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Retroviral Gene Transfer in Autologous Bone Marrow and Stem Cell Transplantation
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Rafat Abonour, Kenneth Cornetta
In the allogeneic setting, transplanted progenitors cells are most often infused immediately after processing, while autologous cells are usually stored in liquid nitrogen until the patient has completed chemotherapy and/or radiation therapy. Both types of cells are infused intravenously and home to the bone marrow microenvironment, where they restore granulopoiesis in approximately two weeks, with platelet and red cell counts returning within approximately one month.
The lymphoreticular system and bone marrow
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
A decreased neutrophil count (neutropenia) or complete lack of neutrophils (agranulocytosis) may be due to decreased myelopoiesis or excessive destruction of white cells. Both conditions are associated with a risk of infection. Often, there is concomitant reduction in other blood cells (pancytopenia), but isolated neutropenia can occur. Neutropenia through insufficient production is most commonly drug induced (cytotoxic drugs, chloramphenicol, chlorpromazine, sulphonamides, and phenylbutazone). Neutropenia complicates aplastic anaemia and marrow replacement by malignant and non-malignant processes. Megaloblastic anaemias and myelodysplastic syndromes lead to inefficient granulopoiesis. Some infections (e.g. HIV) appear to suppress normal myelopoiesis.
Unexplained Fever In Hematologic Disorders Section 1. Benign Hematologic Disorders
Published in Benedict Isaac, Serge Kernbaum, Michael Burke, Unexplained Fever, 2019
In addition to the humoral inhibition of granulopoiesis, there is also a cellular mechanism: hemopoietic inhibitory T-cells were found, especially in patients with rheumatoid arthritis, Felty’s syndrome, chronic hepatitis and other autoimmune diseases, and in myeloproliferative disorders.20 Immune mechanisms are also found in some drug-induced neutropenias (see above).
Increased levels of low density neutrophils (LDNs) in myocardial infarction
Published in Acta Cardiologica, 2023
Jacquelina Y. T. Yiu, Kathryn E. Hally, Peter D. Larsen, Ana S. Holley
We postulate here that LDNs represent an immature, hyperactivated neutrophil subset that appears in circulation at a greater frequency in MI subjects due to emergency granulopoiesis. In this study, we utilised CD33 and CD16 to capture neutrophil maturation [17,36]. More specifically, upregulation of CD33 is a hallmark of immaturity, while upregulation of CD16 is a hallmark of maturity [32]. In our study, the expression of CD33 was found to be significantly higher in LDNs than NDNs and, conversely, CD16 showed the reciprocal expression pattern. As such, LDNs are CD33highCD16low compared to CD33lowCD16high NDNs. Together, these observations support the view that LDNs are immature cells [37]. Interestingly, we note at least some patients appeared to show an increase in CD16 expression in MI-associated LDNs, compared to the level observed in healthy LDNs. This may indicate that some functional pathways are different in inflammatory-associated LDNs, although we are not able to confirm if this is the case in this study.
A mini-review on aplastic anemia, illustrated by a case report on bone marrow hot pockets mimicking sclerotic bone metastases
Published in Acta Clinica Belgica, 2022
Emilie Janssens, Jo Van Dorpe, Vanessa Van Hende, Ine Moors, Philip Vlummens, Ciel De Vriendt
A 61-year-old, previously healthy female presented herself at primary care in April 2019 with exertional dyspnoea and fatigue. She reported no bleeding diathesis nor infections. Peripheral blood examination showed pancytopenia with a hemoglobin of 7.6 g/dL, a platelet count of 26.000/µL and a leukocyte count of 2.100/µL with 25.4% neutrophils, 67.8% lymphocytes, 6.3% monocytes and 0.01% eosinophils. No iron, folate or vitamin B12 deficiency was apparent. The patient was subsequently referred to a hematology department, where the aberrant blood counts were indeed confirmed. Bone marrow aspirate from the iliac crest showed a moderately cellular marrow with a dysplastic erythroid lineage and very poor megakaryo- and granulopoiesis. There was no excessive amount of blasts. Due to dysplastic changes, differentiation between hypoplastic myelodysplastic syndrome (MDS with unilineage dysplasia) and AA was difficult. Microscopic evaluation of the trephine biopsy revealed a profoundly hypocellular marrow with rare hematopoietic elements (Figure 1). Megakaryocytes were shown to be absent. No excessive blasts, nor malignant infiltrations were detected. Conventional karyotyping was normal and an NGS panel for gene mutations associated with AML (ASXL1, CEBPa, DNMT3A, FLT3, IDH1, IDH2, KIT, NPM1, NRAS, RUNX1, TET2, U2AF1, SF3B1, SRSF2, TP53) could not find any mutations.
Modeling approaches for reducing safety-related attrition in drug discovery and development: a review on myelotoxicity, immunotoxicity, cardiovascular toxicity, and liver toxicity
Published in Expert Opinion on Drug Discovery, 2021
Elena M. Tosca, Roberta Bartolucci, Paolo Magni, Italo Poggesi
The G-CSF effect was also modeled in [62]. In this work, Chen et al. developed a physiological model of granulopoiesis incorporating the drug mechanism of action on the proliferating BM progenitor cell cycle, as determined from in vitro BM studies. The physiological drug-independent granulopoiesis model was developed on previously published studies in healthy volunteers and is composed by three subsystems representing i) proliferation, differentiation, maturation and mobilization of neutrophils in the BM; ii) circulating and marginated neutrophils and iii) the kinetics and action of G-CSF support therapies. The model was used to predict the time course of absolute neutrophil count and the neutropenia incidence observed in three previously reported clinical trials showing the ability to predict grade 3 and 4 neutropenia with good accuracy.