High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation.
Graft-versus-host disease, or GVHD, is a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of hematologic malignancies. Here, we describe a novel method for preventing GVHD after alloHSCT using high-dose, post-transplantation cyclophosphamide (Cy). Post-transplantation Cy promotes tolerance in alloreactive host and donor T cells, leading to suppression of both graft rejection and GVHD after alloHSCT. High-dose, post-transplantation Cy facilitates partially HLA-mismatched HSCT without severe GVHD and is effective as sole prophylaxis of GVHD after HLA-matched alloHSCT. By reducing the morbidity and mortality of alloHSCT, post-transplantation Cy may expand the applications of this therapy to the treatment of autoimmune diseases and non-malignant hematologic disorders such as sickle cell disease.
Luznik
Leo
L
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 288 Bunting-Blaustein Cancer Research Building, Baltimore, MD 21231, USA.
Fuchs
Ephraim J
EJ
D000818:Animals; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D023001:Transplantation Tolerance / Q000187:drug effects* / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide