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Current Opinion in Hematology Jan 2016Neutropenia absolute neutrophil count (ANC) less than 1.5 × 10(9)/l is a common hematological finding, and severe neutropenia, that is, ANC less... (Review)
Review
PURPOSE OF REVIEW
Neutropenia absolute neutrophil count (ANC) less than 1.5 × 10(9)/l is a common hematological finding, and severe neutropenia, that is, ANC less than 0.5 × 10(9)/l is a well known risk factor for susceptibility to bacterial infections. This review provides a succinct clinical approach to the diagnosis and treatment of neutropenia with specific recommendations on the treatment of severe chronic neutropenia with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF).
RECENT FINDINGS
Experts agree that patients with acute febrile neutropenia should be treated with antibiotics and that patients at high risk of severe neutropenia (>20% risk) after myelosuppressive chemotherapy should be treated prophylactically with a myeloid growth factor, usually G-CSF. The diversity of causes and consequences of chronic neutropenia make the diagnosis and management of these patients more complicated.
SUMMARY
The review provides a stepwise approach to neutropenia focusing first on reaching a provisional diagnosis and treatment plan then steps to a final diagnosis. It also provides specific recommendations on the treatment of severe chronic neutropenia with G-CSF.
Topics: Humans; Neutropenia
PubMed: 26554885
DOI: 10.1097/MOH.0000000000000208 -
Cell Jan 2018Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus...
Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. Therefore, modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity, which to date, was considered to involve functional changes of mature myeloid cells in the periphery.
Topics: Animals; Cells, Cultured; Granulocyte-Macrophage Colony-Stimulating Factor; Immunity, Innate; Immunologic Memory; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; Myeloid Progenitor Cells; Myelopoiesis; beta-Glucans
PubMed: 29328910
DOI: 10.1016/j.cell.2017.11.034 -
Antimicrobial Agents and Chemotherapy Aug 2019Linezolid is administered as a fixed dose to all patients despite evidence of increased exposure and myelosuppression in renal impairment. The objectives of these...
Linezolid is administered as a fixed dose to all patients despite evidence of increased exposure and myelosuppression in renal impairment. The objectives of these studies were to assess the risk of thrombocytopenia with standard-dose linezolid in renal impairment and to identify an alternate dosing strategy. In study 1, data from adult patients receiving linezolid for ≥10 days were retrospectively reviewed to determine the frequency of thrombocytopenia in patients with and without renal impairment. Time-to-event analyses were performed using Cox proportional-hazards models. In study 2, population pharmacokinetic modeling was employed to build covariate-structured models using an independent data set of linezolid concentrations obtained during routine therapeutic drug monitoring (TDM). Monte Carlo simulations were performed to identify linezolid dosing regimens that maximized attainment of therapeutic trough concentrations (2 to 8 mg/liter) across various renal-function groups. Toxicity analysis (study 1) included 341 patients, 133 (39.0%) with renal impairment. Thrombocytopenia occurred more frequently among patients with renal impairment (42.9% versus 16.8%; < 0.001), and renal impairment was independently associated with this toxicity in multivariable analysis (adjusted hazard ratio [aHR], 2.37; 95% confidence interval [CI], 1.52 to 3.68). Pharmacokinetic analyses (study 2) included 1,309 linezolid concentrations from 603 adult patients. Age, body surface area, and estimated glomerular filtration rate (eGFR) were identified as covariates of linezolid clearance. Linezolid dose reductions improved the probability of achieving optimal exposures in simulated patients with eGFR values of <60 ml/min. Thrombocytopenia occurs more frequently in patients with renal impairment receiving standard linezolid doses. Linezolid dose reduction and trough-based TDM are predicted to mitigate this treatment-limiting toxicity.
Topics: Anti-Bacterial Agents; Area Under Curve; Drug Monitoring; Female; Glomerular Filtration Rate; Humans; Linezolid; Male; Middle Aged; Monte Carlo Method; Renal Insufficiency; Retrospective Studies; Thrombocytopenia
PubMed: 31109977
DOI: 10.1128/AAC.00605-19 -
Oncology Letters Jul 2018Cancer remains one of the most common causes of mortality globally. Chemotherapy, one of the major treatment strategies for cancer, primarily functions by targeting the... (Review)
Review
Cancer remains one of the most common causes of mortality globally. Chemotherapy, one of the major treatment strategies for cancer, primarily functions by targeting the cancer cells and affecting them physiologically, but also affects normal cells, which is a major concern at present. Therefore, adverse effects of chemotherapy drugs, including myelosuppression and liver and kidney damage, are of concern. Now, microbial products have attracted attention in cancer treatment research. Notably, carcinogenesis is considered to be associated with microbial dysbiosis, particularly the positive antitumor effects of bifidobacteria. Although there remains a substantial amount to be understood about the regulation of bifidobacteria, bifidobacteria remain an attractive and novel source of cancer therapeutics. The present review focuses on introducing the latest information on the antitumor effects of bifidobacteria and to propose future strategies for using bifidobacteria in the development of cancer therapeutics.
PubMed: 29963126
DOI: 10.3892/ol.2018.8692 -
Journal of Cancer Research and... 2016Oxaliplatin (1, 2-diamminocyclohexaneoxalato-platinum) is a novel platin analog, which is widely used in gastrointestinal malignancies. Platinum analogs damage cellular... (Meta-Analysis)
Meta-Analysis Review
Oxaliplatin (1, 2-diamminocyclohexaneoxalato-platinum) is a novel platin analog, which is widely used in gastrointestinal malignancies. Platinum analogs damage cellular deoxyribonucleic acid (DNA) by leading covalent bifunctional DNA adducts with cellular DNA. Major side effects of oxaliplatin are neurotoxicity (peripheral neuropathy), myelosuppression with moderate thrombocytopenia and gastrointestinal toxicity (diarrhea). Thrombocytopenia might be related to myelosuppression and/or drug-induced immune thrombocytopenia (DIIT). In here, oxaliplatin-induced thrombocytopenia is discussed with review of the literature.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Gastrointestinal Neoplasms; Humans; Organoplatinum Compounds; Oxaliplatin; Thrombocytopenia
PubMed: 27461601
DOI: 10.4103/0973-1482.154056