PuSH - Publication Server of Helmholtz Zentrum München

Kolb, H.-J. ; Schmid, C. ; Barrett, A.J.* ; Schendel, D.J.

Graft-versus-leukemia reactions in allogeneic chimeras.

Blood 103, 767-776 (2003)
Publ. Version/Full Text DOI
Closed
Open Access Green as soon as Postprint is submitted to ZB.
There is a strong graft-versus-leukemia (GVL) effect of allogeneic stem cell trans- plantation (SCT) due to elimination of tumor cells by alloimmune effector lym- phocytes. When leukemia relapses after allogeneic SCT, donor lymphocyte trans- fusions (DLTs) can induce sustained re- missions in some patients. This review summarizes the current status on clinical use of DLT, the basis of GVL reactions, problems associated with this therapy, and new strategies to improve DLT. Sev- eral multicenter surveys demonstrated that the GVL effect of DLT is most effec- tive in chronic myelogenous leukemia (CML), whereas it is less pronounced in acute leukemia and myeloma. Cytokine stimulation to induce differentiation of myeloid progenitor cells or to up-regulate costimulatory molecules on tumor cells may improve the efficacy of DLT. Infec- tions and graft-versus-host disease (GVHD) are major complications of DLT. Control of GVHD may be improved using suicide gene–modified T cells for DLT, allowing T-cell elimination if severe GVHD develops. Hopefully, in the future, GVL effect can be separated from GVHD through adoptive transfer of selected T cells that recognize leukemia-specific an- tigens or minor histocompatibility anti- gens, which are expressed predominantly on hematopoietic cells, thereby preclud- ing attack of normal tissues. In patients with leukemia and lymphomas with fast progression, tumor growth may outpace development of effector T cells. Here it may be preferable to select stem cell transplant donors with HLA-mismatches that allow alloreactive natural killer cells, which appear early after transplantation, to retain their cytolytic function. New ap- proaches for adoptive immune therapy of leukemia, which promise a better progno- sis for these patients, are being devel- oped.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
9.631
0.000
270
352
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Bone-Marrow-Transplantation; Stem-Cell Transplantation; Chronic Myeloid-Leukemia; Chronic Myelogenous Leukemia; Donor Leukocyte Infusions; Cytotoxic T-Lymphocytes; Minor Histocompatibility Antigens; Kir Ligand Incompatibility; Relapsed Multiple-Myeloma; Host-Disease
Language english
Publication Year 2003
HGF-reported in Year 0
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Journal Blood
Quellenangaben Volume: 103, Issue: 3, Pages: 767-776 Article Number: , Supplement: ,
Publisher American Society of Hematology
Reviewing status Peer reviewed
Institute(s) CCG Hematopoetic Cell Transplants (IMI-KHZ)
Institute of Molecular Immunology (IMI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-520300-001
G-501700-001
Erfassungsdatum 2003-12-31