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The Host Response to Grafts and Transplantation Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Bone marrow transplantation, which has enormous clinical potential, is still under development and has been increasingly successful. Bone marrow transplantation is most successful when the donor and recipient are completely histo-compatible. Bone marrow transplantation is an immunologically unique procedure, and has a variety of correspondingly unique complications. For this technically simple transplant procedure, bone marrow is aspirated by needle from the pelvis or sternum of the graft donor, and transfused into a recipient that has been made immunodeficient by lethal irradiation or chemical preconditioning. Complications arise when immunocompetent lymphoid cells in the donor bone marrow recognize the foreign histocompatibility antigens of the immunocompromised recipient and initiate a rejection response, resulting in a potentially fatal attack on the host by the graft (graft-versus-host disease). Bone marrow recipients are also often severely immunocompromised and are thus susceptible to opportunistic pathogens.
On patients’ difficulties in understanding medical risks and the aims of clinical risk communication
Published in Ulrik Kihlbom, Mats G. Hansson, Silke Schicktanz, Ethical, Social and Psychological Impacts of Genomic Risk Communication, 2020
The starting point of my discussion will not be a theoretical account, such as the one suggested by Beauchamp and Childress. I start by examining how patients understand risk as expressed by haematologists. Haematologists are concerned that newly diagnosed patients may have a difficult time really understanding the severe side-effects of certain treatments. My starting point is material collected in a pilot interview study with eight haematologists at Uppsala University Hospital and Karolinska University Hospital, Sweden, performed by the present author in spring 2016. The interview guide consisted of questions that addressed three themes: risk information, directiveness and relatives. The participants related that leukaemia patients had a difficult time understanding the possible side-effects of bone marrow transplantation. As can be seen in Table 5.1, the haematologists also thought that in most cases they should be direct and use qualitative statements such as ‘low risk’ and ‘very high risk’. This direct approach, however, is not shared by genetics counselling where it is often suggested to be non-direct with patients (Wolff and Jung, 1995). Moreover, the use of qualitative rather than quantitative risk estimates may be in conflict with the evidence of how to best communicate risk. I will return to both of these themes at the end of the chapter as they seem to relate to the first theme in a significant way.
Monoclonal Antibodies as Agents to Purge Tumor Cells from Bone Marrow: Laboratory and Clinical Experiences
Published in John T. Kemshead, Pediatric Tumors: Immunological and Molecular Markers, 2020
In recent years, there has been a dramatic increase in the use of bone marrow transplantation for the treatment of a variety of diseases, particularly refractory cancer.1 The feasibility of transplanting marrow for hematological reconstitution was first demonstrated in the early 1950s,2 and to date, more than 11,000 patients have been treated. About three quarters of these procedures have been carried out since 1983.1 In the treatment of malignant diseases, bone marrow transplantation has been used extensively as rescue, following marrow-ablative high dose therapy for refractory leukemia, lymphoma, and certain solid tumors. An impediment to its more extensive application has been the scarcity of suitable tissue-matched normal marrow donors. Within the immediate family of a patient, the probability of finding a match is one in four, although in practice, this chance is closer to one in three,3 since patients usually have multiple siblings. The probability of finding a donor in the general population is correspondingly smaller,4 even if the HLA-typing information was readily available. Two approaches are being used to circumvent this scarcity. The first is the use of mismatched marrow.3,5
The successful strategy of comprehensive pre-implantation genetic testing for beta-thalassaemia–haemoglobin E disease and chromosome balance using karyomapping
Published in Journal of Obstetrics and Gynaecology, 2022
Sirivipa Piyamongkol, Suchada Mongkolchaipak, Pimlak Charoenkwan, Rungthiwa Sirapat, Wanwisa Suriya, Tawiwan Pantasri, Theera Tongsong, Wirawit Piyamongkol
Haemoglobin E disease, c.26G>A variant of beta-globin gene, is the commonest haemoglobinopathy in Asia (Fucharoen and Weatherall 2012). When this haemoglobin E gene is inherited together with a beta-thalassaemia gene a compound heterozygote is generated, specifically one with beta-thalassaemia–Hb E disease with severe anaemia. beta-Thalassaemia–Hb E disease contributes to approximately half of all cases of severe beta-thalassaemia syndrome worldwide (Than et al. 2005). In Thailand, between 30 and 50% of the population are thalassaemia carriers, i.e. around 24 million, with 600,000 existing patients (Chaibunruang et al. 2018). Continuous blood transfusion is needed in cases of severe thalassaemia; however, these lead to iron overload which potentially damages multiple organs and reduces the quality of life and life expectancy. Iron chelator therapy can prolong life expectancy but has significant side effects. Bone marrow transplantation and gene therapy are the present ultimate options with high levels of expenditure and risk of complications (Caocci et al. 2017).
Neuro-Ophthalmic Literature Review
Published in Neuro-Ophthalmology, 2022
David A. Bellows, John J. Chen, Jenny A. Nij Bijvank, Michael S. Vaphiades, Xiaojun Zhang
The authors report a 30-year-old woman with a previous history of remitted acute lymphoblastic leukaemia (ALL) who presented with a 1-week history of floaters in her right eye. Her ophthalmological examination showed remarkable optic disc swelling in both eyes. She was diagnosed with an ALL relapse presenting as bilateral optic nerve leukaemic infiltration. Local radiotherapy was planned for both eyes, however, due to efficient recovery with chemotherapy, it was cancelled. Allogenic bone marrow transplantation was subsequently performed. Leukaemia relapse in the central nervous system is a sign of a poor prognosis and requires prompt treatment. It is hypothesised that the blood-brain barrier limits the delivery of chemotherapeutic drugs to the eye and infiltration of the optic nerve by leukaemic cells might prejudice the flow of cerebrospinal fluid between the cranial space and the optic disc. This paper addresses the action of chemotherapeutic drugs on ocular tissues and reinforces the importance of ophthalmologic examination during and after treatment of leukaemia.
Estimation of the cumulative baseline hazard function for dependently right-censored failure time data
Published in Journal of Applied Statistics, 2021
Antai Wang, Xieyang Jia, Zhezhen Jin
In this section, we illustrate our methodology by analyzing a bone marrow transplantation data described in Klein and Moeschberger [11]. The dataset was collected during a study in which 137 patients were followed in their recovery from Leukemia after bone marrow transplantation. We are interested in the disease-free survival time T, i.e. the time until a relapse of leukemia. The patients were censored by two possible events: disease-free death or disease-free and alive at the end of the study. The censoring time C was defined as the time until the first of these two events happen. It is natural to believe that both T and C are positively dependent on the age X of the patient at transplantation. We categorized the age into two levels (with the median age as the cut point). After fitting a Gamma frailty model to this dataset with the categorized age, we have obtained estimates