Emerging therapies for graft-versus-host disease.
Acute graft-versus-host disease (GVHD) and chronic GVHD remain the major barriers to successful haematopoietic cell transplantation. The induction of GVHD may be divided into three phases: (i) recipient conditioning, (ii) donor T cell activation, and (iii) effector cells mediating GVHD. Standard agents and agents under development to prevent and treat GVHD are discussed. The various pharmacological agents impact on different phases of the GVHD cascade. Sirolimus is a new immunophilin binding agent that appears to be synergistic with tacrolimus and cyclosporin. It also seems to promote allograft tolerance. Mycophenolate mofetil (MMF) is an antimetabolite that is currently under study for prophylaxis and treatment of acute and chronic GVHD; results are encouraging. Other agents such as the purine analogue pentostatin and the monoclonal antibodies alemtuzumab, daclizumab and infliximab are discussed at length within the GVHD context. The most effective approach to GVHD prevention will likely be a combination regimen where the three phases of the GVHD cascade are disrupted. Once GVHD has occurred, all three phases of the cascade are activated. Developments of combination therapy for the treatment of both acute and chronic GVHD will likely yield better results than monotherapy. The numerous new treatment modalities presented should improve the outlook for acute and chronic GVHD.
Jacobsohn
David A
DA
Department of Pediatrics, Northwestern University, The Feinberg School of Medicine, Children's Memorial Hospital, 2300 Children's Plaza, Box 30, Chicago, IL 60614, USA. djacobsohn@childrensmemorial.org
D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents