Bone marrow transplantation: new approaches to immunosuppression and management of acute graft-versus-host disease.
OBJECTIVE
Acute graft-versus-host disease (GVHD) significantly limits the application and the success of allogeneic hematopoietic stem cell transplantation (HSCT). Novel therapies that target the aberrant immune response underlying GVHD are reviewed with particular emphasis on immunomodulatory agents currently incorporated into clinical trials. In addition, regenerative stromal cellular therapy (RSCT) is discussed as an emerging form of novel GVHD therapy.


RESULTS
Knowledge for transplant immunology, particularly as it relates to underlying pathophysiology of GVHD, has dramatically increased over the last decade. As a result, new immunomodulatory therapies have been used to treat steroid-refractory GVHD. However, their success has been limited by their lack of clinical experience during HSCT as well as by their associated toxicity profiles. RSCT uniquely offers the potential to enhance donor-derived hematopoiesis and immunity and to ameliorate adverse sequelae associated with GVHD.


CONCLUSIONS
An exciting era incorporating the use of cellular therapeutics during HSCT has arrived. As the experience and understanding for cellular therapies, in general, and RSCT, in particular, increases, so too will their success in benefiting the HSCT recipient beyond limitations of current pharmaceutical agents.
Auletta
Jeffery J
JJ
Pediatric Hematology/Oncology and Infectious Diseases, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
Cooke
Kenneth R
KR
D000208:Acute Disease; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000379:methods*; D002986:Clinical Trials as Topic; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D010372:Pediatrics / Q000379:methods; D012720:Severity of Illness Index; D017154:Stromal Cells / Q000637:transplantation; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome
D007166:Immunosuppressive Agents