Alternative sources of hematopoietic stem cells and their clinical applications

Abstract

Hematopoietic stem cell transplantation (HSCT) is an integral part of the comprehensive treatment of malignant as well as nonmalignant diseases of the lympho-hematopoietic system. HSCT, using autologous or allogeneic cells, has been applied as a salvage procedure to overcome the dose-limiting marrow toxicity of intensive chemotherapy. However, it was recognized early on that the use of cells from allogeneic donors, which had the undesired effect of inducing graft-versus-host disease (GVHD), was also associated with an immunotherapeutic effect against the patient’s malignancy (graft-versus-tumor [GVT] effect). In addition to human leukocyte antigen (HLA)-identical siblings, unrelated donors, umbilical cord blood, or HLA haploidentical family members serve as donors of allogeneic cells. Improved prophylactic regimens, for example, the inclusion of antithymocyte globulin or posttransplant cyclophosphamide, have reduced the incidence of GVHD while preserving the GVT effect. Recent developments are further exploiting immunotherapeutic strategies in the form of genetically modified T lymphocytes directed specifically at the patient’s malignancy.