title: Haploidentical stem cell transplantation augmented by CD45RA negative lymphocytes provides rapid engraftment and excellent tolerability.
abstract: BACKGROUND
  Haploidentical donors are being increasingly used for allogeneic hematopoietic cell transplantation (HCT). However, the requisite T-cell depletion results in a profound and often long-lasting immunocompromised state, and donor lymphocyte infusions bring a risk of graft-versus-host disease (GVHD). Naïve T-cells are believed to be among the most alloreactive T-cell subset and can be identified by CD45RA expression. Allogeneic HCT using CD45RA depletion has not been previously described for haploidentical donors.
  
  
  METHODS
  Eight children with relapsed or refractory solid tumors were transplanted following myeloablative conditioning. Each patient received two cell products, one created by CD3 depletion and the other through CD45RA depletion.
  
  
  RESULTS
  Median CD34 recovery was 59.2% with CD45RA depletion, compared to 82.4% using CD3 depletion. Median CD3+ T-cell dose after CD45RA reduction was 99.2 × 10(6)  cells/kg, yet depletion of CD3+ CD45RA+ cells exceeded 4.5 log. CD45RA depletion also resulted in substantial depletion of B-cells (median 2.45 log). All eight patients engrafted within 14 days and rapidly achieved 100% donor chimerism. No acute GVHD or secondary graft failure was observed.
  
  
  CONCLUSIONS
  CD45RA depletion is a novel approach to haploidentical HCT that offers rapid engraftment with minimal risk of GVHD.
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee 38105; Department of Pediatrics, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee 38163.
authors.forename: David R
authors.initials: DR
authors.lastname: Shook
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Triplett
authors.forename: Paul W
authors.initials: PW
authors.lastname: Eldridge
authors.forename: Guolian
authors.initials: G
authors.lastname: Kang
authors.forename: Ashok
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Wing
authors.initials: W
authors.lastname: Leung
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D017493:Leukocyte Common Antigens; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D061349:Unrelated Donors
chemical_list: D017493:Leukocyte Common Antigens
keywords: NK cells BMT; graft versus host disease; immunotherapy; stem cell transplantation