AI and Autoimmunity
Louis J. Catania in AI for Immunology, 2021
The objective of stem cell transplantation therapy is to destroy the mature, long-lived, and auto-reactive immune cells and generate a new, properly functioning immune system. The patient’s stem cells are used in a procedure known as autologous (from “one’s self”) hematopoietic stem cell transplantation (Figure 4.1). First, patients receive injections of a growth factor, which coaxes large numbers of hematopoietic stem cells to be released from the bone marrow into the bloodstream. These cells are harvested from the blood, purified away from mature immune cells, and stored. After sufficient quantities of these cells are obtained, the patient undergoes a regimen of cytotoxic (cell-killing) drug and/or radiation therapy, which eliminates the mature immune cells. Then, the hematopoietic stem cells are returned to the patient via a blood transfusion into the circulation where they migrate to the bone marrow and begin to differentiate to become mature immune cells. The body’s immune system is then restored.53
Big promise, big business
Christine Hauskeller, Arne Manzeschke, Anja Pichl in The Matrix of Stem Cell Research, 2019
The X-Cell Center (X-Cell), at the Eduardus Hospital in Cologne in Germany, first opened its doors and treating rooms to patients in 2007, later extending its operations to the Dominikus Hospital in Düsseldorf. The clinic claimed to offer treatments for patients ‘suffering from diseases for which standard medical treatment has no cure as yet’, including Parkinson’s, Alzheimer’s, cerebral palsy, multiple sclerosis, diabetes, heart disease, spinal cord injury, macular degeneration, and autism (X-Cell Center, 2007). Patients were charged between 3000 and 10 000 (EUR) per SCT. Treatments involved bone marrow extracted from the patient, the purported stem cells isolated and then administered back to the patient intrathecally (via lumbar puncture into the spinal cord), intravenously (via drip), or intramuscularly (injected into the muscles). Depending on the condition, the cells of some patients were injected directly into the brain. Whilst the use of hematopoietic stem cell transplantation, where the cells are obtained from bone marrow or cord blood, is a proven and routine treatment for some immune and blood disorders, such as acute myeloid leukaemia and lymphoma (Copelan, 2006), there is limited scientific rationale and evidence for the clinical application of bone marrow-derived stem cells for other conditions and/or diseases (Daley, 2012; Trounson and McDonald, 2015).
Precision medicine in myelodysplastic syndromes
Debmalya Barh in Precision Medicine in Cancers and Non-Communicable Diseases, 2018
MDS is rare in children, where it is more frequently associated with monosomy of chromosome 7. Adolescents with monosomy 7 frequently have (72%) GATA2 mutations and the high risk for progression to advanced disease (Wlodarski et al., 2016). Therefore, timely hematopoietic stem cell transplantation must be considered in these cases. MDS in children and young and middle aged adults is frequently associated with underlying genetic predisposition syndromes (bone marrow failure such as Fanconi anemia and dyskeratosis congenita) and nonsyndromic familial MDS/AML predisposition caused by mutations in GATA2, RUNX1, CEBPA, TERT/TERC (telomerase subunit genes), ANKRD26 (ankyrin repeat domain 26), ETV6 (gene for ETS family transcriptional repressor, variant 6), and SRP72 (signal recognition particle 72) genes (Owen et al., 2008; Godley, 2014; West et al., 2014; Babushok and Bessler, 2015; Churpek et al., 2015; Babushok et al., 2016; Bannon and DiNardo, 2016; Koeffler and Leong, 2017).
A model based on machine learning for the prediction of cyclosporin A trough concentration in Chinese allo-HSCT patients
Published in Expert Review of Clinical Pharmacology, 2023
Lin Song, Chen-Rong Huang, Shi-Zheng Pan, Jian-Guo Zhu, Zong-Qi Cheng, Xun Yu, Ling Xue, Fan Xia, Jin-Yuan Zhang, De-Pei Wu, Li-Yan Miao
We enrolled inpatients who underwent HSCT at the First Affiliated Hospital of Soochow University from January 2015 to June 2020. The inclusion criteria were as follows: (i) patients who underwent allo-HSCT, (ii) patients who were treated with CsA as a component of prophylactic immunosuppression therapy to prevent GVHD and (iii) patients with two or more TDM data for CsA after HSCT. The exclusion criteria were as follows: (i) patients whose data were incomplete, including the lack of more than 50% blood biochemical and blood routine result, the lack of demographic characteritic and diagnosis record and the lack of source of donor; (ii) CsA TDM data with concentration >1000 ng mL−1 or <30 ng mL−1; (iii) patients who underwent autologous hematopoietic stem cell transplantation (auto-HSCT); (iv) the CsA TDM data when patients were on oral CsA; and (v) patients with less than two CsA TDM data after HSCT. The flow chart of patient inclusion is shown in Figure 1. All kinds of diseases were collected in this research and classified as acute lymphoblastic leukemia, acute myelocytic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, aplastic anemia, malignant lymphoma, other nonmalignant hematological diseases, and other diseases that cannot be classified.
Hematopoietic stem and progenitor cell responses to low radiation doses – implications for leukemia risk
Published in International Journal of Radiation Biology, 2019
Nathalie Gault, Tom Verbiest, Christophe Badie, Paul-Henri Romeo, Simon Bouffler
Hematopoietic stem cell transplantation, a curative therapeutic approach for a variety of blood cell diseases such as hemoglobinopathies (Angelucci et al. 2014) and autoimmune disorders (Sullivan et al. 2010), requires a prior myeloablation. However, myeloablation using chemotherapy or radiation may cause severe short- and long-term side effects including secondary malignancy and reproductive failure and thus exclude some patients from bone marrow transplantation due to comorbid illness. For these reasons, reduced intensity conditioning regimens have been developed to achieve mild myeloablation and low toxicity. Reduced Intensity conditioning treatment currently used TBI at medium dose (2 Gy) with or without chemotherapy. This conditioning treatment induces a partial myelosuppression but TB-irradiated HSCs microenvironment at 2 Gy is modified resulting in a negative bystander effects on transplanted HSCs (Shen et al. 2012). An interesting alternative to increase bone marrow engraftment would be a 20 mGy-TBI associated with a pre-treatment of G-CSF.
Fusariosis: an update on therapeutic options for management
Published in Expert Opinion on Orphan Drugs, 2021
Laila S Al Yazidi, Abdullah M. S. Al-Hatmi
Risk factors for acquiring localized fusariosis include direct inoculation and loss of skin integrity secondary to trauma or foreign body entrance [2]. Prolonged profound neutropenia and severe T-cell immunodeficiency are the main risk factors for invasive fusariosis. The latter type of disease is limited to patients with hematological malignancy, hematopoietic stem cells, or solid organ transplant [3,9,10]. Nucci et al. reported that 56% of 84 patients with disseminated fusariosis had hematological malignancies, and 83% of them were neutropenic [9,14]. Allogenic hematopoietic stem cell transplant (HSCT) recipients are also at increased risk. The overall incidence among populations with malignancies is about six cases per 1000. The lowest risk is among autologous hematopoietic stem cell transplantation (HSCT) (1.5/1000) and the highest among mismatched related allogeneic HSCT recipients (20/1000) [9,15]. The first peak of infection is during the early pre-engraftment post-transplant period, when the patients are neutropenic. A second peak is observed among patients developing acute graft-versus-host disease (GVHD), about 70 days post-transplantation. An eventual third peak mostly involves patients with chronic extensive graft-versus-host disease (GVHD) under prolonged steroid administration, >1 year post-HSCT [9,15]. Organ transplant recipients show higher frequencies of locally invasive fusariosis compared to HSCT recipients [9,16].
Related Knowledge Centers
- Allotransplantation
- Cord Blood
- Hematopoietic Stem Cell
- Bone Marrow
- Blood
- Cancer
- Organ Transplantation
- Autologous Stem-Cell Transplantation
- Syngeneic Stem Cell Transplantation
- Twin