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The chemokine system. in allogeneic stem-cell transplantation: a possible therapeutic target?

Journal

EXPERT REVIEW OF HEMATOLOGY
Volume 4, Issue 5, Pages 563-576

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1586/EHM.11.54

Keywords

acute myeloid leukemia; allogeneic stem-cell transplantation; graft-versus-host disease; graft-versus-leukemia effect; GVHD; GVL effect; peripheral blood stem-cell mobilization; T cells

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Funding

  1. Norwegian Cancer Society

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Further improvements in allogeneic stem-cell transplantation will probably depend on a better balance between immunosuppression to control graft-versus-host disease and immunological reconstitution sufficient to ensure engraftment, reduction of infection-related mortality and maintenance of post-transplant antileukemic immune reactivity. The chemokine network is an important part of the immune system, and, in addition, CXCL12/CXCR4 seem to be essential for granulocyte colony-stimulating factor-induced stem-cell mobilization. Partial ex vivo graft T-cell depletion based on the expression of specific chemokine receptors involved in T-cell recruitment to graft-versus-host disease target organs may also become a future therapeutic strategy; an alternative approach could be pharmacological inhibition (single-receptor inhibitors or dual-receptor inhibitors) in vivo of specific chemokine receptors involved in this T-cell recruitment. Future clinical studies should therefore be based on a better characterization of various immunocompetent cells, including their chemokine receptor profile, both in the allografts and during post-transplant reconstitution.

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