The role of non-myeloablative conditioning in allowing engraftment of allogeneic hematopoietic cells for correction of genetic disorders and for immunotherapy of leukemia.
Transplant lite or allogeneic bone marrow transplantation after non-myeloablative conditioning is a novel approach to the treatment of hematological malignancies and genetic diseases, which hinges on the replacement of myeloablative conditioning regimen prior to transplant (i.e., destruction of the entire hematopoietic system of the recipient) by immune ablation (i.e. destruction of only immune system rejecting the transplant). Infused hematopoietic cells have to engraft in the presence of host hematopoietic cells that survive conditioning. The net result is the appearance of the so called mixed chimerism, which indicates the presence of a variable number of donor cells among cells of host origin. Further immunomodulation after transplantation is used to increase engraftment, decrease graft versus host disease and to maintain graft versus disease effect. This strategy permits allogeneic transplantation to be used in older patients and those with comorbidities that are unable to tolerate conventional high-dose preparative regimens. In consequence, it would increase the range of disorders to be treated with bone marrow transplantation. Additionally, this could be supplemented by the transfer of immune cells of bone marrow transplant donor to induce graft-versus leukemia effect. Different non-myeloablative conditioning regimens have been proposed: one regimen is using low dose TBI [200 cGy] and several others are based on purine analogues. The aim of this review is to describe this new allogeneic approach to the treatment of hematological malignancies as well as genetic disorders.
Awedan
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Department of Hematology, Oncology, and Internal Medicine, Medical University of Warsaw, Poland.
D016026:Bone Marrow Transplantation / Q000379:methods / Q000502:physiology*; D030342:Genetic Diseases, Inborn / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007938:Leukemia / Q000628:therapy*; D019653:Myeloablative Agonists / Q000627:therapeutic use; D014184:Transplantation, Homologous
D019653:Myeloablative Agonists