Allogeneic hematopoietic
cell transplantation (HCT) is an increasingly widely used treatment modality in
hematological malignancies. Alloreactivity mediated by donor T cells (and, in some settings, by donor natural killer cells) can produce durable immunologic control or eradication of residual
malignancy after allogeneic HCT. However, graft-vs.-
tumor (GVT) effects are variably effective and are often accompanied by deleterious alloreactivity against normal host tissue, manifesting as
graft-vs.-host disease (GVHD). A major focus of current research in HCT is the separation of beneficial GVT effects from GVHD. Here we review a number of approaches currently under investigation to specifically augment GVT effects, including the identification of
minor histocompatibility antigens (mHA), adoptive immunotherapy with
tumor-specific or mHA-specific cytotoxic T lymphocytes, vaccination of the donor or recipient to stimulate
tumor-specific immunity, and adoptive transfer of natural killer cells. In addition, we review strategies being investigated to specifically suppress GVHD while sparing GVT, including the manipulation and infusion of regulatory T cells, the use of novel pharmacologic and
biologic agents, and the use of mesenchymal stem cells. Ultimately, advances in separation of GVT from GVHD will further enhance the potential of allogeneic HCT as a curative treatment for
hematological malignancies.