Richard K. Burt - Böcker

The field of hematopoietic stem cell transplantation is rapidly evolving. Realization that hematopoietic stem cells give rise to the immune compartment has resulted in clinical trials of hematopoietic stem cell transplantation for patients with autoimmune diseases. Allogenic hematopoietic transplants are a form of adoptive immunotherapy resulting in beneficial graft-versus-tumour effects. Large numbers of hematopoietic cells can be collected with ease. Therefore, a renewable source of cells for ex-vivo genetic manipulations is readily available. Multiple trials combining hematopoietic transplants and gene therapy are in progress. One such application is the infusion of allogeneic lymphocytes containing a suicide gene to abort graft-versus-host disease. Hematopoietic stem cell transplantation is in reality the clinical and practical application of cellular therapy. Hematopoietic transplant physicians are by design or by practical application evolving into cell and gene therapy specialists.The excitement and enthusiasm in hematopoietic transplantation is that it offers a door to the future - a future not of drugs or titrating poisonous chemotherapy but rather of cellular and gene therapy.

This book summarizes the global progress in medical and scientific research toward converting traditionally chronic autoimmune diseases into a drug-free reversible illness using hematopoietic stem cell transplantation (HSCT) and other cellular therapies such as T regulatory cells (Treg), mesenchymal stromal/stem cells, and chimeric antigen receptor T (CAR T) cells in order to reintroduce sustained immune tolerance. This title provides information on different types of stem cells and immune cells; post-transplant immune regeneration; cellular regulatory requirements; ethical and economic considerations; and the advantages and disadvantages of HSCT in the treatment of a variety of autoimmune diseases versus current conventional treatments. Arranged by disease, the text provides a comprehensive guide to HSCT for all types of autoimmune/immune disorders including monogenetic autoimmune diseases; autoimmune aplastic anemia; neurologic immune diseases including multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, and stiff person syndrome; rheumatologic diseases such as systemic sclerosis and systemic lupus erythematosus; dermatologic diseases such as pemphigus; gastrointestinal disorders such as Crohn’s disease and celiac disease; and immune-mediated endocrinologic disease type I diabetes mellitus. Guidance is provided on the transplantation technique, cell collection and processing, conditioning regimens, infections, and early and late complications.Key FeaturesOutlines therapies and techniques for HSCT for autoimmune diseasesDiscusses the advantages of HSCT over conventional therapiesReviews the entire process of stem cell therapy from harvest and ethics to indications, efficacy, and regulatory oversight

The field of hematopoietic stem cell transplantation is rapidly evolving. Realization that hematopoietic stem cells give rise to the immune compartment has resulted in clinical trials of hematopoietic stem cell transplantation for patients with autoimmune diseases. Allogeneic hematopoietic transplants are a form of adoptive immunotherapy resulting in beneficial graft versus tumor effects. Large numbers of hematopoietic cells can be collected with ease. Therefore, a renewable source of cells for ex vivo genetic manipulations is readily available. Multiple trials combining hematopoietic transplants and gene therapy are in progress. One such application is the infusion of allogeneic lymphocytes containing a suicide gene to abort graft versus host disease. Hematopoietic stem cell transplantation is in reality the clinical and practical application of cellular therapy. Hematopoietic transplant physicians are by design or by practical application evolving into cell and gene therapy specialists. The excitement and enthusiasm in hematopoietic transplantation is that it offers a door to the future. A future not of drugs or titrating poisonous chemotherapy but rather of cellular and gene therapy. 1 ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION FOR HEMATOLOGIC DISEASES Martin Korbling University o/Texas MD. Anderson Cancer Center, Houston, Texas 77030 INTRODUCTION Circulating hematopoietic stem cells have emerged as an alternative to bone marrow (BM) stem cells for allografting. For many years the reconstitutive potential of circulating stem cells was questioned; peripheral blood stem cells (PBSC) were even characterized a waste product (1).

This handbook is a therapeutic manual designed as a quick, practical guide and reference for house officers, fellows, pharmacists and nurses on the bone marrow transplant unit. Indications, complications, drug doses and approaches to clinical management problems are emphasized. Diseases requiring bone marrow transplants are reviewed along with patient evaluation, marrow processing, engraftment relapse and general patient care.

Stem cell transplantation may be complicated by treatment-related mortality and like the immune system that it regenerates has equal potential to either create and preserve or destroy. The dual nature that defines stem cells is differentiation that ultimately leads to death and self-renewal, which leads to immortality. What types of stem cells are there? How are they collected? What are their attributes and characteristics? This textbook devotes many chapters to familiarize the reader with the basic science, clinical aspects, and new questions being raised in the field of stem cell biology. Blood stem cells for tolerance and tissue regeneration are a rapidly developing research and clinical field that is being applied to autoimmune diseases. In clinical trials, autologous hematopoietic (blood) stem cells are being used to reduce the cytopenic interval following intense immune suppressive transplant regimens. While as yet not delineated, some possible mechanisms and pathways leading to tolerance after hematopoietic stem cell transplantation are suggested in these chapters. Tissue regeneration from blood stem cells is also suggested by animal experiments on stem cell plasticity or metamoirosis (i.e., change in fate) as described within this textbook. Ongoing early clinical trials on tissue regeneration from blood stem cells are described in the chapter on stem cell therapy for cardiac and peripheral vascular disease. Whether autologous hematopoietic stem cells, through the process of mobilization and reinfusion, may be manipulated to contribute to tissue repair in autoimmune diseases is a future area for translational research.Hematopoietic stem cells as a therapeutic tool to induce tolerance were first applied to human autoimmune disorders in 1996. Since then, the door has opened on trials involving numerous autoimmune diseases and allogeneic as well as autologous hematopoietic stem cells. Stem cells are becoming a new therapeutic tool to supplement or replace traditional approaches of surgery, pharmacy, and radiotherapy. As the embryonic stem cell-related ethical issues involving creation and destruction are resolved, their clinical application may follow the clinical paths, trails, and trials already being explored with hematopoietic stem cells.