TY - JOUR
T1 - Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies
AU - Soiffer, Robert J.
AU - LeRademacher, Jennifer
AU - Ho, Vincent
AU - Kan, Fangyu
AU - Artz, Andrew
AU - Champlin, Richard E.
AU - Devine, Steven
AU - Isola, Luis
AU - Lazarus, Hillard M.
AU - Marks, David I.
AU - Porter, David L.
AU - Waller, Edmund K.
AU - Horowitz, Mary M.
AU - Eapen, Mary
PY - 2011/6/23
Y1 - 2011/6/23
N2 - The success of reduced intensity conditioning (RIC) transplantation is largely dependent on alloimmune effects. It is critical to determine whether immune modulation with anti-T-cell antibody infusion abrogates the therapeutic benefits of transplantation.We examined 1676 adults undergoing RIC transplantation for hematologic malignancies. All patients received alkylating agent plus fludarabine; 792 received allografts from a human leukocyte antigen-matched sibling, 884 from a 7 or 8 of 8 HLA-matched unrelated donor. Using Cox regression, outcomes after in vivo T-cell depletion (n = 584 anti-thymocyte globulin [ATG]; n = 213 alemtuzumab) were compared with T cell-replete (n = 879) transplantation. Grade 2 to 4 acute GVHD was lower with alemtuzumab compared with ATG or T cell-replete regimens (19% vs 38% vs 40%, P < .0001) and chronic GVHD, lower with alemtuzumab, and ATG regimens compared with T-replete approaches (24% vs 40% vs 52%, P < .0001). However, relapse was more frequent with alemtuzumab and ATG compared with T cell-replete regimens (49%, 51%, and 38%, respectively, P < .001). Disease-free survival was lower with alemtuzumab and ATG compared with T cell-replete regimens (30%, 25%, and 39%, respectively, P < .001). Corresponding probabilities of overall survival were 50%, 38%, and 46% (P = .008). These data suggest adopting a cautious approach to routine use of in vivo T-cell depletion with RIC regimens.
AB - The success of reduced intensity conditioning (RIC) transplantation is largely dependent on alloimmune effects. It is critical to determine whether immune modulation with anti-T-cell antibody infusion abrogates the therapeutic benefits of transplantation.We examined 1676 adults undergoing RIC transplantation for hematologic malignancies. All patients received alkylating agent plus fludarabine; 792 received allografts from a human leukocyte antigen-matched sibling, 884 from a 7 or 8 of 8 HLA-matched unrelated donor. Using Cox regression, outcomes after in vivo T-cell depletion (n = 584 anti-thymocyte globulin [ATG]; n = 213 alemtuzumab) were compared with T cell-replete (n = 879) transplantation. Grade 2 to 4 acute GVHD was lower with alemtuzumab compared with ATG or T cell-replete regimens (19% vs 38% vs 40%, P < .0001) and chronic GVHD, lower with alemtuzumab, and ATG regimens compared with T-replete approaches (24% vs 40% vs 52%, P < .0001). However, relapse was more frequent with alemtuzumab and ATG compared with T cell-replete regimens (49%, 51%, and 38%, respectively, P < .001). Disease-free survival was lower with alemtuzumab and ATG compared with T cell-replete regimens (30%, 25%, and 39%, respectively, P < .001). Corresponding probabilities of overall survival were 50%, 38%, and 46% (P = .008). These data suggest adopting a cautious approach to routine use of in vivo T-cell depletion with RIC regimens.
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U2 - 10.1182/blood-2011-01-332007
DO - 10.1182/blood-2011-01-332007
M3 - Article
C2 - 21464372
AN - SCOPUS:79959496711
SN - 0006-4971
VL - 117
SP - 6963
EP - 6970
JO - Blood
JF - Blood
IS - 25
ER -