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Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In the oncology setting, plerixafor works by inhibiting the alpha CXCR4 chemokine receptor, thus blocking binding of its cognate ligand stromal cell derived factor-1 (SDF-1α). SDF-1α and CXCR4 have been shown to play a role in the trafficking and homing of hematopoietic stem cells (HSC) to the marrow compartment. In the form of its zinc complex, plerixafor acts as an antagonist or partial agonist of CXCR4, and an allosteric agonist of the related CXCR7 which strongly induces mobilization of hematopoietic stem cells from the bone marrow into the bloodstream as peripheral blood stem cells. This mobilization process is important as a prelude to gathering hematopoietic stem cells for transplantation. Mobilization can also be performed using granulocyte-colony stimulating factor (G-CSF) alone but is ineffective in around 15–20% of patients. However, a combination of plerixafor and G-CSF increases the percentage of patients responding to the therapy and allows the production of enough stem cells for transplantation. In this context, it is used for patients with lymphoma and multiple myeloma.
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.
Genetic Manipulation of Human Marrow: Gene Transfer Using Retroviruses
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
Philip Hughes, R. Keith Humphries
The hematopoietic stem cell is a cell that can contribute to all hematopoietic lineages, has high proliferative potential and self-renewal capacity (see Chapter 12). In the context of bone marrow transplantation and gene therapy, such cells with the capacity for regenerating and sustaining hemopoiesis lifelong must be the ultimate target for gene transfer, although some potential applications may utilize cells that can proliferate to a limited extent, such as T cells. Although rigorous quantitative assays for stem cells are not yet available in man, it is apparent from a variety of murine and human studies that these cells represent only a small fraction of marrow cells, probably less than 0.01%. In addition to their rarity, these cells are thought to normally be in a noncycling, quiescent state. Such considerations, coupled to the pluripotent properties of stem cells, place severe demands on any attempt to permanently introduce new genetic materials into hematopoietic stem cells, and to obtain appropriately regulated expression, particularly for genes for which lineage and developmentally restricted expression is desired.
Cell division cycle 37 change after bortezomib-based induction therapy helps to predict clinical response and prognosis in multiple myeloma patients
Published in Hematology, 2023
Wuqiang Lin, Xiuli Chen, Heyong Zheng, Zhenjie Cai
The mean age of enrolled multiple myeloma patients was 67.0 ± 9.2 years. There were 31 (37.8%) females and 51 (62.2%) males. Besides, 33 (40.2%) patients had renal impairment, and the left 49 (59.8%) patients did not have that. Additionally, the median (interquartile range) values of serum creatinine and beta-2-microglobulin were 1.8 (1.2–2.4) mg/dL and 5.5 (3.4–8.9) mg/L, respectively. In terms of prognostic stratification, 7 (8.5%), 34 (41.5%), and 41 (50.0%) patients were classified at International Staging System stages I, II, and III, respectively. Based on the revised International Staging System stage, 4 (4.9%), 55 (67.1%), and 23 (28.0%) patients were classified at stages I, II, and III, respectively. Regarding treatment information, 21 (25.6%) patients received the combination of bortezomib, thalidomide, and dexamethasone, 61 (74.4%) patients received the combination of bortezomib, lenalidomide, and dexamethasone. In addition, 23 (28.0%) patients received autologous hematopoietic stem cell transplantation, while 59 (72.0%) patients did not receive that. The specific information is exhibited in Table 1.
Retrospective single-center experience with OEPA/COPDAC and PET-CT based strategy for pediatric Hodgkin lymphoma in a LMIC setting
Published in Pediatric Hematology and Oncology, 2022
Achanya Palayullakandi, Amita Trehan, Richa Jain, Rajender Kumar, Bhagwant Rai Mittal, Rakesh Kapoor, Radhika Srinivasan, Nandita Kakkar, Deepak Bansal
Nine (6.3%) patients relapsed. The median duration of relapse from the initial diagnosis was 28 months; 5/9 (55.6%) patients had a late relapse. Chemotherapy administered for relapsed disease included a regimen of IEP (ifosfamide, epirubicin, and cisplatin) and ABVD to 6 (66.6%) patients. ABVD/COPP was administered to one patient due to financial constraints. One patient had a relapse in the central nervous system. He was treated successfully with MIED (methotrexate, ifosfamide, etoposide, and dexamethasone); the case was published earlier.13 RT was administered to the majority (87.5%). The median duration of follow-up from the diagnosis of relapse was 52 months. The 4-year survival with complete remission of patients with the relapsed disease was 71.1 ± 18%. Autologous hematopoietic stem cell transplant was indicated in two patients; however, it was not performed due to financial constraints.
Emerging therapies in β-thalassemia: toward a new era in management
Published in Expert Opinion on Emerging Drugs, 2020
Rayan Bou-Fakhredin, Rami Tabbikha, Hisham Daadaa, Ali T. Taher
When treating β-thalassemia, the use of autologous, and genetically modified hematopoietic stem cells (HSCs) by gene therapy provides an alternative to allogeneic HSCT. Upon the isolation of hematopoietic stem and progenitor cells (HSPCs), exogenous β- globin genes are then incorporated into the host-cell genome using a lentiviral vector [42]. These genetically modified autologous HSPCs, after full or partial myeloablation, are then returned to the patient where they repopulate in the hematopoietic compartment [42,43]. For gene therapy to be successful procedure in β-thalassemia the following are requirements: high-efficiency HSC engraftment, and gene transfer, high-level expression of β/γ-globin gene and safe expression, with minimal to no risk of insertional mutagenesis. The use of gene therapy technology has proven to be effective and curative in many animal models of β-thalassemia [44–47].