Biology of Blood and Marrow Transplantation
Volume 13, Issue 3 , Pages 263-264, March 2007

Hematopoietic Progenitor Cell Transplantation in 2007: New Challenges and New Opportunities for the Center for International Blood and Marrow Transplant Research

  • Sergio Giralt

      Affiliations

    • Corresponding Author InformationCorrespondence and reprint requests: Sergio Giralt, MD, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.

University of Texas M.D. Anderson Cancer Center, Houston, Texas

Received 10 August 2006; accepted 15 December 2006.

Article Outline

 

This past year we celebrated the 50th anniversary of the publication of the seminal paper by Barnes and Loutit, which demonstrated for the first time in a mouse model the existence of a graft-versus-leukemia effect mediated by donor cells [1]. The paper from Barnes and Loutit represented the first seed in the development of our field. This seed bore its first fruits almost 20 years later when Dr. Thomas reported the transplant outcomes of the first 100 patients treated in Seattle with high-dose chemoradiotherapy and allogeneic transplantation as treatment of refractory leukemia [2].

The concepts of dose intensity as a strategy to overcome cancer cell resistance, hematopoietic progenitor cell rescue as a tool to deliver supralethal chemoradiotherapy, and finally the existence of an immune-mediated graft-versus-tumor effect still form the basis of our field today.

Despite the fact that we have witnessed major advances in our field, outcomes for many patients remain poor. Thus, continued research into the major causes of treatment failure such as graft-versus-host disease (GVHD), regimen-related toxicity, relapse post-transplant, and post-transplant immunedeficiency should be the main focus of our efforts. However, as I begin my term as Chairman of the Advisory Board of the Center for International Blood & Marrow Transplant Research (CIBMTR), other challenges to the future development of our field including continued research into the areas mentioned above can be identified. These areas should be addressed as opportunities to move our field forward and improve the outcomes of the patients we serve. The most pressing of these challenges as I see them are:

1.Access to Hematopoietic Progenitor Cell Transplantation: despite strong evidence demonstrating the benefits of allografting and autografting in patients with a variety of hematologic disorders, the rates of transplantation for many diseases remains low. The obvious barriers of donor availability and patient medical condition are being addressed by developing alternative donor strategies, and development of less toxic conditioning regimens. The other barriers of access to transplant specialists such as regional distribution of transplant centers, referral bias, and insurance coverage will require concerted efforts from us as transplant specialists and our professional societies to identify and address the potential root causes.

2.Displacement of Hematopoietic Progenitor Cell Transplantation by Alternative Therapies: chronic myelogenous leukemia has shown us how quickly hematopoietic progenitor cell transplantation can be replaced by alternative therapies perceived to be superior. In the case of imatinib, allograft utilization was decreasing even before the drug received U.S. Food and Drug Administration approval for frontline therapy of this disease. The results with imatinib undoubtedly justify the displacement of allografting from frontline therapy in younger patients with human leukocyte antigen (HLA)-compatible donors to second-line therapy [3]. Notwithstanding, the applicability of this algorithm to certain specific populations is not routinely addressed (ie, pediatric patients or patients with syngeneic donors), in which the risk–benefit ratio of foregoing allografting until the time of treatment failure may be totally different. With the approval of new agents for multiple myeloma, lymphoma, and myelodysplastic syndromes, many disease experts are questioning the potential role of autografting and allografting in these disorders. The role of hematopoietic progenitor transplantation will need to be reassessed with the emergence of these new agents, and we as a community should be helping to design, implement, and analyze through organizations such as the CIBMTR, the BMT Clinical Trials Network, and the ASBMT in collaboration with other cooperative groups, and disease-specific research organizations and advocacy groups such as the MMRF, the IMF, and the Leukemia and Lymphoma Society, among others.

3.Increasing Burden of Reporting and Regulatory Obligations: with the recent publication of the Health Resources and Services Administration Request for Proposals to establish and maintain the Stem Cell Therapeutic Outcomes Database it is only a matter of time before mandatory reporting of all hematopoietic progenitor cell transplants becomes the “law of the land.” Although such an initiative is appropriate, the potential for developing a large unfunded mandate may result in the closure of many small- to medium-size transplant units that will be unable to cope with the added data management demands.

4.Replacement of Trained Personnel: the care of patients undergoing hematopoietic progenitor cell transplantation has become increasingly more complex, as we transplant older patients, use alternative stem cell doses, and look into the issues of graft engineering and cellular therapies. Although FACT and the ASBMT have developed criteria for what type of training transplant specialists should have, no formal training curriculum has been developed, nor has a certification program been approved. Likewise, we need to define what the potential needs for hematopoietic progenitor transplant specialists will be so we can effectively stimulate, recruit, and train the next generation of hematopoietic progenitor cell transplantation specialists.

These challenges should actually be viewed as opportunities for the future. The number of patients undergoing autologous and allogeneic transplantation continues to increase, the potential indications promise to expand, and the possibility of improving treatment outcomes by incorporating many of the new agents being developed is tantalizing. Likewise, prospective evaluation of transplant outcome with mandatory reporting could potentially improve our abilities to demonstrate the superiority of transplant to other therapeutic strategies as well as serve as a catalyst for the eventual development of hematopoietic progenitor cell transplantation as a subspecialty with specific credentialing requirement that could serve as an incentive for physicians in training to pursue this career. I am proud to say that the CIBMTR has been, and will continue to play a major role in addressing these challenges and making them into opportunities. Some examples of how the CIBMTR is addressing these challenges include:

•Development of the Health Services Subcommittee

•Initiation of a Working Committee for International Studies.

•Partnering with the NMDP and EMMES Corporation to become the Data Coordinating Center for the BMT-CTN.

•Performing the first studies looking at center characteristics and outcomes of performance [4, 5]

•Harmonizing data reporting forms with the NMDP.

Thus, I continue to encourage all of the members of the hematopoietic progenitor cell transplantation community to actively participate in all activities concerning the CIBMTR, from data reporting to study proposals. Inasmuch as we are participants in these activities, the CIBMTR will represent our needs, and together we can improve the field of hematopoietic progenitor cell transplantation in the benefit of the patients we see and serve every day.

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References 

  1. Barnes DWH, Corp MJ, Loutit JF, Neal FE. Treatment of murine leukaemia with X-rays and homologous bone marrow (Preliminary communication). Br Med J. 1956;2:626
  2. Thomas ED, Buckner CD, Banaji M, et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977;49:511
  3. Mughal TI, Goldman JM. Chronic myeloid leukemia: current status and controversies. Oncology (Huntington). 2004;18:837–844847
  4. Loberiza FR, Zhang MJ, Lee SJ, et al. Association of transplant center and physician factors on mortality after hematopoietic stem cell transplantation in the United States. Blood. 2005;105:2979–2987
  5. Loberiza FR, Serna DS, Horowitz MM, Rizzo JD. Transplant center characteristics and clinical outcomes after hematopoietic stem cell transplantation: what do we know?. Bone Marrow Transplant. 2003;31:417–421

PII: S1083-8791(06)01308-5

doi:10.1016/j.bbmt.2006.12.444

Biology of Blood and Marrow Transplantation
Volume 13, Issue 3 , Pages 263-264, March 2007

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