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Haematological Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Many malignant blood diseases are curable. Acute lymphoblastic leukaemias (ALL) in children and HL in young adults are both highly curable with long-term remissions in over 90% of patients in these groups. Remission rates are dependent on patient factors (e.g. comorbidities and ability to tolerate intensive therapy) and disease biology (e.g. cytogenetic risk group, stage). Furthermore, many haematological malignancies are curable with allogeneic haematopoietic stem cell (HSC) transplantation, but in the over 60s this mode of treatment is high risk, carrying a transplant-related-mortality risk of up to 30% or more.
AI and Autoimmunity
Published in Louis J. Catania, AI for Immunology, 2021
Hematopoietic stem cell therapy (a “blood stem cell” that can develop into all types of blood cells found in the peripheral blood, the bone marrow, and immune cells)50 is now being used effectively (regenerative medicine) to grow new cellular and immunological based strategies for patients with malignancy and hematological disorders produced or provoked by immunologic or autoimmunologic causes. Stem cells can be readily harvested from bone marrow and adipose tissue (and other bodily tissues) and converted into undifferentiated induced pluripotent cells (iPSC – reprogrammed embryonic-like cells capable of developing into any type of human cell, a 2012 Nobel Prize award winning technology) suitable for transplantation into diseased and degenerated organs and body structures (e.g., diabetes, osteoarthritis, etc.). These cells then regenerate and begin to replace the abnormal cells with new, normal cells including immune system cells, and even potentially with functioning organs (organ morphogenesis).51 (Figure 4.2) Currently, muscle and bone tissue are particularly responsive to stem cell regeneration.
Actions of Dopamine on the Skin and the Skeleton
Published in Nira Ben-Jonathan, Dopamine, 2020
Bone is a metabolically active tissue composed of several cell types, including osteoblasts, osteocytes, and osteoclasts. Osteoblasts are involved in the creation and mineralization of bone tissue while osteocytes are mostly inactive, and are in contact with other cells in the bone through gap junctions. Osteoclasts are responsible for the breakdown of bone by the process of bone resorption. Osteoblasts and osteocytes are derived from osteoprogenitor cells. They are connective tissue cells found at the surface of bone, which can be stimulated to proliferate and differentiate. Osteoclasts are large, multinucleate cells formed through the fusion of precursor cells. They are derived from a monocyte stem-cell lineage and similar to macrophages have phagocytic properties. As discussed in Chapter 9, the bone marrow contains hematopoietic stem cells which give rise to white blood cells, red blood cells and platelets.
The impact of centralised care of younger AML patients on treatment results: a retrospective analysis of real-world data from a national population-based registry
Published in Acta Oncologica, 2021
Lukas Semerad, Zuzana Sustkova, Petr Cetkovsky, Pavel Jindra, Zdenek Koristek, Jan Novak, Zdenek Racil, Tomas Szotkowski, Barbora Weinbergerova, Pavel Zak, Zdenek Pospisil, Jana Baranova, Jiri Mayer
The care for younger patients with acute myeloid leukaemia (AML) requires fully equipped medical facilities that have routine experience with the management of this aggressive disorder. Two independent analyses of real-world data from the United States (US) have showed a lower early mortality after an intensive chemotherapy when the patients are treated in high-volume centres or in National Cancer Institution-Designated Cancer Centres (NCI-CC) compared to the treatment in low-volume or in non-NCI-CC centres [1,2]. The size and experience of the centre has also a statistically significant effect on early mortality after allogeneic transplantation of haematopoietic stem cells (HSCT), as shown by a US study where a lower 100-day mortality after allogeneic HSCT at centres with a higher patient-per-physician ratio was observed [3]. These results were confirmed by a retrospective analysis of the European Group for Blood and Marrow Transplantation (EBMT), in which 100-day survival after unrelated allogeneic HSCT was improved at centres performing ≥ 20 transplants per year [4]. The reduction in mortality is probably related to a better management of serious complications that require an intensive supportive care. Ross et al. showed a lower 30-day mortality for three common medical conditions, including pneumonia and heart failure, when treated in higher-volume hospitals [5].
Successful treatment with cyclosporine and anti-tumour necrosis factor agent for deficiency of adenosine deaminase-2
Published in Scandinavian Journal of Rheumatology, 2021
D Keino, K Kondoh, Y Kim, A Sudo, R Ohyama, M Morimoto, H Nihira, K Izawa, S Iwaki-Egawa, T Mori, A Kinoshita
Deficiency of adenosine deaminase-2 (DADA2) is an autoinflammatory disease caused by loss-of-function homozygous or compound heterozygous mutations in CECR1 (cat eye syndrome chromosome region 1) (1, 2). The phenotype of DADA2 is widely heterogeneous, with a variable age of onset. Manifestations include fever, early-onset lacunar stroke, livedo, nodular vasculitis, immunodeficiency, pure red cell aplasia (PRCA), cytopenia, and hypogammaglobulinaemia. Treatment mainly consists of anti-tumour necrosis factor (anti-TNF) agents. Cyclosporine (CyA), tacrolimus, and azathioprine have all been used, with little success (1, 2). Although anti-TNF agents prevent strokes and improve the manifestations of vasculitis in DADA2, their efficacy for treating PRCA and bone marrow failure is less clear (3). Haematopoietic stem cell transplantation may be considered for patients with severe haematological presentations (4).
Expression profile analysis reveals hub genes that are associated with immune system dysregulation in primary myelofibrosis
Published in Hematology, 2021
Haotian Ma, Jincen Liu, Zilong Li, Huaye Xiong, Yulei Zhang, Yanping Song, Jianghua Lai
Blood cell development initiates from haematopoietic stem cells (HSCs). HSCs can differentiate into a multi-lineage committed progenitor cells, such as common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs). CMPs give rise to the myeloid lineage, including erythrocytes, some leukocytes and megakaryocytes that produce platelets; cells belonging to the lymphoid lineage (white blood cells, leukocytes, NK cells, T and B lymphocytes) are differentiated from CLPs. At each stage, multiple genes perform different functions within the differentiation procedure (Figure 6a). Haematopoiesis is orchestrated via a tightly regulated network. Haematopoiesis homeostasis is important, and the imbalance between cells, genes and the microenvironment could induce the relevant disruption to contribute to some haematological diseases, more specifically, myeloproliferative disorders [19,20].