Mini-allografts: ongoing trials in humans

Conventional allogeneic stem cell transplantation is a valuable approach to therapy for many hematcologic malignancies. However, high-dose conditionin g regimens designed both to control the malignancy and to prevent graft rej ection are associated with a high incidence of acute and long-term side-eff ects. This has largely precluded the use of allografting for patients elder than 55 years or for younger patients with certain preexisting organ damag e. In order to manage the side-effects, transplants have traditionally been delivered in highly specialized hospital wards or intensive care settings. Thus, an important goal is to develop safer allografting procedures that c an be extended to older patients or patients with pre-existing organ dysfun ction who are currently excluded from consideration for transplant, Recent observations have shown that donor lymphocyte infusions (DLI) can eradicate some malignancies that relapse after conventional allografting. These obse rvations confirmed earlier evidence in favor of a graft-versus-leukemia eff ect based on the association of graft-versus-host disease (GVHD) with a low er likelihood of relapse of malignancy after allografting, Given the potent ial efficacy of DLI as the sole modality for eradication of malignancy, new strategies for allografting can incorporate the concept of less intensive conditioning therapy which is given with the sole aim of facilitating allog eneic engraftment, Recent pre-clinical studies in a canine model have shown that conditioning regimens for allografting can be markedly reduced in int ensity yet still achieve the goal of engraftment, This review briefly summa rizes the initial translational clinical studies, using a minimally myelosu ppressive-conditioning regimen based on low dose total body irradiation (TB I) or fludarabine alone or in combination with other drugs followed by a sh ort course of immunosuppression with post-grafting cyclosporine and methotr exate or mycophenolate mofetil.