Improving immune reconstitution while preventing GvHD in allogeneic stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematologic malignancies and inherited disorders of the hematopoietic system. Ex vivo T-cell depletion (TCD) of the graft and post-transplantation immunosuppression efficiently prevents the development of GvHD in no- MHC-identical settings. However, the consequence of these non-specific strategies is a long-lasting immunodeficiency associated with increased incidence of disease relapse, graft rejection and reactivation of viral infections. Donor lymphocyte infusion, which is used for treating leukemic relapse after allogeneic HSCT, can result in severe GvHD. Several strategies are being optimized specifically to inactivate anti-host T cells while preserving anti-leukemic or anti-microbial immunocompetence. Based on the ex vivo or in vivo elimination of anti-host T cells, or on the modulation of their anti-host activity, these approaches, which have been explored extensively in pre-clinical studies and tested in some preliminary clinical trials, are discussed in this paper.
André-Schmutz
I
I
INSERM U429 and Biotherapy Department, Division of Pediatric Immunology and Haematology, Necker Hospital for Sick Children, 149 rue de Sevres, 75743 Paris Cedex 15, France.
Dal Cortivo
L
L
Fischer
A
A
Cavazzana-Calvo
M
M
D002986:Clinical Trials as Topic; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D008212:Lymphocyte Depletion / Q000379:methods*; D017710:Lymphocyte Transfusion / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous