title: Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts.
abstract: BACKGROUND
  Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HCT). In mice, naive T cells (TN) cause more severe GVHD than memory T cells (TM). We hypothesized that selective depletion of TN from human allogeneic peripheral blood stem cell (PBSC) grafts would reduce GVHD and provide sufficient numbers of hematopoietic stem cells and TM to permit hematopoietic engraftment and the transfer of pathogen-specific T cells from donor to recipient, respectively.
  
  
  METHODS
  In a single-arm clinical trial, we transplanted 35 patients with high-risk leukemia with TN-depleted PBSC grafts following conditioning with total body irradiation, thiotepa, and fludarabine. GVHD prophylactic management was with tacrolimus immunosuppression alone. Subjects received CD34-selected PBSCs and a defined dose of TM purged of CD45RA+ TN. Primary and secondary objectives included engraftment, acute and chronic GVHD, and immune reconstitution.
  
  
  RESULTS
  All recipients of TN-depleted PBSCs engrafted. The incidence of acute GVHD was not reduced; however, GVHD in these patients was universally corticosteroid responsive. Chronic GVHD was remarkably infrequent (9%; median follow-up 932 days) compared with historical rates of approximately 50% with T cell-replete grafts. TM in the graft resulted in rapid T cell recovery and transfer of protective virus-specific immunity. Excessive rates of infection or relapse did not occur and overall survival was 78% at 2 years.
  
  
  CONCLUSIONS
  Depletion of TN from stem cell allografts reduces the incidence of chronic GVHD, while preserving the transfer of functional T cell memory.
  
  
  BACKGROUND
  ClinicalTrials.gov (NCT 00914940).
authors.forename: Marie
authors.initials: M
authors.lastname: Bleakley
authors.forename: Shelly
authors.initials: S
authors.lastname: Heimfeld
authors.forename: Keith R
authors.initials: KR
authors.lastname: Loeb
authors.forename: Lori A
authors.initials: LA
authors.lastname: Jones
authors.forename: Colette
authors.initials: C
authors.lastname: Chaney
authors.forename: Stuart
authors.initials: S
authors.lastname: Seropian
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Franziska
authors.initials: F
authors.lastname: Sommermeyer
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Warren D
authors.initials: WD
authors.lastname: Shlomchik
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000818:Animals; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D051379:Mice; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones