Kirkshannon3756

Plasma cell leukemia (PCL) is a rare and very aggressive plasma cell disorder. The optimal treatment approach, including whether to pursue an autologous (auto) or allogeneic (allo) stem cell transplantation (SCT) is not clear, given the lack of clinical trial-based evidence. This single-center retrospective study describes the outcomes of 16 patients with PCL (n = 14 with primary PCL) who underwent either autoSCT (n = 9) or alloSCT (n = 7) for PCL in the era of novel agents, between 2007 and 2019. The median age of the cohort was 58 years. High-risk cytogenetics were found in 50% of the patients. All patients received a proteasome inhibitor and/or immunomodulatory drug-based regimen before transplantation. At the time of transplantation, 10 patients (62%) obtained at least a very good partial response (VGPR). The response after autoSCT (3 months) was at least a VGPR in 6 patients (67%; complete response [CR] in 5). All patients undergoing alloSCT achieved a CR at 3 months. Maintenance therapy was provided to 5 patients (56%) after autoSCT. The median progression-free survival after transplantation was 6 months in the autoSCT group, compared with 18 months in the alloSCT group (P = .09), and median overall survival (OS) after transplantation in the 2 groups was 19 months and 40 months, respectively (P = .41). The median OS from diagnosis was 27 months and 49 months, respectively (P = .50). Of the 11 deaths, 10 patients (91%) died of relapsed disease. AlloSCT was not observed to offer any significant survival advantage over autoSCT in PCL, in agreement with recent reports, and relapse remains the primary cause of death in these patients.

Graft versus host disease (GVHD) remains a significant cause of non-relapse mortality (NRM) after haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). The cumulative incidence rate of acute GVHD grade 2-4 at day 100 is higher than that in matched sibling donor PBSCT. Patients with glucocorticoid-refractory acute GVHD responded poorly to rescue therapies and had inferior survival due to uncontrolled GVHD and infections. Ruxolitinib, a selective Janus kinase (JAK) 1/2 inhibitor, has been approved for the treatment of steroid-refractory acute GVHD. Ruxolitinib showed tolerance and safety during second-line therapy in terms of virus reactivation and malignant recurrence. In addition, pilot studies showed that Ruxolitinib exerted anti-leukemic effects on hematological malignancies such as myelodysplastic syndromes, acute myeloid leukemia and acute lymphoblastic leukemia.

This study aims to prospectively evaluate the efficacy and safety of Ruxolitinib combined with 1 mg/kg methylprednisolone alleviated toxicity and resulted in long-term survival.

Patients with intermediate or high risk acute GVHD obtained a high response rate to Ruxolitinib (5 mg daily) combined with 1 mg/kg/day methylprednisolone. The novel regimen spared steroid exposure, alleviated toxicity and resulted in long-term survival.In the setting of T cell-depleted, full-haplotype mismatched transplantation, adoptive immunotherapy with regulatory T cells (Tregs) and conventional T cells (Tcons) can prevent graft-versus-host disease (GVHD) and improve post-transplantation immunologic reconstitution and is associated with a powerful graft-versus-leukemia effect. To improve the purity and the quantity of the infused Tregs, good manufacturing practices (GMP)-compatible expansion protocols are needed. Here we expanded Tregs using an automated, clinical-grade protocol. Cells were extensively characterized in vitro, and their efficiency was tested in vivo in a mouse model. Tregs were selected by CliniMacs (CD4+CD25+, 94.5 ± 6.3%; FoxP3+, 63.7 ± 11.5%; CD127+, 20 ± 3%; suppressive activity, 60 ± 7%), and an aliquot of 100 × 106 was expanded for 14 days using the CliniMACS Prodigy System, obtaining 684 ± 279 × 106 cells (CD4+CD25+, 99.6 ± 0.2%; FoxP3+, 82 ± 8%; CD127+, 1.1 ± 0.8%; suppressive activity, 75 ± 12%). CD39 and CTLA4 expression levels increased from 22.4 ± 12% to 58.1 ± 13.3% (P 95%). When sorted populations were analyzed, TIM3+ cells showed significant increases in IL-10 and granzyme B (P less then .01) .When expanded Tregs were infused in an NSG murine model, mice that received Tcons only died of GVHD, whereas mice that received both Tcons and Tregs survived without GVHD. GMP grade expanded cells that display phenotypic and functional Treg characteristics can be obtained using a fully automated system. Treg suppression is mediated by multiple overlapping mechanisms (eg, CTLA-4, CD39, IL-10, IL-35, TGF-β, granzyme B). TIM3+ cells emerge as a potentially highly suppressive population. © 2020 American Society for Transplantation and Cellular Therapy. learn more Published by Elsevier Inc.Addiction can be conceptualised as a disorder of maladaptive learning and memory. Therefore, maladaptive drug memories supporting drug-seeking and relapse behaviours may present novel treatment targets for therapeutic approaches based upon reconsolidation-blockade. It is known that different structures within the limbic corticostriatal system contribute differentially to different types of maladaptive drug memories, including pavlovian associations between environmental cues and contexts with the drug high, and instrumental memories underlying drug-seeking. Here, we review the mechanisms underlying drug memory reconsolidation in the amygdala, striatum, and hippocampus, noting similarities and differences, and opportunities for future research.

To investigate the association between levels of diabetes mellitus (DM) control and rates of visual field and retinal nerve fiber layer (RNFL) loss over time in glaucoma.

Retrospective cohort study.

A total of 351 eyes of 222 patients with type 2 DM with concomitant primary open-angle glaucoma (POAG) or suspected glaucoma extracted from the Duke Glaucoma Registry.

All patients had at least 2 reliable standard automated perimetry (SAP) tests, 2 spectral domain OCT (SD-OCT) tests, and 2 glycated hemoglobin (HbA1c) measures over time with a minimum follow-up of 6 months. Values of HbA1c were summarized for each patient as mean, peak, and fluctuation across time. Multivariable linear mixed models were used to estimate the effect of HbA1c on rates of change in SAP mean deviation (MD) and OCT RNFL thickness loss over time while adjusting for various confounding factors.

Rates of change in MD and RNFL thickness over time.

Subjects had a mean baseline age of 62.5 ± 10.2 years and follow-up time of 6.9 ± 5.