The field of hematopoietic stem cell transplantation is evolving rapidly. Observations made in the laboratory can now be swiftly translated into clinical trials. The role of hematopoietic stem cell transplantation in older patients, the appropriate use of transplantation in patients with advanced diseases, and the selection of diseases amenable to this therapy continue to be redefined. Consequently, as new technologies and indications emerge, so do areas of controversy. For example, alternative donor sources such as volunteer-unrelated, haploidentical-related, and umbilical cord blood are used with increasing frequency and have expanded the therapeutic options for patients with advanced diseases.
The definition of an "appropriate candidate" for transplantation has also changed. Moreover, recent evidence of the powerful antitumor effects of donor leukocytes has shifted the approach to patients with diseases responsive to immune manipulation. Reliance on high-intensity, high-toxicity conditioning regimens has been replaced by reliance on lower-intensity but more-immunosuppressive regimens. Also, the ability to modify hematopoietic cells genetically continues to be refined in the laboratory, although the role of gene therapy targeting hematopoietic stem cells remains to be defined in clinical trials.
In this context, High-Dose Therapy and Transplantation of Haematopoietic Stem Cells attempts to address some of these newer developments through the publication of a series of scientific presentations made at the 4th International Stem Cell Workshop held in Bad Saarow (Berlin) in April 1999. At this workshop, an international team of experts presented their recent research. The volume covers the salient features of these presentations, which focus on the use of hematopoietic stem cell transplantation in patients with both malignant and nonmalignant diseases. The book is divided into five sections:
The section on hematologic malignancies presents a balanced overview of current transplantation approaches in chronic lymphocytic leukemia. The authors suggest autologous transplantation may be the better option for patients in the earlier stages of disease. However, they do not present any discussion on the potential negative impact of prior fludarabine (Fludara) therapy on stem cell mobilization. The reader is left with an overall impression that the role of allogeneic transplantation in the treatment of chronic lymphocytic leukemia remains controversial.
The group from Freiburg presented the results of allogeneic transplantation using a low-intensity conditioning regimen containing fludarabine, carmustine(Drug information on carmustine) (BiCNU), and melphalan(Drug information on melphalan) (Alkeran). These data are preliminary but intriguing, and we can add this combination to the ever-growing list of nonmyeloablative conditioning regimens. Presentations on multiple myeloma and primary amyloidosis provide an overview of current practice, but do not offer any definitive answers about the appropriate role of hematopoietic stem cell transplantation in these diseases.
The second section, on solid tumors, is less organized than the others. It begins with a discussion of the role of high-dose chemotherapy in metastatic breast cancer, which is already out of date as there is no mention of the data misrepresentation in the trials conducted by Bezwoda. Studies evaluating the use of large-volume apheresis for hematopoietic stem cell collection in children and the role of high-dose therapy in sarcomas were informative, if not definitive. A study comparing the results of apheresis performed on day 4 vs day 5 was provocative.
Section 3 discusses miscellaneous issues in transplantation including the use of high-dose therapy for systemic sclerosis, infectious complications of transplantation, and the culture and storage of umbilical cord blood. These are good overviews of the current state of the art. There is also a discussion of an interesting study performed in healthy donors of allogeneic peripheral blood stem cells that compared large-volume apheresis on day 4 to standard-volume apheresis on day 5. The data suggest that this strategy may be superior to the more conventional method of hematopoietic stem cell collection. Finally, there is a useful discussion by the Dusseldorf group of the various animal models employed in the development of antileukemia vaccines.
Section 4, on "experimental transplantation," is the highlight of the volume. It presents a comprehensive and clear review of the current state of genetic modification of hematopoietic cells for chemoprotection. The current pitfalls and areas of opportunity surrounding retroviral gene transfer into hematopoietic stem cells are presented in a concise overview. Two excellent discussions describe first a strategy using antisense oligonucleotides targeted to adhesion molecules, and next, the mechanisms involved in the regulation of progenitor cell homing and mobilization. An interesting study conducted by the Heidelberg group suggests that primitive hematopoietic stem cells may maintain multipotentiality by undergoing asymmetric cell division.
The final section on novel approaches to stem cell transplantation includes a description of the Ulm group’s adoptive immunotherapy strategy as well as the recent Seattle experience with a nonmyeloablative conditioning regimen containing low-dose total-body irradiation. Finally, an overview of nonmyeloablative hematopoietic stem cell transplantation is presented by the M. D. Anderson group. Each of these papers is concise and informative.
This volume will be of interest chiefly to clinical and laboratory-based investigators working within the field of hematopoietic stem cell transplantation. The presentation of novel approaches combined with surprisingly in-depth discussions for a volume of this size are its strengths. While there is some variability in the thoroughness of the reviews, such as those covering breast cancer, the overall impression is positive.
In summary, although it is not intended to be a comprehensive "a to z" review of hematopoietic stem cell transplantation, High-Dose Therapy and Transplantation of Haematopoietic Stem Cells will be useful to readers who wish to gain a fuller understanding of the recent application of novel approaches in this continuously evolving field.