Graft failure is a group of complications after allogeneic hematopoietic stem cell transplantation, which occurs according to different data up to 30%. The group of complications includes primary and secondary graft failure, primary, secondary and transient poor graft function and graft rejection. Diagnostic difficulties consist in the lack of unified diagnostic criteria accepted in the transplantation community and in the dual interpretation of these complications according to the foreign literature. The purpose of this literature review was to identify the most common criteria of different types of graft failure and determine the tactics of diagnosis and treatment. In this review we analyzed data from various literature sources, gave definitions of graft failure and poor graft function. We analyzed the literature data on the methods used to treat these conditions.
Introduction. Natural killers are the "first line" of antitumor and antiviral protection in the early stages after аllogeneic hematopoietic stem cell transplantation. Quantitative characteristics reach normal values already in the first month after the infusion of blood stem cells to the recipient. Self-tolerance of natural killers is achieved due to many receptors on their surface, but killer immunoglobulin-like receptors play a key role. Their role is to recognize "self" cells and block signals aimed at destroying their own cells. Knowledge of the functional activity of natural killers urged to studying the impact of mismatches between the inhibitory receptor gene and the ligand on the development of allogeneic hematopoietic stem cell transplant failure.The aim of research was to study the probability of the graft failure development in allogeneic hematopoietic stem cell transplantation depending on the recipient's killer immunoglobulin-like receptor genotype.Material and methods. Genotyping of killer-cell immunoglobulin-like receptors in 66 recipients of blood stem cells by the polymerase chain reaction method was performed in the study. Using an online calculator, receptors were classified as "best", "better" and "neutral" depending on the genotype. The end point of the assessment was the development of graft failure in the presence of different genotypes of immunoglobulin-like receptors in the recipient.Results. According to the data obtained, the presence of the “best” and "better" killer-cell immunoglobulin-like receptor genotype in the recipient significantly increased the risks of developing various forms of graft failure.Conclusion. The presence of the KIR2DL3 genotype in a recipient of hematopoietic stem cells significantly (by 3 times) reduces the likelihood of primary graft failure. This result is of great prognostic significance, although at present no ways of influencing it have been developed. The presence of the “best” killer immunoglobulin-like receptors genotype in the recipient increases the likelihood of developing graft failure by more than 3 times compared to the best and neutral genotype (44.4% vs. 13.4%).
Transplantation allows us to confidently save the lives of previously doomed patients. Unfortunately, this colossal achievement of human progress has a problematic side – the shortage of donor organs. The use of animal organs could solve it. Currently, the issues of xenotransplantation have become relevant again after the experimental xenotransplantation of the kidney of a genetically modified pig in 2021, and the xenotransplantation of the heart in 2022. This practice raises a number of ethical questions. Is it ethical to put humanity at risk by saving one person? Is it ethical to limit the civil rights of a xeno-recipient? Will xenotransplantation create another reason for discrimination? Can the creation of xenochimeras be considered an unacceptable interference in the Divine plan from a religious point of view? Is it ethical to use higher animals for xenotransplantation? Will an increase in the number of xenotransplants create a risk of the identity of the human race? Will xenotransplantation create new questions about equitable organ allocation? The sources of scholars of theologians related to the main Abrahamic religions on this topic are analyzed. Consideration of theological approaches to the new ethical problems presented by xenotransplantation does not allow us to find a unanimity of opinion. However, as this new branch of medical science makes concrete clinical progress, the attitude of society, religious leaders and ordinary believers towards it will improve. From an individual point of view, Judaism does not object to xenotransplantation to prolong and save human life, even in the case of non-kosher animals with genetic modifications. The preservation of life outweighs other values almost without exception. Xenotransplantation, even from a pig, is hailed as a life-sustaining medical intervention from a Jewish ethical perspective by most authors. In Christianity, the motivation is to try to follow the example of Jesus Christ in bringing healing to all those in need. While physiological healing is important, the ultimate goal is the overall well-being of the individual, which requires spiritual, mental, and social well-being in addition to physical health. The most correct generalization about Islamic bioethical views on xenotransplantation would be that, given the state of science, the final ethical and legal definition remains ambiguous, but in general, xenotransplantation as a means of saving human life may be acceptable.
The graft-versus-host disease (GVHD) is among the most common complications after hematopoietic stem cell transplantation (allo-HSCT). The main tools for GVHD prevention remain calcineurin inhibitors (cyclosporin A, tacrolimus), methotrexate, mycophenolate mofetil. Upon implementation of reduced-intensity conditioning regimens, antithymocyte globulin was widely introduced. However, negative effects upon reconstitution of T-cell immunity have been noted, thus increasing risk of severe infectious complications and disease relapse. With extended practice of HSCT from alternative (partially matched or haploidentical) donors, cyclophosphamide was increasingly used. Our aim was to study reconstitution of immune cell subpopulations in the patients undergoing bone marrow transplantation (BMT), when using different GVHD prophylaxis regimens, including the schedules with post-transplant CP usage. The study concerned 44 cases classified into 2 groups. The first one included patients with standard immunosuppressive therapy, antithymocyte therapy, cyclosporine A, methotrexate, mycophenolate mofetil. The second group included the patients who received CP as immunosuppressive drug combined with other treatments (cyclosporine A, methotrexate, mycophenolate mofetil). At specified control terms, (D+14, +30, +60, +90) the blood leukocyte subpopulations were assayed by means of multicolor flow cytometry. Absolute counts of CD4+ cells in HSCT recipients treated with CP post-BMT proved to be sufficiently lower at D+14 and +30, than in those treated with classical immunosuppressive therapy. However, at later terms, (D+60, +90), these differences were not observed. Moreover, in CP-treated bone marrow recipients, absolute numbers of CD8+ cells was significantly higher, compared to the patients who received conventional GVHD prophylaxis. Reconstitution of the studied lymphocyte populations in hematopoietic cell recipients did not depend on the GVHD prophylaxis regimen. Usage of CP combined with bone marrow as a source of stem cells, brings about sufficient decrease of some cell populations (CD4+; CD8+; NK cells) at early terms post-transplant. Administration of CP combined with hematopoietic stem cells as the source of hematopoietic graft seems to be more reasonable.
In this study, we analyzed technologies for obtaining, processing, segmentation, and transmitting of microphotographs for subsequent recognition. We selected the most promising machine learning algorithms optimal for the processing of medical images, investigated the technologies of analyzing medical texts, studied the aspects of using the Watson neural network for analyzing the semantics of medical images, as well as the aspect of using the unified medical language UMLS for the needs of syndromic diagnostics for the evaluation of medical texts from medical histories in natural language. We also developed an interface for receiving, processing, segmenting, and transmitting microphotographs to artificial neural networks and an interface for the primary accepting and processing of microphotographs based on the OMERO medical image processing platform. To send data online, a demo script for jupiter was prepared. An interface for transmitting medical texts to the medical text semantics recognition system was also developed. The IBM Watson Annotator for Clinical Data was used to perform preliminary analysis of medical texts. We created a database of medical images of the bone marrow for neural network training. We made 3,500 color microphotographs (600 × 400 pixels) of bone marrow smears at a resolution of × 600 (light microscopy; hematoxylin and eosin staining). We performed marking of 11 types of bone marrow cells. We created a database of medical texts (167 patients, 40,000 words) to prepare a neural network. The database was stripped of all personal identifiers.
The aim of this work is to provide basic answers to questions related to the vaccination of solid organ transplant recipients based on the latest literature sources and clinical guidelines. Vaccination of solid organ transplants and persons in constant contact with them is a mandatory measure, the provision of which is a vital measure that effectively reduces the risk of death from COVID-19. Doubts about less effectiveness in conditions of immunosuppression or the potential risk of developing adverse reactions are significantly inferior to the risk of death and the development of severe complications. Until new data become available, the vaccination regimen must strictly comply with the instructions for medical use of the drug. Before transplantation, the patient should be examined according to the screening protocol, and also consulted by the transplant doctor who supervises him. It is possible that whole virion vaccines (CoviVac) have an advantage over others when vaccinating solid organ recipients, but clinical experience in this matter has not yet been obtained.
In memory of academician V.G. Savchenko, who made an invaluable contribution to the development of the program bone marrow transplants both in Russia and in the Samara region.
Changes in current scientific literature and regulatory documents related to the issues of infectious safety in organ and tissue donation have been analyzed. The suggestions have been given for changing the existing practices to meet new challenges. Data on threats to the safety of organ and tissue donation associated with the COVID-19 pandemic have been presented.
Coronavirus 2019 (COVID-19) is a severe acute respiratory infection (TORI) caused by the new coronavirus SARS-CoV-2. The SARS-CoV-2 virus is a single-stranded stranded RNA virus with nucleocapside. Sequencing of its complete genome has shown that it is closely related to SARS-CoV, with which it shares about 79 % of its genome. The article describes the pathogenesis of COVID-19 and potential approaches to treating patients as well as approaches to patient management after transplantation with COVID-19.
Changes in current scientific literature and regulatory documents related to the issues of infectious safety in organ and tissue donation have been analyzed. The suggestions have been given for changing the existing practices to meet new challenges. Data on threats to the safety of organ and tissue donation associated with the COVID-19 pandemic have been presented.
The epidemiological situation with tuberculosis in Russia continues to be strained. The issues of accurate diagnosis and treatment remain unsolved; these issues are particularly urgent for the patients after solid organ transplantation because of a higher risk of the disease development while on drug immunosuppression. This article has described the clinical case of a patient with a clinical presentation of disseminated pulmonary tuberculosis that emerged in a steroidresistant rejection. The issues of drug therapy and drug interactions with anti-tuberculosis and immunosuppressive agents have been discussed.