BOOK REVIEW

Current Controversies in Bone Marrow Transplantation

Brian J. Bolwell, ed. Totowa (NJ): Humana Press, 1999. 336 pp., illus., $125. ISBN 0-89603-782-7

Görgün Akpek

Correspondence to: Görgün Akpek, M.D., Division of Hematologic Malignancies, The Johns Hopkins Oncology Center, Bunting and Blaustein Cancer Research Bldg., 1650 Orleans St., Floor 2M, Baltimore, MD 21231 (e-mail: gakpek{at}jhmi.edu).

Hematopoietic stem cell transplantation is a constantly evolving therapy for many hematologic malignancies, as well as for selected solid tumors. Current Controversies in Bone Marrow Transplantation, edited by Brian J. Bolwell of the Cleveland Clinic, provides useful insights about the most common clinical questions that are still being debated by physicians who work in the field of hematopoietic stem cell transplantation. The topics range from transplant strategies to the complications of bone marrow transplantation (BMT) and include a discussion of the indications, benefits, and the risk of this treatment for a variety of leukemias, lymphomas, and solid tumors.

Unlike textbooks, this book is a personal, expert commentary on and interpretation of the data reported in the recent literature. No book or review is capable of eliminating the controversies in the field of BMT, particularly in the era of rapidly developing alternative ways of transplant and treatments of neoplastic disorders; experts in the field hold many differing opinions about transplant strategies and transplant outcomes.

The first chapter by L. C. O’Donnell et al. discusses how many cells are sufficient for engraftment of various types of hematopoietic stem cell transplants. It is a well-written, useful summary. The second chapter by B. J. Bolwell discusses whether or not older patients should undergo transplant therapy. Unfortunately, much of the available literature concerning the outcome of older patients undergoing transplant therapy is not current. Furthermore, the role of allogeneic transplant in the elderly population is not addressed well, since there are very limited data in the literature that evaluate the overall impact of various type of transplants, particularly allogeneic bone marrow transplant in elderly patients. Nonetheless, B. J. Bolwell attempts to make the point that the decision to perform a BMT should be more a question of physiologic age than of chronologic age. Obviously, this issue, particularly in the context of allogeneic BMT, will remain unanswered until more convincing data are available.

The role of umbilical cord blood (UCB) transplantation in both children and adults is discussed in the third chapter. M. J. Laughlin discusses various aspects of UCB transplantation, including problems in hematopoietic recovery, associated graft-versus-host disease (GVHD), and the potential of graft-versus-leukemia and immunologic recovery following UCB transplant. The effect of human leukocyte antigen (HLA) disparity on the UCB transplant outcome was unclear when the author wrote this chapter; however, there is growing evidence that HLA disparity of up to three antigen mismatches does not seem to influence UCB transplant outcome. The ongoing clinical investigations on UCB transplantation have focused on increasing the CD34+ cell dose either by ex vivo expansion or by mixture of two HLA-identical cord blood grafts for one recipient. It would have been interesting to have seen a discussion of the disease types that are relatively not indicated for consideration for UCB transplant, particularly in adults. For example, chronic myelogenous leukemia is currently not considered for UCB transplant because of its relatively long course and the availability of other treatment modalities that are associated with less morbidity/mortality and prolonged survival.

In the fourth chapter, E. A. Copelan compares busulfan/cyclophosphamide and cyclophosphamide/total-body irradiation (TBI) as preparative regimens for allogeneic stem cell transplantation. The discussion of the pros and cons of each regimens and the expert commentary on how to select the optimum regimen on the basis of the type of the disease being treated, center experience, financial factors, and type of transplant are excellent.

In the next chapter, S. R. Wiersma and S. B. Shurin discuss the value of a TBI-based regimen in transplantation of pediatric acute lymphoblastic leukemia (ALL). They present recent data showing that a TBI-based regimen seems to be superior to a busulfan-based regimen in this pediatric population in terms of transplant-related mortality, leukemia-free survival, and overall survival. On the basis of this report, the authors strongly favor the TBI-conditioning regimen in the pediatric ALL group. However, it should be noted that this was not a prospective, randomized study and potential late effects of TBI-based regimens in pediatric population should not be underestimated.

Chapter 6, on stem cell transplantation for chronic myelogenous leukemia (CML), mostly consists of a summary of the literature. The point made by the author about unrelated BMT versus interferon as an initial therapy for CML patients who have no HLA-matched siblings is subject to controversy. The more recent data that were probably not available at the time the chapter was written suggests that pretransplant interferon treatment has no effect on transplant outcome if it is discontinued within 3 months before transplant. T-cell depleted (TCD) transplant in CML is another controversial issue among transplant physicians. In view of the use of scheduled donor leukocyte infusions, which may counterbalance the increased relapse rate associated with TCD transplant, this procedure will continue to be used by transplant centers. This chapter would have been more satisfactory if the discussion about these issues had been more extensive.

In chapter 7, the authors recommend allogeneic BMT in all adult patients with ALL with the only exception of those who have an exceedingly low risk of relapse. I concur, given that ALL remains the worst type of leukemia in adults, with 20%–25% leukemia-free survival with conventional treatments. The very high risk of relapse justifies the use of allogeneic BMT in most patients.

Chapter 8 discusses the outcome of treatment of refractory acute leukemia with BMT. Details on the realistic clinical outcome of allogeneic BMT for those patients with refractory disease are given. The author states that only 20% and 10% matched-sibling and matched unrelated allogeneic BMT in this group of patients, respectively, demonstrated long-term leukemia-free survival. The transplant decision in this poor-risk group is discussed from the perspectives of both community oncologists and transplant clinicians.

In chapter 9, the authors have nicely summarized the most recent literature in autologous stem cell transplantation in leukemias. As they indicate, a number of randomized trials in acute myelogenous leukemia have failed to demonstrate a clear benefit to autotransplant in first remission. Also, no convincing evidence exists that shows a survival benefit with autologous BMT in other types of leukemias, such as acute lymphoblastic leukemia in first remission, CML, and chronic lymphocytic leukemia. Therefore, the authors emphasize the need for developing potential strategies that may improve the results with autologous transplant in the future.

The next chapter discusses the indications for autologous transplant in patients with Hodgkin’s lymphoma, the potential benefit of post-transplant radiation therapy, prognostic factors affecting the transplant outcome, and the role of upfront transplant and double transplant in patients with Hodgkin’s disease. Overall, this chapter is a nice review of the current standard approaches in transplantation to treat Hodgkin’s disease.

Hematopoietic stem cell transplantation for mantle cell lymphoma is a real controversy as opposed to some other topics included in this book. Chapter 11 deals with the issues affecting transplant outcome in this clinically aggressive, chemotherapy-resistant lymphoma subtype. Unfortunately, this chapter does not include the new immunobiologic treatment approaches, such as anti-CD20 monoclonal antibody therapy, which could potentially improve the autotransplant outcome when combined with other approaches during the stem cell collection and/or post-transplant period.

Chapter 12 analyzes the efficacy of autologus transplantation for patients with non-Hodgkin’s lymphoma, both for those who have had a relapse and for those who are at risk at diagnosis, as well as for patients with follicular lymphomas. The author emphasizes that a minority of appropriate transplant candidates are currently being referred to transplant centers. However, the comments on the role of straightforward autologous transplant in patients with follicular lymphoma are too personal and may mislead some readers. As stated by the author, autologous transplant in lymphomas might be underutilized in some areas depending on various factors. However, it is mandatory for us to state that it should also not be overutilized in certain group of patients with lymphoma, outside the context of clinical trials that evaluate novel therapeutic approaches combined with autologous transplant.

In the third part of the book, transplantation for solid tumors is discussed. So far, autologous transplant has failed to improve survival outcome in many solid tumors, with just a few exceptions. The argument that such transplants improve the quality of life and prolong disease-free survival will probably keep the discussion on autologous transplant in solid tumor going for a while. The first three chapters of this section of the book provide a critical analysis of the indications for autologous transplant in ovarian and breast cancers. The best management approaches in inflammatory breast cancer, including the role of autologous transplantation in this condition, are appropriately discussed in a separate chapter. Promising data support the administration of autologous BMT for the treatment of inflammatory breast cancers, and the authors nicely summarize these studies, emphasizing the importance of a multidisciplinary approach for the treatment of this rare, aggressive form of breast cancer.

Transplant-related complications are discussed in the final part of the book. The lack of progress in the management of acute GVHD is emphasized, but there are few comments on chronic GVHD. The content of this chapter does not seem to fit the aim of this book. It gives the impression that it was written for purposes other than for discussing the controversies in GVHD, such as diagnosis and treatment of steroid-refractory GVHD. Despite the fact that chronic GVHD has been increasingly recognized as a late transplant complication, unfortunately chronic GVHD has not been included in the scope of this book.

Veno-occlusive disease is discussed by S. I. Bearman, who has worked extensively in prophylaxis and management of this early transplant-related complication. While many therapeutic interventions have been attempted, few have shown clear-cut efficacy as discussed in this brief summary.

Post-transplant myelodysplasia and acute leukemia are reviewed in depth in chapter 19. This well-written chapter emphasizes the difficulties in the management of these secondary or therapy-related myelodysplasias and leukemias and the influential effect of high-dose chemotherapy and autologous transplant in inducing these late complications, particularly in patients with Hodgkin’s disease and non-Hodgkin’s lymphoma.

The book closes with two chapters that discuss the challenges in the prevention and management of two common and potentially life-threatening infectious complications of allogeneic BMT, aspergillosis and cytomegalovirus infections.

In conclusion, this book is useful, with a few limitations, for every physician involved in the management of patients with transplant approach. Although it lacks some of the new data, which is unavoidable for all books, it does contain updated material for the most part. The major weakness of the book is that it has not included the exciting developments and controversies in the areas of cell therapy and nonmyeloablative transplant. Other than that, this book is successful in general and represents the most useful snapshots of many current issues in the field of transplantation.



             
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