This comprehensive reference source will benefit all transplant specialists working with pharmacologic and biologic agents that modulate the immune system. Compiled by a team of world-renowned editors and contributors covering the fields of transplantation, nephrology, pharmacology, and immunology, the book covers all anti-rejection drugs according to a set template and includes the efficacy of each for specific diseases.
Blood Stem Cell Transplantation conveys the excitement that accompanies the newest developments in hematopoietic stem cell transplantation. Some of the applications that stand to impact this field most significantly are based on recent advances in the biological sciences, as demonstrated by the chapters on gene therapy, on the detection of minimal residual disease using molecular techniques, and on the use of radioimmunoconjugates targeting lymphoma and leukemia-associated antigens. Others are the results of clinical observations - e.g., the association between graft-versus-host- disease (GVHD) and durable remissions that have led to creative clinical experiments such as donor leukocyte infusions (DLI). Attempts to unravel the biological events that underlie the responses seen in patients with relapsed chronic myelogenous leukemia treated with DLI are likely to provide the basis for future refinements in this clinical approach. Hopefully, improved response rates and reduced toxicity will result. The power of the immunologic response in controlling malignant disease is underscored in the chapter on post-transplant immunotherapy. The complex immunologic process that results in clinical GVHD may be dissected and engineered to provide clinical benefits that include, in addition to its antineoplastic effects, the amelioration of its clinical manifestations. Better control of GVHD with less global immunosuppression will facilitate the use of mismatched and unrelated donors. This area of investigation perfectly illustrates the continued interplay between the laboratory and the clinic. The continued cross-fertilization of ideas between immunologists, molecular biologists and clinical investigators is likely to yield important advances in this field for years to come. Possible applications of stem cell transplantation continue to grow with the identification of alternative sources of stem cells and the potential to engineer and/or expand the graft. Although the use of unrelated and mismatched donors continues to increase, the possibilities associated with umbilical cord blood transplantation are legion, especially if stem cells can be expanded ex vivo to provide grafts for full-sized adults. Using techniques in which contaminating malignant cells may be eliminated from autografts through positive selection, autologous transplantation may prove highly effective, especially when coupled with post-transplant immunotherapy. Some of these same methodologies have helped facilitate the use of autologous grafts for transplantation in patients with chronic myelogenous leukemia without allogeneic donors. Advances in the supportive care of transplant patients, including the pretransplant identification of those at risk from pulmonary complications and the use of cytokines to speed engraftment, have reduced morbidity and mortality to such a degree that it is appropriate to consider high-dose therapy and stem cell reconstitution in patients with nonmalignant diseases. The impressive advances that have occurred in transplantation for thalassemia are described by pioneers in their area of investigation. The burgeoning field of transplantation for autoimmune disorders, including its immunobiologic basis and soon-to- be-realized clinical potential, is also summarized. Continued progress in the use of high-dose therapy with stem cell rescue for the treatment of pediatric tumors, which derives in part from improved supportive care, is detailed. The sobering voice of the health care economists underscores the necessary limitations to our seemingly unbridled imagination. Cost- consciousness and financial know-how will need to be reflected in future study designs. Given the seemingly endless applications of our technology, strategies to insure its cost-effectiveness will be necessary. Continued financial support for laboratory investigation and for the clinical experiments they generate will be required if we are to go forward. Blood Stem Cell Transplantation lays the foundation for many of these future advances; it is incumbent upon us all to insure its realization.
Cell therapy is a rapidly developing area, drawing on cell biology, molecular biology, virology, immunology, cell quantitation techniques and biomedical engineering. It has potential in many clinical settings, in the treatment of cancer and other diseases. This volume in the series Cancer: Clinical Science in Practice examines the current state and future prospects of cell therapy, which seems likely to have an even more profound impact on health care than did the production of proteins by recombinant DNA technology. The coverage is broad, including the scientific principles of haematopoietic cell therapy, the technology of cell collection and preparation, current and likely future clinical applications of cell therapy, and the principles and practice of cellular immunotherapy. Up-to-date and authoritative, volumes in this series are intended for a wide audience of clinicians and researchers with an interest in the applications of biomedical science to the understanding and management of cancer.
Non-myeloablative allogeneic stem cell transplantation (also known as mini-transplantation or reduced-intensity conditioning transplantation) is a major advance in the field of hematopoietic transplantation within the last 5 years. This approach uses non-cytotoxic or reduced-intensity cytotoxic therapy to prepare patients for allografting of hematopoietic stem cells and lymphocytes. It has the potential to deliver the potent anti-tumor immunotherapy and bone marrow replacement capacity of allogeneic stem cell transplantation to patients with reduced treatment-related morbidity and mortality. It may also enable allogeneic transplantation in patients who would be considered ineligible for conventional transplants because of co-morbidity or advanced age. However, this approach may necessitate more careful monitoring of post-transplant chimerism and malignant disease-status than is usual with conventional allografting. There is also controversy regarding the best preparative regimen and graft-versus-host disease prophylaxis to use.
Some three decades after bone marrow transplantation was introduced in the field of hematology and oncology, transplantation today continues to rapidly grow and expand into a variety of new modalities. Peripheral blood has been established as an effective source of autologous progenitor cells. Furthermore, the graft-versus-leukemia effect has resulted in novel strategies of adoptive immunotherapy for cancer. Finally, approaches to gene transfer and therapy are utilizing transplantation methodologies and can augment their effects. Current results, new developments and perspectives are presented in this volume. Conventional and innovative experimental approaches, the past and the future of bone marrow transplantation are reviewed and discussed by leading representatives.
This book describes how the Jerne-Burnet Forbidden Clone Theory and the Adams-Knight H Gene Theory, solved the pathogenesis and genetics of the autoimmune diseases showing how specific immunotherapy and prophylaxis can be developed. Furthermore, Ebringer's discovery of two microbial triggers of autoimmune diseases is described and the conclusion drawn that all autoimmune diseases have microbial triggers, so will be preventable by the finding of the triggers and vaccination against them.