Endogenous and exogenous cytokines: An overview and introduction.

Cytokines are ubiquitous small proteins, secreted by virtually all leukocytes and other immune effector cells, that interact with other cytokines and effector and regulatory cells to direct innate and adaptive immunity. Six broad categories of cytokines have been described, with functions ranging from stimulation of immunity and inflammation by cytokines produced by white blood cells (interleukins) to impacting the migration of immune effector cells to sites of inflammation and tissue injury (chemokines). When secreted in excess, or when there exists an imbalance between proinflammatory and anti-inflammatory cytokines, diseases ranging from sepsis to organ transplant rejection to autoimmune disorders occur.

Signalling Network Analysis of Blood Mononuclear Cells From Clinical Samples by Bivariate Correlation.

Signalling networks have been assessed in blood cells by assessing individual phosphoantigens. We considered the possibility that bivariate correlations involving a series of signalling molecules could be used to delineate functional signalling networks in cells from clinical samples. Here, we describe a novel approach to signalling network analysis using enhanced flow cytometry to provide increased resolving power and restricted-dimensional cytometry which simplifies the analysis so that the precision of the analysis is optimised.

Efficacy of Total-Body Irradiation-based Intensified Myeloablative Regimens for Acute Leukemia-An International Collaborative Study.

Background: In this study, we compared outcomes of intensified myeloablative conditioning regimens using large registry data from Japan (Japanese Society for Transplantation and Cellular Therapy) and the United States (Center for International Blood and Marrow Transplant Research).

Methods: Adult patients who underwent their first myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia in remission between 2010 and 2018 using conditioning regimens of cyclophosphamide plus total-body irradiation (CY/TBI), CY/TBI+cytarabine (AraC), or CY/TBI+etoposide (VP16) were included.

Results: The acute myeloid leukemia (AML) cohort ( = 480, 38.

Human mesenchymal stem cell therapy: Potential advances for reducing cystic fibrosis infection and organ inflammation.

Innovation in cystic fibrosis (CF) supportive care, including implementing new antimicrobial agents, improved physiotherapy, and highly effective modulators therapy, has advanced patient survival into the 4th and 5th decades of life. However, even with these remarkable improvements in therapy, CF patients continue to suffer from pulmonary infection and other visceral organ complications associated with long-term deficient cystic fibrosis transmembrane conductance regulator (CFTR) expression. Human mesenchymal stem cells (MSCs) have been utilized in tissue engineering based upon their capacity to provide structural components of mesenchymal tissues.

Delayed T-cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults.

Allogeneic hematopoietic cell transplantation (allo-HCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T- and B-cell recovery have improved survival and decreased treatment-related mortality (TRM). A total of 2089 patients were included who underwent first allo-HCT for acute myeloid leukemia/acute lymphoblastic leukemia/myelodysplastic syndrome from 2008 to 2019 reported to the Center for International Blood and Marrow Transplant Research with available CD4 counts at days 100 and 180.

Recombinant Myeloid Hematopoietic Growth Factors and Clinical Stimulation of Acute Myeloid Leukemia Cells: A Narrative Review.

Background: The advent of molecularly cloned hematopoietic growth factors (rhuG-CSF and rhuGM-CSF) enhanced the safety in treating acute myeloid leukemia (AML) by reducing the duration of neutropenia and thus decreasing the risks for infection. However, early in vitro studies demonstrated leukemia cell proliferation in response to these agents, raising reasonable concerns related to whether these factors can cause or contribute to relapse or progression of AML.

Summary: Clinical studies using recombinant myeloid hematopoietic growth factors have supported their safety, as there is little or no clear evidence for an association with an increased risk of relapse in AML in patients, regardless of the hematopoietic growth factor used, or whether the setting of AML is newly diagnosed or relapsed/refractory.

Cytokine therapy of acute radiation syndrome.

Radiological accidents/incidents are common with nearly 400 reported since 1944 exposing about 3000 people to substantial doses of ionizing radiations with 127 deaths. Damage to hematopoietic stem and progenitor cells with resulting bone marrow failure is a common consequence of exposure to whole body acute high-dose and -dose-rate ionizing radiations and is termed hematopoietic-acute radiation syndrome, or H-ARS. Therapy of H-ARS includes transfusions, anti-bacterial and -viral drugs, molecularly-cloned hematopoietic growth factors and hematopoietic cell transplants.

Analyte heterogeneity analysis as a possible potency parameter for MSC.

Mesenchymal stem/stromal cells (MSC) have been transplanted for therapeutic purposes with inconsistent results. MSC preparations are heterogeneous, and this person-to-person heterogeneity may account for the variable clinical outcomes. Additionally, the mechanisms of therapeutic action for MSC are unclear which confounds attempts to understand and identify factors that may account for variable clinical results.

Neuro-toxicities of chemo- and immune-therapies in haematologic malignancies: from mechanism to management.

Chemo- and immune therapies administered to treat haematologic malignancies frequently cause neurologic injury. The adverse events range from mild cognitive impairment and headaches to severe conditions such as seizures, stroke and encephalitis. We performed a comprehensive literature review and report the types, mechanisms, management and prevention of neuro-toxicity resulting from these therapies in subjects who develop these toxic effects.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

Cancer cytogenetics in a genomics world: Wedding the old with the new.

Since the discovery of the Philadelphia chromosome in 1960, cytogenetic studies have been instrumental in detecting chromosomal abnormalities that can inform cancer diagnosis, treatment, and risk assessment efforts. The initial expansion of cancer cytogenetics was with fluorescence in situ hybridization (FISH) to assess submicroscopic alterations in dividing or non-dividing cells and has grown into the incorporation of chromosomal microarrays (CMA), and next generation sequencing (NGS). These molecular technologies add additional dimensions to the genomic assessment of cancers by uncovering cytogenetically invisible molecular markers.

Possible Role of Correlation Coefficients and Network Analysis of Multiple Intracellular Proteins in Blood Cells of Patients with Bipolar Disorder in Studying the Mechanism of Lithium Responsiveness: A Proof-Concept Study.

The mechanism of lithium treatment responsiveness in bipolar disorder (BD) remains unclear. The aim of this study was to explore the utility of correlation coefficients and protein-to-protein interaction (PPI) network analyses of intracellular proteins in monocytes and CD4 lymphocytes of patients with BD in studying the potential mechanism of lithium treatment responsiveness. Patients with bipolar I or II disorder who were diagnosed with the MINI for DSM-5 and at any phase of the illness with at least mild symptom severity and received lithium (serum level ≥ 0.

Cell-type specific molecular expression levels by restricted-dimensional cytometry.

Background: Cytometric analysis has been commonly used to delineate distinct cell subpopulations among peripheral blood mononuclear cells by the differential expression of surface receptors. This capability has reached its apogee with high-dimensional approaches such as mass cytometry and spectral cytometry that include simultaneous assessment of 20-50 analytes. Unfortunately, this approach also engenders significant complexity with analytical and interpretational pitfalls.

Targeting hematologic malignancies by inhibiting E-selectin: A sweet spot for AML therapy?

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewis) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo.

Sargramostim for Prophylactic Management of Gastrointestinal Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy for Cancer.

Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3-4 treatment-related adverse events, including gastrointestinal (GI) toxicities which are common. These GI immune-related adverse events (irAEs) induced by ICIs present significant clinical challenges, require prompt intervention, and result in treatment delays or discontinuations.

Impact of Visceral Obesity on Clinical Outcome and Quality of Life for Patients with Multiple Myeloma: A Secondary Data Analysis of STaMINA (BMT CTN 0702) Trial.

Obesity is a common health problem in patients with multiple myeloma (MM) that has been linked to poor clinical outcomes and quality of life (QoL). We conducted a secondary analysis of the BMT CTN 0702, a randomized, controlled trial comparing outcomes of 3 treatment interventions after a single hematopoietic cell transplantation (HCT) (n = 758), to investigate the impact of visceral obesity, as measured by waist-to-hip ratio (WHR), on clinical outcomes and QoL in MM patients. A total of 549 MM patients, median age 55.

GM-CSF, G-CSF or no cytokine therapy with anti-GD2 immunotherapy for high-risk neuroblastoma.

Colony-stimulating factors have been shown to improve anti-disialoganglioside 2 (anti-GD2) monoclonal antibody response in high-risk neuroblastoma by enhancing antibody-dependent cell-mediated cytotoxicity (ADCC). A substantial amount of research has focused on recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant to anti-GD2 monoclonal antibodies. There may be a disparity in care among patients as access to GM-CSF therapy and anti-GD2 monoclonal antibodies is not uniform.

The role of randomized controlled trials, registries, observational databases in evaluating new interventions.

Approaches to comparing safety and efficacy of interventions include analyzing data from randomized controlled trials (RCTs), registries and observational databases (ODBs). RCTs are regarded as the gold standard but data from such trials are sometimes unavailable because a disease is uncommon, because the intervention is uncommon, because of structural limitations or because randomization cannot be done for practical or (seemingly) ethical reasons. There are many examples of an unproved intervention being so widely-believed to be effective that clinical trialists and potential subjects decline randomization.