title: High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning.
abstract: OBJECTIVE
  To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies.
  
  
  METHODS
  We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content.
  
  
  RESULTS
  Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 10(8) CD8 cells per kilogram optimally segregated patients receiving CD8(hi) and CD8(lo) grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8(hi) graft, whereas approximately half of younger donors provided CD8(hi) grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8(lo) doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8(hi) doses (P = .03), but not for recipients of younger unrelated donor CD8(lo) grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors.
  
  
  CONCLUSIONS
  Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT.
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. ran.reshef@uphs.upenn.edu.
authors.forename: Ran
authors.initials: R
authors.lastname: Reshef
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Austin P
authors.initials: AP
authors.lastname: Huffman
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Amy
authors.initials: A
authors.lastname: Gao
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Marlise R
authors.initials: MR
authors.lastname: Luskin
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Noelle V
authors.initials: NV
authors.lastname: Frey
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Saar I
authors.initials: SI
authors.lastname: Gill
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Hexner
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Taku
authors.initials: T
authors.lastname: Kambayashi
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Alison W
authors.initials: AW
authors.lastname: Loren
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Selina M
authors.initials: SM
authors.lastname: Luger
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: James K
authors.initials: JK
authors.lastname: Mangan
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Sunita D
authors.initials: SD
authors.lastname: Nasta
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Lee P
authors.initials: LP
authors.lastname: Richman
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sell
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Vonderheide
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mick
authors.affiliation: All authors: Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
authors.forename: David L
authors.initials: DL
authors.lastname: Porter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes; D046148:Donor Selection; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D019653:Myeloablative Agonists