title: Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect.
abstract: We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB)-derived regulatory T cells (Tregs) that expanded in cultures stimulated with K562 cells modified to express the high-affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3-100 × 10(6) Treg/kg. The median proportion of CD4(+)FoxP3(+)CD127(-) in the infused product was 87% (range, 78%-95%), and we observed no dose-limiting infusional adverse events. Clinical outcomes were compared with contemporary controls (n = 22) who received the same conditioning regimen with sirolimus and mycophenolate mofetil immune suppression. The incidence of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 9% (95% confidence interval [CI], 0-25) vs 45% (95% CI, 24-67) in controls (P = .05). Chronic GVHD at 1 year was zero in Tregs and 14% in controls. Hematopoietic recovery and chimerism, cumulative density of infections, nonrelapse mortality, relapse, and disease-free survival were similar in the Treg recipients and controls. KT64/86-expanded UCB Tregs were safe and resulted in low risk of acute GVHD.
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Hematology, Oncology and Transplantation.
authors.forename: Claudio G
authors.initials: CG
authors.lastname: Brunstein
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Hematology, Oncology and Transplantation.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.affiliation: Department of Laboratory Medicine and Pathology, Molecular and Cellular Therapeutics Facility.
authors.forename: David H
authors.initials: DH
authors.lastname: McKenna
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Pediatric Blood and Marrow Transplantation, and.
authors.forename: Keli L
authors.initials: KL
authors.lastname: Hippen
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Masonic Cancer Center, University of Minnesota, Minneapolis, MN;
authors.forename: Todd E
authors.initials: TE
authors.lastname: DeFor
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Molecular and Cellular Therapeutics Facility.
authors.forename: Darin
authors.initials: D
authors.lastname: Sumstad
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Pediatric Blood and Marrow Transplantation, and.
authors.forename: Julie
authors.initials: J
authors.lastname: Curtsinger
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Pediatric Blood and Marrow Transplantation, and.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Pediatric Blood and Marrow Transplantation, and.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.affiliation: Department of Pathology and Laboratory Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Levine
authors.affiliation: Department of Pathology and Laboratory Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: James L
authors.initials: JL
authors.lastname: Riley
authors.affiliation: Department of Pathology and Laboratory Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; and.
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN; Division of Biostatistics, University of Minnesota, Minneapolis, MN.
authors.forename: Chap
authors.initials: C
authors.lastname: Le
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Hematology, Oncology and Transplantation.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Hematology, Oncology and Transplantation.
authors.forename: Philip B
authors.initials: PB
authors.lastname: McGlave
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Pediatric Blood and Marrow Transplantation, and.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: University of Minnesota Blood and Marrow Transplant Program, Division of Pediatric Blood and Marrow Transplantation, and.
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D005312:Fetal Blood; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007700:Kinetics; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016016:Proportional Hazards Models; D050378:T-Lymphocytes, Regulatory / Q000637:transplantation*; D019172:Transplantation Conditioning / Q000379:methods; D055815:Young Adult