The modified prophylactic DLI strategy might represent a step forward in the treatment of advanced leukemia.

To date, the research on dendritic cells (DCs) and their correlated neoplasms has not been clear. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and mature plasmacytoid dendritic cell proliferation (MPDCP) are two types of malignancies originating from plasmacytoid dendritic cells (pDCs). Some evidence has indicated the existence of other pDC neoplasms. In addition, cases of myeloid neoplasms (MNs), acute myeloblastic leukemia (AML), and myelodysplastic syndrome (MDS) with increased pDCs (AML/MDS-pDCs) seem to have immature DCs according to the vaguely consistent expression of markers among MNs and pDCs, which appear to fit the developmental pattern of normal DCs. We analyzed 14 AML/MDS-pDC cases mainly for their immunophenotype by flow cytometry and inferred their CD expression pattern. The patients' clinical information and other laboratory data were collected and reviewed. AML/MDS-pDCs show a different pattern of markers from BPDCN and MPDCP. Three maturation-involved stages were found in these AML/MDS-pDCs patients. Stage I was the most immature stage and displayed an expression profile of CD34 +/st+ CD117 +/st+ BDCA2 − BDCA4 − CD123 + HLA-DR +/st+ CD4 − CD45dim + ; Stage II was the more immature stage displayed a phenotype of CD34 dim+ CD117 dim+ BDCA2 −/dim+ BDCA4 −/dim+ CD123 st+ HLA-DR +/st+ CD4 − CD45 + ; and Stage III was the mature stage showed CD34 − CD117 − BDCA2 + /BDCA4 + CD123 st+ HLA-DR +/st+ CD4 + CD45 +/st+ . Three maturation-involved stages overlapped well with the phenotypes of normal DC progenitors in a continuously developmental process: granulocyte, monocyte, and DC progenitors (GMDPs) and/or monocyte and DC progenitors (MDPs), common DC progenitors (CDPs), pDCs, and/or pre-DCs. In this study, we considered AML/MDS-pDCs as entities that were distinct from BPDCN and MPDCP and correlated the components of this tumor with the normal DC differentiation pathway, which provides new evidence for understanding DC neoplasms.

BackgroundCurdione is one of the most highly concentrated component of the active constituents in E-zhu, which has been reported to possess a variety of activities. However, the pharmacologic neuroprotective activity of curdione has not been evaluated. The present study aimed to investigate the protective effect of curdione on focal cerebral ischemia reperfusion-induced injury in rats and further exploring the underlying mechanisms.Materials and methodsAdult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO) surgery for 2 h, followed by reperfusion stage. All animals received treatment once a day for 7 days before surgery and 14 days from 4 h after the reperfusion started. The neurological deficit test and Morris water maze test were performed at 1, 4, 7 and 14 days after MCAO. The infarct size of animals was determined by the 2,3,5-triphenyltetrazolium chloride staining, and pathological brain damage was estimated by hematoxylin–eosin staining. The malonaldehyde (MDA) levels and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) were detected by enzyme-linked immunosorbent assay. Expression of apoptotic proteins was measured by Western blot.ResultsOur results showed that curdione could significantly reduce the infarct size and neurological deficits, promote cognitive function recovery and recover neuronal morphologic damages in MCAO rats. It also blocked the increase of MDA content and elevated the activities of SOD, CAT and GSH-PX. Moreover, curdione attenuated the expression of Cyt-C, c-caspase-3 and c-caspase-9 increased the Bcl-2/Bax ratio and hence decreased the cellular apoptosis.ConclusionCurdione possessed potential neuroprotective effect on rats in the MCAO model. The anti-oxidative and anti-apoptotic properties may be involved in the underlying mechanisms.

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Glomeruli instance segmentation from pathologic images is a fundamental step in the automatic analysis of renal biopsies. Glomerular histologic manifestations vary widely among diseases and cases, and several special staining methods are necessary for pathologic diagnosis. A robust model is needed to segment and classify glomeruli with different staining methods and apply in cases with various glomerular pathologic changes. Herein, pathologic images from renal biopsy slides stained with three basic special staining methods were used to build the data sets. The snapshot group included 1970 glomeruli from 516 patients, and the whole-slide image group included 8665 glomeruli from 148 patients. Cascade Mask region-based convolutional neural net architecture was trained to detect, classify, and segment glomeruli into three categories: i) GN, structural normal; ii) global sclerosis; and iii) glomerular with other lesions. In the snapshot group, total glomeruli, GN, global sclerosis, and glomerular with other lesions achieved an F1 score of 0.914, 0.896, 0.681, and 0.756, respectively, which were comparable with those in the whole-slide image group (0.940, 0.839, 0.806, and 0.753, respectively). Among the three categories, GN achieved the best instance segmentation effect in both groups, as determined by average precision, average recall, F1 score, and Mask mean Intersection over Union. The present model segments and classifies multistained glomeruli with efficiency and robustness. It can be applied as the first step for more detailed glomerular histologic analysis.

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Introduction Immune thrombocytopenia (ITP) is an acquired, organ-specific, autoimmune disease and one of the most common bleeding disorders seriously endangering human health. Glucocorticoids and intravenous immunoglobulin are first-line treatments recommended by guidelines for patients with ITP. However, approximately 50%-85% of patients relapse during the first year of treatment. In addition, long-term use of glucocorticoids increases the risk for dose- and time-dependent glucocorticoid-related complications and serious side effects. Therefore, in-depth studies investigating new solutions for the first-line treatment of ITP are urgently needed. Tacrolimus is a calcineurin inhibitor, which forms a complex by binding to FK506-binding protein. It is currently widely used in the prevention of graft-versus-host disease for organ transplantation as well as for the treatment of autoimmune diseases. In addition to recent retrospective studies and case reports demonstrating its effectiveness in ITP, tacrolimus has been shown to improve anti-platelet antibody-mediated thrombocytopenia in mice, suggesting it may be a potential treatment for ITP. The aim of this study was to compare two first-line treatment options for ITP-a standard glucocorticoid-only regimen versus tacrolimus in combination with a standard glucocorticoid regimen-to determine which could help patients achieve stable platelet counts faster and experience a longer duration of remission. Methods This open-label, randomized, phase 2 trial, enrolled adult ITP patients from seven different tertiary medical centers in China. Elderly patients had confirmed, newly diagnosed, treatment-naive ITP, platelet counts <30×10 9/L, or < 50×10 9/L and significant bleeding symptoms (World Health Organization bleeding scale ≥ 2). Eligible patients were randomly assigned 1:1 with an interactive web-based response system to receive either oral tacrolimus (initial 0.03 mg/kg/day and maintain blood concentration at 3-5 ng/mL for 12 weeks) plus high-dose dexamethasone (HD-DXM) or HD-DXM monotherapy for 12 weeks. DXM (40 mg) was administered orally daily for 4 consecutive days to both study arms. The 4-day course of DXM was repeated on days 11-14 in patients who lacked response by day 10. The primary endpoint was 6-month sustained response (SR), defined as platelet count maintained >50×10 9/L without any additional ITP-modifying therapy at the 6-month follow-up. Key secondary endpoints included initial response by day 14 (OR, platelet count ≥30×10 9/L and at least 2-fold increase in baseline platelet count and absence of bleeding; and CR, platelet count ≥ 100×10 9/L), duration of response, bleeding scores, and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04747080). Results Total 140 patients newly diagnosed with ITP were randomly assigned to either the tacrolimus plus HD-DXM (n=72) or HD-DXM monotherapy (n=68) groups. At the 6-month follow-up, the proportion of patients exhibiting SR was significantly higher in the tacrolimus plus HD-DXM group than in the HD-DXM monotherapy group (65.3% vs 42.6%, p= 0.007). Of the 140 patients with ITP (males accounted for 48.6%), the mean age was 32.8 years, the mean platelet count was 16.7×10 9/L. The combination group exhibited a higher 14-day early remission rate than the monotherapy group (76.4% vs 55.9%, P=0.001). Significantly fewer treatment failures occurred in patients randomly assigned to the combination group(19.4% vs 38.2%, P=0.0014). During the follow-up period, fewer patients in the combination group experienced relapse than in the monotherapy group; the median time to relapse was 77 days (Tacrolimus+HD-DXM) vs 36 days (HD-DXM). The combination group exhibited a lower proportion of bleeding events and a lower bleeding score. The incidence of serious AEs, rescue therapy, and treatment side effects were similar between the two groups, and treatment was well tolerated by all patients, with no grade 4 AEs or treatment-related deaths reported. There was no statistically significant difference in the incidence of treatment-related AEs between the two groups. Conclusions Low-dose tacrolimus plus HD-DXM was an effective and safe treatment for ITP as first-line therapy and elicited a sustained prolonged response in adults. This therapy may be a new treatment option for adult patients with ITP. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: It includes information or discussion of off-label drug use of tacrilimus.

Objectives To compare the efficacy and safety of Chinese generic imatinib with branded imatinib in adults with newly diagnosed chronic myeloid leukemia in the chronic phase (CML-CP). Methods Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei®, Hansoh, China; Genike®, Chiatai Tianqing, China) or branded imatinib (Glivec®, Novartis, Basel, Switzerland) between October 2013 and August 2018, during which both of the agents were commercially available in China, were retrospectively reviewed. Propensity score matching (PSM) case-control study was performed. Assessment of cytogenetic and molecular responses, failure-free survival (FFS), progression-free survival (PFS), and overall survival (OS) was according to European LeukemiaNet recommendation. Assessment of adverse events was according to Common Terminology Criteria for Adverse Events version 4.03. Cox regression model was used to identify independent factors associated with the responses and outcomes. Results In total, 442 adults receiving Chinese generic imatinib (n=236) or Glivec® (n=206) at an initial dose of 400mg once daily were included. 273 (61.6%) patients were male. Median age was 41 years (range, 18-83 years). Higher white blood cell (WBC) counts (P=0.019), rural household registration (P<0.001), lower education level (P<0.001), and divorced or widowed status (P=0.009) were more common in the Chinese generic imatinib cohort than those in the branded imatinib cohort. There was no significant difference in gender, age, Sokal risk, hemoglobin (HGB) level and basophile percentage in peripheral blood at diagnosis between the 2 cohorts. With the median follow-up of 30 months (range, 3-62 months) and 34 months (range, 3-67 months) in the generic and branded cohorts, respectively, there was no significant difference on the 4-year probabilities of achieving complete cytogenetic response (CCyR, 97% vs. 97.2%, P=0.851), major molecular response (MMR, 87.8% vs. 90.1%, P=0.131), molecular response 4.0 (MR4.0, 55.0% vs. 68.3%, P=0.169), molecular response 4.5 (MR4.5, 32.8% vs. 39.2%, P=0.191) as well as the 4-year probabilities of FFS (77.4% vs.81.1%, P=0.363), PFS (94.4% vs. 95.9%, P=0.480) and OS (95.8% vs. 98.3%, P=0.086) between the Chinese generic imatinib and Glivec cohorts. Multivariate analyses showed the type of drug was not associated with the cytogenetic and molecular responses and outcomes. However, male gender, education level, Sokal risk, WBC counts, HGB level and basophile percentage in peripheral blood at diagnosis were significantly associated with the responses or outcomes (Table 1). There was no significant difference on hematologic (P=0.923) and non-hematologic (P=0.655) adverse events between the 2 cohorts. After the PSM adjustment for gender, age, household registration, education level, marriage status, Sokal risk, WBC count and HGB level, 150 pairs of case-control patients with comparable baseline characteristics were re-analyzed. Similarly, multivariate analyses confirmed that Chinese generic or branded imatinib used as the front-line therapy was not associated with either responses or outcomes. Conclusions Socio-demographics might influenced patients' choice of the type of TKI used. Chinese generic imatinib and Glivec® as frontline therapy had comparable efficacy and safety in CML-CP patients. Disclosures No relevant conflicts of interest to declare.