the side chains influences the work-function shift induced by the EIL material. These results are used to suggest strategies for the design of polymeric electron injection layers.

Emissive Polyelectrolytes As Interlayer for Color Tuning and Electron Injection in Solution-Processed Light-Emitting Devices.

Herein we present a solution-processed hybrid device architecture combining organic light-emitting diodes (OLEDs) and light-emitting electrochemical cells (LECs) in a bilayer architecture. The LEC interlayer promotes the charge injection from an air-stable Ag cathode as well as permits the color tuning of the device emission. To this end, we used an alcohol-soluble anionic polyfluorene derivative, the properties of which were investigated by absorption and photoluminescence spectroscopy as well as by cyclic voltammetry. The bilayer device exhibited operating voltages ∼6 V and a color tuning of the emission spectrum dependent on the LEC interlayer thickness. The hybrid devices presented a color emission ranging from the yellow (x = 0.39, y = 0.47) toward the green region (x = 0.29, y = 0.4) of the Commission Internationale de I'Eclairage (CIE) 1931 chromaticity diagram.

Soluble diazaiptycenes: materials for solution-processed organic electronics.

The synthesis and characterization of soluble azaiptycenes is reported. Optical and physical properties were studied and compared with those of the structurally consanguine azaacenes. Electrochemical experiments and quantum-chemical calculations revealed the electronic structure of the iptycene derivatives. Their crystallization behavior was examined. A highly fluorescent amorphous diazatetracene derivative was integrated into a simple organic light-emitting diode, showing enhanced performance compared with that of previously reported, structurally similar tetracenes.

Investigation of solution-processed ultrathin electron injection layers for organic light-emitting diodes.

We study two types of water/alcohol-soluble aliphatic amines, polyethylenimine (PEI) and polyethylenimine-ethoxylated (PEIE), for their suitability as electron injection layers in solution-processed blue fluorescent organic light-emitting diodes (OLEDs). X-ray photoelectron spectroscopy is used to determine the nominal thickness of the polymer layers while ultraviolet photoelectron spectroscopy is carried out to determine the induced work-function change of the silver cathode. The determined work-function shifts are as high as 1.5 eV for PEI and 1.3 eV for PEIE. Furthermore, atomic force microscopy images reveal that homogeneous PEI and PEIE layers are present at nominal thicknesses of about 11 nm. Finally, we solution prepare blue emitting polymer-based OLEDs using PEI/PEIE in combination with Ag as cathode layers. Luminous efficiency reaches 3 and 2.2 cd A(-1), whereas maximum luminance values are as high as 8000 and 3000 cd m(-2) for PEI and PEIE injection layers, respectively. The prepared devices show a comparable performance to Ca/Ag OLEDs and an improved shelf lifetime.

The compromises of printing organic electronics: a case study of gravure-printed light-emitting electrochemical cells.

Light-emitting electrochemical cells (LECs) are fabricated by gravure printing. The compromise between device performance and printing quality is correlated to the ink formulation and the printing process. It is shown that the rheological properties of the ink formulations of LECs can be tailored without changing the chemical composition of the material blend.