Allogeneic hematopoietic cell transplantation: the state of the art

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative procedure for a variety of hematologic malignancies. The field has evolved substantially over the past decade, with advances in patient and donor selection, stem cell sources, supportive care, prevention of complications and reduced-toxicity preparative regimens. As a result, the indications for HCT and the pool of eligible patients have expanded significantly. In this article, we provide an overview of the major aspects of allogeneic HCT, and focus specifically on areas of active research and on novel approaches to challenges in the field. Specifically, we will discuss approaches to reduce the toxicity of the preparative regimen, with the goal of increasing the safety and applicability of HCT. The availability of suitable donors may be an obstacle to wider application of HCT. We review three major approaches to broadening the donor pool: the use of HLA-mismatched unrelated donors, umbilical cord blood and HLA-haploidentical family donors. Graft-versus-host disease remains a major cause of morbidity and mortality after HCT. We review recent advances in the understanding of this phenomenon, and novel prophylactic and therapeutic approaches that hold the promise of further improving the safety of the procedure. We conclude with a speculative outline of the next 5 years of research in the field of HCT.

Keywords: bone marrow transplantation; graft-versus-host disease; hematopoietic cell transplantation.

Figure 1. Indications for allogeneic hematopoietic cell transplantation in North America 2005

Data from the Center for International Blood and Marrow Transplant Research (CIBMTR). AML: Acute myeloid leukemia; ALL: Acute lymphoblastic leukemia; CML: Chronic myelogenous leukemia; MDS: Myelodysplastic syndrome; MPD: Myeloproliferative disorders; NHL: Non-Hodgkin lymphoma. Reprinted with permission from CIBMTR (2009).

Figure 2. Trends in allogeneic transplantation by recipient age (1987–2006)

Data from from the Center for International Blood and Marrow Transplant Research (CIBMTR). Reprinted with permission from CIBMTR (2009).

Figure 3. Data from the US National Marrow Donor Program (NMDP)

Reprinted with permission from [201].

Figure 4. Nonmyeloablative conditioning regimen for hematopoietic cell transplantation developed at Fred Hutchinson Cancer Research Center (WA, USA)

CSP: Cyclosporine; MMF: Mycophenolate mofetil; TBI: Total-body irradiation.

Figure 5. Spectrum of intensity of commonly used conditioning regimens for hematopoietic cell transplantation

ATG: Antithymocyte globulin; BU: Busulfan; CY: Cyclophosphamide; FLU: Fludarabine; MP: Melphalan; TBI: Total-body irradiation; TT: Thiotepa. Reproduced from [132].