Low-intensity allogeneic hematopoietic stem cell transplantation for myeloid malignancies: separating graft-versus-leukemia effects from graft-versus-host disease

Abstract

Purpose of review: Over the past several years, significant advances in allogeneic hematopoietic cell transplantation (HCT), specifically the development of nonablative and reduced-intensity conditioning regimens, have enabled the extension of transplantation to include older or medically infirm patients with myeloid malignancies. The regimens rely largely on graft-versus-leukemia effects rather than high-dose therapy to eliminate malignant cells. Studies have demonstrated that the regimens allow sustained engraftment with relatively low transplant-related mortality. However, conclusions regarding the ultimate efficacy of these regimens for myeloid malignancies have been limited, given the small numbers of patients who have had transplants so far. This review summarizes recent studies of nonablative or reduced-intensity regimens for patients with myeloid malignancies (acute and chronic myelogenous leukemia, myelodysplastic syndrome, and myeloproliferative disorders). In addition, this review evaluates what is currently known regarding the association of graft-versus-leukemia responses and graft-versus-host disease (GVHD). When possible, graft-versus-leukemia responses are highlighted in the articles discussed.

Recent findings: This review covers six articles and four abstracts that have been published since September 2003 on patients with myeloid malignancies who received HCT following nonmyeloablative or reduced-intensity conditioning. Due to the heterogeneity of the conditioning and GVHD prophylaxis regimens, direct comparisons between studies are difficult. However, these studies have demonstrated encouraging overall survivals (30 to 74%), disease-free/event-free or progression-free survivals (19 to 62%), and nonrelapse mortalities (15 to 55%). In addition, these studies demonstrated evidence for graft-versus-leukemia responses. However, relapse and progressive disease continued to be problems, particularly in patients with large tumor burdens at time of HCT.

Summary: Over the past 10 years, significant advances have been made in the field of transplantation. Nonmyeloablative and reduced-intensity HCT have promised patients with hematologic and nonhematologic malignancies potential cures. However, disease relapse and nonrelapse mortality, mainly from GVHD and its therapy, continue to be problems. Future studies are needed to increase our understanding of GVHD and graft-versus-leukemia responses, which will greatly improve outcome. In addition, a better understanding of minor histocompatibility antigens may lead to more targeted immunotherapy and enhance the precision and success of transplantation.