Lymphocyte depletion in bone marrow transplantation: Will modulation of graft-versus-host disease prove to be superior to prevention?

Despite its detrimental effects, graft-versus-host disease (GVHD) has antileukemic properties as evidenced by a lower relapse rate in patients who develop GVHD following allogenic bone marrow transplantation. Meaningful long-term survival may be achieved if this latter property can be retained at the same time that the deleterious immune sequelae of acute and chronic GVHD are diminished. This is the focus of several recent graft engineering protocols. Various bone marrow components (lymphocytes, hematopoietic stem cells, and committed progenitor cells) can now be isolated and then used to reformulate the marrow graft. Combined with host immunosuppression or cytokine augmentation, it now may be possible to modulate GVHD such that its beneficial properties are enhanced without incurring its life-threatening side effects.