Highly Sensitive and Accurate Assessment of Minimal Residual Disease in Chronic Lymphocytic Leukemia Using the Novel CD160-ROR1 Assay.

Undetectable minimal residual disease (MRD) in Chronic Lymphocytic Leukemia (CLL) has a favorable prognostic outcome compared with MRD that can be detected. This study investigated a flow cytometric assay (CD160-ROR1FCA) targeting the tumor-specific antigens CD160 and receptor tyrosine kinase-like orphan receptor 1 (ROR1), along with CD2, CD5, CD19, CD45. CD160-ROR1FCA was compared with the originally published 8-colour European Research Initiative for CLL (ERIC) gold-standard assay for CLL MRD detection.

National mycology laboratory diagnostic capacity for invasive fungal diseases in 2017: Evidence of sub-optimal practice.

A survey of laboratory testing capabilities for systemic fungal pathogens was undertaken in the UK, to identify where improved compliance with published standards and guidelines is required and to inform antifungal stewardship (AFS). The survey captured information from laboratories in the UK on diagnostic capacity for invasive fungal diseases (IFD), including identification, serology, molecular diagnostics and susceptibility testing. The survey was circulated in March 2017 through key networks.

Increased autocrine interleukin-6 production is significantly associated with worse clinical outcome in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) remains incurable with current standard therapy. We have previously reported that an increased expression of interleukin-6 (IL-6) receptor CD126 leads to resistance of CLL cells to chemotherapy and worse prognosis for patients with CLL. In this study, we determine whether autocrine IL-6 production by CLL B cells is associated with poor clinical outcome and explore IL-6-mediated survival mechanism in primary CLL cells.

An investigation of antifungal stewardship programmes in England.

Purpose: We sought to explore the current status of antifungal stewardship (AFS) initiatives across National Health Service (NHS) Trusts within England, the challenges and barriers, as well as ways to improve current AFS programmes.

Methodology: An electronic survey was sent to all 155 acute NHS Trusts in England. A total of 47 Trusts, corresponding to 30 % of English acute Trusts, responded to the the survey; 46 Trusts (98 %) had an antimicrobial stewardship (AMS) programme but only 5 (11 %) had a dedicated AFS programme.

Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia.

Objectives: To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL).

Patients And Methods: In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD.

A CONSORT analysis of randomised controlled trials for the treatment of invasive aspergillosis.

There is no assessment of the reporting quality of antifungal randomized, controlled trials (RCT), upon which guidelines for the treatment of invasive aspergillosis (IA) in patients with hematological malignancy are based. Trial reports were identified through Trip, Cochrane, Medline, and Embase database searches. Report quality was assessed using the 25-item CONSORT checklist and a rating scale of 1 (strongly disagree) to 4 (strongly agree).

STAT3 and NF-κB cooperatively control in vitro spontaneous apoptosis and poor chemo-responsiveness in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is an adult disease characterized by in vivo accumulation of mature CD5/CD19/CD23 triple positive B cells and is currently incurable. CLL cells undergo spontaneous apoptosis in response to in vitro cell culture condition but the underlying mechanism is unclear. We hypothesize that the sensitivity of CLL cells to spontaneous apoptosis may be associated with the constitutive activities of transcription factors STAT3 and/or NF-κB.

CD126 and Targeted Therapy with Tocilizumab in Chronic Lymphocytic Leukemia.

Purpose: IL6 promotes tumor growth and signal transduction via both its membrane-bound (CD126) and soluble receptors (sCD126). We aimed to study whether the levels of CD126 expression in chronic lymphocytic leukemic (CLL) cells can predict in vitro and in vivo treatment response.

Experimental Design: The levels of membrane-bound CD126 expression were determined on freshly isolated CLL B cells (n = 58) using flow cytometry.

Dynamin-related protein Drp1 is required for Bax translocation to mitochondria in response to irradiation-induced apoptosis.

Translocation of the pro-apoptotic protein Bax from the cytosol to the mitochondria is a crucial step in DNA damage-mediated apoptosis, and is also found to be involved in mitochondrial fragmentation. Irradiation-induced cytochrome c release and apoptosis was associated with Bax activation, but not mitochondrial fragmentation. Both Bax and Drp1 translocated from the cytosol to the mitochondria in response to irradiation.

Aspergillus-Specific Lateral-Flow Device and Real-Time PCR Testing of Bronchoalveolar Lavage Fluid: a Combination Biomarker Approach for Clinical Diagnosis of Invasive Pulmonary Aspergillosis.

Clinical experience with the impact of serum biomarkers for invasive fungal disease (IFD) varies markedly in hemato-oncology. Invasive pulmonary aspergillosis (IPA) is the most common manifestation, so we evaluated biomarkers in bronchoalveolar lavage (BAL) fluid. An Aspergillus-specific lateral-flow device (LFD), quantitative real-time PCR (qPCR), and the galactomannan (GM) test were used with 32 BAL fluid samples from 32 patients at risk of IPA.

Use of biosimilar filgrastim compared with lenograstim in autologous haematopoietic stem-cell transplant and in sibling allogeneic transplant.

Objectives: Biosimilar filgrastim was compared with lenograstim for autologous haematopoietic stem-cell transplant (HSCT) in patients with haematological malignancies. Data from a separate group of sibling donors who underwent allogeneic HSCT are also reported.

Methods: Patients with lymphoma or multiple myeloma (MM) who underwent autologous HSCT with biosimilar filgrastim were compared with a historical control group of patients who received lenograstim.

Significant decline in Galactomannan Signal during storage of clinical serum samples.

Galactomannan (GM) is widely used for detection of invasive aspergillosis in high-risk haemato-oncology patients. Recent publications have reported a lack of repeatability of GM detection. The objective of this retrospective study was to assess the repeatability of GM levels during storage of clinical samples.

A MIQE-compliant real-time PCR assay for Aspergillus detection.

The polymerase chain reaction (PCR) is widely used as a diagnostic tool in clinical laboratories and is particularly effective for detecting and identifying infectious agents for which routine culture and microscopy methods are inadequate. Invasive fungal disease (IFD) is a major cause of morbidity and mortality in immunosuppressed patients, and optimal diagnostic criteria are contentious. Although PCR-based methods have long been used for the diagnosis of invasive aspergillosis (IA), variable performance in clinical practice has limited their value.

Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis.

Diagnosis of invasive aspergillosis (IA) remains a challenge as the clinical manifestations are not specific, and a histological diagnosis is often unfeasible. The 2002 European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria for classification of cases into possible, probable or proven were revised in 2008. Our objective was to analyze the impact of these revisions on the diagnosis of IA.

Differential and tumor-specific expression of CD160 in B-cell malignancies.

CD160 is a human natural killer (NK)-cell-activating receptor that is also expressed on T-cell subsets. In the present study, we examined 811 consecutive cases of B-cell lymphoproliferative disorders (B-LPDs), and demonstrated CD160 expression in 98% (590 of 600) of chronic lymphocytic leukemia (CLL) cases, 100% (32 of 32) of hairy cell leukemia (HCL) cases, 15% (5 of 34) of mantle cell lymphoma (MCL) in the leukemic phase, and 16% (23 of 145) of other B-LPD cases. CD160 transcript and protein were absent in the normal B-cell hierarchy, from stem cells, B-cell precursors, maturing B cells in the germinal center, and circulating B cells, including CD5(+)CD19(+) B1 cells in umbilical cord.

CD160 signaling mediates PI3K-dependent survival and growth signals in chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (CLL) expresses CD160, a glycosylphosphatidylinositol-linked receptor found on normal natural killer (NK) and T cells, but not B cells. CD160 is a multifunctional molecule in normal lymphocytes, but its role in CLL biology is unknown. In vitro, CLL cells undergo rapid spontaneous apoptosis, which CD160 activation protected against-mean cell viability increased from 67% to 79% (P < .

Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(-) fraction.

Leukemia-initiating cells (LICs) in acute myeloid leukemia (AML) are believed to be restricted to the CD34(+) fraction. However, one of the most frequently mutated genes in AML is nucleophosmin (NPM), and this is associated with low CD34 expression. We, therefore, investigated whether NPM-mutated AMLs have LICs restricted to the CD34(+) fraction.

Dietary flavonoids inhibit the anticancer effects of the proteasome inhibitor bortezomib.

Dietary flavonoids have many health-promoting actions, including anticancer activity via proteasome inhibition. Bor-tezomib is a dipeptide boronate proteasome inhibitor that has activity in the treatment of multiple myeloma but is not effective in chronic lymphocytic leukemia (CLL). Although CLL cells are sensitive in vitro to bortezomib-induced apoptosis when cultured in medium, the killing activity was blocked when cultured in 50% fresh autologous plasma.