Hematopoietic Stem Cell Transplantation PDF

Preface

The existence of hematopoietic stem cells (HSCs) was demonstrated 40 years ago. In a seminal article published in 1961, Till and McCulloch described the presence of clonogenic bone marrow (BM) precursors that were able to reconstitute the marrow function of lethally irradiated mice. Such BM precursors possess the dual capacity of self-renewal as well as multilineage differentiation. This has remained the definition of stem cells to this day. The observation of these authors has also led to the idea of bone marrow transplantation in humans: If patients with leukemia were given a lethal dose of total body irradiation, which would eliminate the malignant cells as well as normal marrow precursors, an infusion of healthy BM cells would be expected to protect the patients from death.

Since then, a vast amount of knowledge has been gained through basic laboratory research and clinical trials. A gradual understanding of transplantation immunology, of human leukocyte antigen (HLA) system, of controlling opportunistic infections, and of transfusion medicine evolved in the late 1960s and early 1970s. Interest in bone marrow transplant as a treatment option for leukemia grew in the late 1970s. In the 1980s the discovery of novel cytokines as well as novel blood cell populations, and recognition of their roles in proliferation, differentiation, and regulation of hematopoietic stem cells and lineage-committed progenitors spawned another wave of interest in stem cell technology. This was accompanied in the early 1980s by advances in identification, enrichment, and amplification of hematopoietic stem and progenitor cells. Translation of such knowledge into clinical practice has been occurring at a breathtaking pace.

In the last ten years, we have witnessed an exponential growth in the numbers of transplants performed worldwide, both allogeneic and autologous, as well as in the number of transplant centers. Ten years ago, blood-derived stem cells for transplantation, CD34 separation, tumor cell purging, and progenitor cell expansion, among others, were novel ideas and their clinical applicability and relevance had yet to be proven. Some of these technologies have become clinical routine, while others have been discarded. Meanwhile, the immunological sequelae of allogeneic transplantation have been recognized as the major contributing factor for its therapeutic efficacy, whereas the long-term benefits of high-dose chemotherapy and autologous transplants for solid tumors have been questioned. The present trend is moving toward selective exploitation of the immunomodulatory effect of allogeneic stem cell transplantation. The goal is to establish chimerism and conditioning regimens that induce immunoablation only without myeloablation. Donorderived lymphocytes or subpopulations will be used for ultimate cure. Although early attempts have generated encouraging data, this strategy needs thorough evaluation in a larger number of patients and in randomized studies.

Finally, advances in molecular biology have made it feasible to correct human diseases by gene transfer. The hematopoietic system is a prime target of somatic gene therapy, because the developmental biology of hematopoiesis is well understood, HSC transplantation is a well-established procedure, and the stem cells are readily accessible.

We hope that this volume will serve as an introduction to all these fascinating aspects of hematopoietic stem cell transplantation and will be a resource for scientists and physicians alike who are searching for an overview of the scientific background, clinical advances in allogeneic and autologous transplantation, and future prospects of hematopoietic stem and progenitor cell technology.