Non-myeloblative induction of mixed hematopoietic chimerism: application to transplantation tolerance and hematologic malignancies in experimental and clinical studies.

Abstract

This cyclophosphamide-based non-myeloablative preparative regimen for HLA-matched or -mismatched allogeneic bone marrow transplantation is generally well-tolerated and has been associated with striking anti-tumor responses in some recipients with chemorefractory hematologic malignancies. GVHD has occurred in a minority of recipients of HLA-matched donor transplants (prior to prophylactic DLI); the high incidence of GVHD following HLA- mismatched donor transplants in which ATG was utilized suggest inadequate in vivo T cell depletion in these cases. Graft rejection in the HLA-matched donor transplant setting, which has occurred in a significant percentage of patients, may be associated with a suboptimal anti-tumor response. Sustained anti-tumor responses with minimal GVHD have been seen in some recipients of prophylactic DLI. However, GVHD, when it has occurred, has sometimes been severe. It may be important to revise the schedule and perhaps dosing of DLI according to patterns of chimerism (increasing or decreasing) and the underlying disease (indolent versus aggressive).KeywordsMixed ChimerismTransplantation ToleranceTotal Lymphoid IrradiationCostimulatory BlockadeDonor Lymphocyte InfusionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.