Book Review

Hematopoietic Stem Cell Therapy

N Engl J Med 2001; 344:463February 8, 2001

Article

Hematopoietic Stem Cell Therapy
Edited by Edward D. Ball, John Lister, and Ping Law. 757 pp., illustrated. Philadelphia, Churchill Livingstone, 2000. $299.50. ISBN: 0-443-07622-7

Recent developments are revolutionizing our understanding of the potential therapeutic role of what used to be called bone marrow transplantation but is now called hematopoietic stem-cell therapy. Over the past three decades, much empirical knowledge has been accumulated to provide a sound basis for the optimal use of this approach in the treatment of hematopoietic cancers, especially acute myelogenous leukemia, Hodgkin's disease and other lymphomas, and (more recently) multiple myeloma. This approach has also been used in the treatment of some solid tumors, most notably breast cancer, for which its value is still in dispute because of poor accrual in randomized trials and because it takes many years to obtain definitive answers, even from well-designed trials. Hematopoietic stem-cell therapy is also being tried in sickle cell disease and thalassemia and recently in progressive multiple sclerosis, systemic scleroderma, severe systemic lupus erythematosus, and rheumatoid arthritis with a poor prognosis.

The broadening therapeutic applications of hematopoietic stem cells also reflect an increased understanding of how to modulate the cells of the immune system to minimize both rejection and graft-versus-host disease and to improve the management of the infectious complications of immunosuppression. Tolerance and graft-versus-tumor effects are now better understood, as is the use of donor-lymphocyte infusions. This, in turn, has recently led to the concept of the “mini”-transplant; the primary goal of this approach is to make the recipient tolerant of subsequent donor-lymphocyte infusions with the use of as little cytotoxic conditioning therapy as possible. In the treatment of cancer, the effectiveness of this type of transplantation would thus be due primarily to an immunologic effect on the malignant cells rather than to a direct cytotoxic effect of high-dose chemotherapy. With this approach, it should be possible to reduce the incidence of post-transplantation cytopenia and other complications, thereby extending the potential benefits of hematopoietic stem-cell transplantation to a much larger group of older patients.

The reduction in transplantation-related morbidity and mortality will also accelerate the use of stem-cell transplantation in the treatment of inherited diseases that are not immediately life-threatening and the use of hematopoietic stem cells for gene therapy. Moreover, since adult bone marrow has recently been found to contain stem cells of previously unrecognized “plasticity” that are able to form a variety of types of cell — muscle, liver, neural, bone, cartilage, endothelial, and perhaps others — it may be possible to use marrow stem cells in cytotherapeutic approaches to a wide spectrum of diseases, such as cardiac disorders, muscular dystrophy, liver disease, neurodegenerative conditions, and joint diseases.

Hematopoietic Stem Cell Therapy is a new textbook that captures some of the excitement of these new developments, although it focuses primarily on the practical aspects of high-dose chemotherapy and hematopoietic stem-cell rescue. Its authors are knowledgeable about this approach and about the diverse and serious complications that may be encountered in its use. The roughly 700-page text is divided into three main sections covering topics relevant to the periods before, during, and after transplantation. The first section, broken down into nine chapters, covers aplastic anemia, the individual leukemias, Hodgkin's disease, other lymphomas, and multiple myeloma. It also includes chapters on solid tumors (including breast, ovarian, and germ-cell tumors and childhood cancers) and on congenital immunodeficiencies, metabolic diseases, hemoglobinopathies, Gaucher's disease, autoimmune disease, and in utero transplantation. Of interest to physicians who refer patients for transplantation are chapters on the evaluation of candidates for transplantation, the choice of donors, and the care of long-term venous access, as well as on procurement of grafts from bone marrow, peripheral blood, and umbilical-cord blood. For laboratory-based readers, there are seven chapters on stem-cell quantitation, processing and storage, purging, T-cell depletion, immunomodulation, ex vivo stem-cell expansion, and gene therapy.

The second and third sections of the book deal with the actual transplantation and its complications. Covered appropriately are conditioning regimens, infections, graft-versus-host disease, graft failure, coagulopathies, the use of growth factors, nutritional support, and liver, gastrointestinal, respiratory, and neurologic complications. Also of interest to referring physicians are chapters on late complications, including infection and immunization, endocrine and metabolic complications, myelodysplasia and second cancers, chronic graft-versus-host disease, and psychosocial issues. The book concludes with specialized chapters on nursing, data management, biostatistics, economics, and regulatory issues that will be of considerable interest to both trainees and specialists in this area.

The strength of this book lies in its practical and readable approach to hematopoietic stem-cell transplantation. All the authors are close to their subject matter, and many are well-established experts. Chapters on stem-cell biology, the history of transplantation, and the excitement and future of hematopoietic stem-cell therapy would have further embellished this otherwise highly informative textbook, which I recommend for the libraries of specialists in this technique, their trainees, and referring physicians.

Allen C. Eaves, M.D., Ph.D.
University of British Columbia, Vancouver, BC V5Z 1L3, Canada