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high-toxicity conditioning regimens has been replaced by reliance on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 (BiCNU), and 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.