TY - JOUR
T1 - NCI First International Workshop on The Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation
T2 - Report from the Committee on the Biology Underlying Recurrence of Malignant Disease following Allogeneic HSCT: Graft-versus-Tumor/Leukemia Reaction
AU - Miller, Jeffrey S.
AU - Warren, Edus H.
AU - van den Brink, Marcel R.M.
AU - Ritz, Jerome
AU - Shlomchik, Warren D.
AU - Murphy, William J.
AU - Barrett, A. John
AU - Kolb, Hans Jochem
AU - Giralt, Sergio
AU - Bishop, Michael R.
AU - Blazar, Bruce R.
AU - Falkenburg, J. H.Frederik
PY - 2010/5
Y1 - 2010/5
N2 - The success of allogeneic hematopoietic stem cell transplantation (HSCT) depends on the infusion of benign stem cells as well as lymphocytes capable of participating in a graft-versus-tumor/leukemia (GVL) reaction. Clinical proof of concept is derived from studies showing increased relapse after the infusion of lymphocyte depleted hematopoietic grafts as well as the therapeutic efficacy of donor lymphocyte infusions without chemotherapy to treat relapse in some diseases. Despite this knowledge, relapse after allogeneic HSCT is common with rates approaching 40% in those with high-risk disease. In this review, we cover the basic biology and potential application to exploit adaptive T cell responses, minor histocompatibility antigens, contraction and suppression mechanisms that hinder immune responses, adaptive B cell responses and innate NK cell responses, all orchestrated in a GVL reaction. Optimal strategies to precisely balance immune responses to favor GVL without harmful graft-versus-host disease (GVHD) are needed to protect against relapse, treat persistent disease and improve disease-free survival after HSCT.
AB - The success of allogeneic hematopoietic stem cell transplantation (HSCT) depends on the infusion of benign stem cells as well as lymphocytes capable of participating in a graft-versus-tumor/leukemia (GVL) reaction. Clinical proof of concept is derived from studies showing increased relapse after the infusion of lymphocyte depleted hematopoietic grafts as well as the therapeutic efficacy of donor lymphocyte infusions without chemotherapy to treat relapse in some diseases. Despite this knowledge, relapse after allogeneic HSCT is common with rates approaching 40% in those with high-risk disease. In this review, we cover the basic biology and potential application to exploit adaptive T cell responses, minor histocompatibility antigens, contraction and suppression mechanisms that hinder immune responses, adaptive B cell responses and innate NK cell responses, all orchestrated in a GVL reaction. Optimal strategies to precisely balance immune responses to favor GVL without harmful graft-versus-host disease (GVHD) are needed to protect against relapse, treat persistent disease and improve disease-free survival after HSCT.
KW - Graft-versus-host disease
KW - Graft-versus-leukemia reaction
KW - HCT
KW - Immune modulation
KW - Relapse
UR - http://www.scopus.com/inward/record.url?scp=77951149575&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2010.02.005
DO - 10.1016/j.bbmt.2010.02.005
M3 - Review article
C2 - 20152921
AN - SCOPUS:77951149575
SN - 1083-8791
VL - 16
SP - 565
EP - 586
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 5
ER -