T-cell depletion to prevent GVHD after unrelated-donor marrow transplantation

Despite the successes achieved by allo-HSCT, the treatment is still associated with a remarkable incidence of failures, mainly attributable to the development of immune complications (ie, graft-versus-host disease [GVHD] and graft failure),2 to relapse of malignancy,3 or to the profound state of imm...

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Bibliographic Details
Published in:The Lancet (British edition) 2005-08, Vol.366 (9487), p.692-694
Main Authors: Locatelli, Franco, De Stefano, Piero
Format: Article
Language:English
Subjects:
Bone marrow
Bone Marrow Transplantation - adverse effects
Bone Marrow Transplantation - immunology
Graft vs Host Disease - etiology
Graft vs Host Disease - prevention & control
Hematologic Diseases - therapy
Humans
Immune system
Immunology
Leukemia
Leukemia - therapy
Lymphocyte Depletion
Medical treatment
Side effects
T-Lymphocytes
Transplants & implants
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Summary:Despite the successes achieved by allo-HSCT, the treatment is still associated with a remarkable incidence of failures, mainly attributable to the development of immune complications (ie, graft-versus-host disease [GVHD] and graft failure),2 to relapse of malignancy,3 or to the profound state of immune deficiency that characterises patients given an allograft and favours the occurrence of fatal infections.4 GVHD is caused by donor-derived alloreactive T-cells contained in the graft attacking non-shared recipient antigens on target tissues. A two-step vicious circle generates the clinical syndrome: conditioning-induced tissue damage activates antigen-presenting cells (mainly of recipient origin) which present recipient alloantigens to donor T-cells transferred with the graft, and in response to recipient antigens, activated donor CD4+ cells expand and generate inflammatory cytokines that cause tissue damage and promote differentiation of cytotoxic CD8+ T-cells, which, in turn, kill recipient cells and further disrupt tissues.5 In its most severe forms, GVHD may be largely refractory to immunosuppressive therapy, leading directly or indirectly, mainly because of infections, to the patient's death. On the other hand, GVHD has been reported to be associated with a graft-versus-leukaemia (GVL) effect, because of widely distributed histocompatibility antigens of the recipient not shared by the donor. In the context of transplantation for the treatment of haematological malignancies, GVHD-assodated GVL effect results in a decreased relapse incidence.236 A more specific GVL response, not associated with the development of GVHD, and resulting from the attack towards haemopoietic-restricted or leukaemia-specific antigens, also exists and contributes to the success of allo-HSCT.3,7
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(05)66997-8