title: Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies.
abstract: 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 antithymocyte 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.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA. Robert_Soiffer@dfci.harvard.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lerademacher
authors.forename: Vincent
authors.initials: V
authors.lastname: Ho
authors.forename: Fangyu
authors.initials: F
authors.lastname: Kan
authors.forename: Andrew
authors.initials: A
authors.lastname: Artz
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Steven
authors.initials: S
authors.lastname: Devine
authors.forename: Luis
authors.initials: L
authors.lastname: Isola
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.forename: David L
authors.initials: DL
authors.lastname: Porter
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: Mary
authors.initials: M
authors.lastname: Eapen
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000473:pathology; D019337:Hematologic Neoplasms / Q000517:prevention & control / Q000601:surgery / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D012008:Recurrence; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies