High-Dose Therapy and Transplantation of Haematopoietic Stem Cells

The field of hematopoietic stemcell transplantation is evolvingrapidly. Observations made in the laboratory can now be swiftly translated intoclinical trials. The role of hematopoietic stem cell transplantation in olderpatients, the appropriate use of transplantation in patients with advanceddiseases, and the selection of diseases amenable to this therapy continue to beredefined. Consequently, as new technologies and indications emerge, so do areasof controversy. For example, alternative donor sources such asvolunteer-unrelated, haploidentical-related, and umbilical cord blood are usedwith increasing frequency and have expanded the therapeutic options for patientswith advanced diseases.

The definition of an "appropriate candidate" fortransplantation has also changed. Moreover, recent evidence of the powerfulantitumor effects of donor leukocytes has shifted the approach to patients withdiseases responsive to immune manipulation. Reliance on high-intensity,high-toxicity conditioning regimens has been replaced by reliance onlower-intensity but more-immunosuppressive regimens. Also, the ability to modifyhematopoietic cells genetically continues to be refined in the laboratory,although the role of gene therapy targeting hematopoietic stem cells remains tobe defined in clinical trials.

In this context, High-Dose Therapy and Transplantation ofHaematopoietic Stem Cells attempts to address some of these newer developmentsthrough the publication of a series of scientific presentations made at the 4thInternational Stem Cell Workshop held in Bad Saarow (Berlin) in April 1999. Atthis workshop, an international team of experts presented their recent research.The volume covers the salient features of these presentations, which focus onthe use of hematopoietic stem cell transplantation in patients with bothmalignant and nonmalignant diseases. The book is divided into five sections:

hematologic malignancies

solid tumors 

miscellaneous issues 

experimental transplantation

novel approaches.

The section on hematologic malignancies presents a balancedoverview of current transplantation approaches in chronic lymphocytic leukemia.The authors suggest autologous transplantation may be the better option forpatients in the earlier stages of disease. However, they do not present anydiscussion on the potential negative impact of prior fludarabine (Fludara)therapy on stem cell mobilization. The reader is left with an overall impressionthat the role of allogeneic transplantation in the treatment of chroniclymphocytic leukemia remains controversial.

The group from Freiburg presented the results of allogeneictransplantation using a low-intensity conditioning regimen containingfludarabine, carmustine (BiCNU), and melphalan (Alkeran). These data arepreliminary but intriguing, and we can add this combination to the ever-growinglist of nonmyeloablative conditioning regimens. Presentations on multiplemyeloma and primary amyloidosis provide an overview of current practice, but donot offer any definitive answers about the appropriate role of hematopoieticstem cell transplantation in these diseases.

The second section, on solid tumors, is less organized than theothers. It begins with a discussion of the role of high-dose chemotherapy inmetastatic breast cancer, which is already out of date as there is no mention ofthe data misrepresentation in the trials conducted by Bezwoda. Studiesevaluating the use of large-volume apheresis for hematopoietic stem cellcollection in children and the role of high-dose therapy in sarcomas wereinformative, if not definitive. A study comparing the results of apheresisperformed on day 4 vs day 5 was provocative.

Section 3 discusses miscellaneous issues in transplantationincluding the use of high-dose therapy for systemic sclerosis, infectiouscomplications of transplantation, and the culture and storage of umbilical cordblood. These are good overviews of the current state of the art. There is also adiscussion of an interesting study performed in healthy donors of allogeneicperipheral blood stem cells that compared large-volume apheresis on day 4 tostandard-volume apheresis on day 5. The data suggest that this strategy may besuperior to the more conventional method of hematopoietic stem cell collection.Finally, there is a useful discussion by the Dusseldorf group of the variousanimal models employed in the development of antileukemia vaccines.

Section 4, on "experimental transplantation," is thehighlight of the volume. It presents a comprehensive and clear review of thecurrent state of genetic modification of hematopoietic cells forchemoprotection. The current pitfalls and areas of opportunity surroundingretroviral gene transfer into hematopoietic stem cells are presented in aconcise overview. Two excellent discussions describe first a strategy usingantisense oligonucleotides targeted to adhesion molecules, and next, themechanisms involved in the regulation of progenitor cell homing andmobilization. An interesting study conducted by the Heidelberg group suggeststhat primitive hematopoietic stem cells may maintain multipotentiality byundergoing asymmetric cell division.

The final section on novel approaches to stem celltransplantation includes a description of the Ulm group’s adoptiveimmunotherapy strategy as well as the recent Seattle experience with anonmyeloablative conditioning regimen containing low-dose total-bodyirradiation. Finally, an overview of nonmyeloablative hematopoietic stem celltransplantation is presented by the M. D. Anderson group. Each of these papersis concise and informative.

This volume will be of interest chiefly to clinical andlaboratory-based investigators working within the field of hematopoietic stemcell transplantation. The presentation of novel approaches combined withsurprisingly in-depth discussions for a volume of this size are its strengths.While there is some variability in the thoroughness of the reviews, such asthose 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-DoseTherapy and Transplantation of Haematopoietic Stem Cells will be useful toreaders who wish to gain a fuller understanding of the recent application ofnovel approaches in this continuously evolving field.