title: Optimization of individualized graft composition: CD3/CD19 depletion combined with CD34 selection for haploidentical transplantation.
abstract: Excessive T-cell depletion (TCD) is a prerequisite for graft manufacturing in haploidentical stem cell (SC) transplantation by using either CD34 selection or direct TCD such as CD3/CD19 depletion.
  
  
  
  To optimize graft composition we compared 1) direct or indirect TCD only, 2) a combination of CD3/CD19-depleted with CD34-selected grafts, or 3) TCD twice for depletion improvement based on our 10-year experience with 320 separations in graft manufacturing and quality control.
  
  
  
  SC recovery was significantly higher (85%, n = 187 vs. 73%, n = 115; p < 0.0001), but TCD was inferior (median log depletion, -3.6 vs. -5.2) for CD3/CD19 depletion compared to CD34 selection, respectively. For end products with less than -2.5 log TCD, a second depletion step led to a successful improvement in TCD. Thawing of grafts showed a high viability and recovery of SCs, but low NK-cell yield. To optimize individualized graft engineering, a calculator was developed to estimate the results of the final graft based on the content of CD34+ and CD3+ cells in the leukapheresis product.
  
  
  
  Finally, calculated splitting of the starting product followed by CD3/19 depletion together with CD34+ graft manipulation may enable the composition of optimized grafts with high CD34+-cell and minimal T-cell content.
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany. sabine.huenecke@kgu.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Huenecke
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bremm
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cappel
authors.affiliation: GMP Development Unit, Institute of Cellular Therapeutics, IFB-TX, Hannover Medical School, Hannover, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Esser
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Quaiser
authors.affiliation: Division for Cell Processing, Institute for Transfusion Medicine and Immunohematology, Goethe-University Frankfurt/Main.|German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Frankfurt/Main, Germany.
authors.forename: Halvard
authors.initials: H
authors.lastname: Bonig
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jarisch
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Soerensen
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Clinic for Pediatric and Adolescent Medicine, University Hospital, Frankfurt, Germany.|GMP Development Unit, Institute of Cellular Therapeutics, IFB-TX, Hannover Medical School, Hannover, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
mesh_terms: D018941:Antigens, CD19 / Q000276:immunology*; D018952:Antigens, CD34 / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007937:Leukapheresis; D008212:Lymphocyte Depletion / Q000379:methods*; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D018941:Antigens, CD19; D018952:Antigens, CD34; D017252:CD3 Complex