title: Ex vivo T-cell-depleted allogeneic stem cell transplantation for hematologic malignancies: The search for an optimum transplant T-cell dose and T-cell add-back strategy.
abstract: T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 104/kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 107/kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT.
  
  
  
  Two hundred seventeen consecutive patients (age range, 10-75 years) with hematologic malignancy (excluding chronic leukemias) underwent ex vivo TCD SCT from HLA-identical sibling donors from 1994-2015. Ninety-four patients had standard-risk disease (first remission acute leukemia [AL] and early stage myelodysplastic syndromes [MDS]) and 123 had high-risk disease (AL beyond first complete remission, advanced MDS or refractory B-cell malignancy).
  
  
  
  Median follow-up was 8.5 years. At 20 years post-SCT, overall survival (OS) was 40%, nonrelapse mortality (NRM) was 27% and relapse incidence was 39%. Factors affecting outcome in multivariate analysis were transplantation era, with OS increasing from 38% in the period 1994-2000 to 58% in 2011-2015, disease risk (hazard ratio [HR], 1.68 for high risk) and increasing age (HR, 1.19 per decade). Neither the T-cell dose or the add back of T cells in the first 100 days had any effect on OS, NRM and relapse.
  
  
  
  Outcomes for TCD SCT have greatly improved. However, our data do not support the need to precisely manipulate transplant CD3+ T-cell dose provided at least 3-log depletion is achieved or the use of T-cell add-back. Future improvements for TCD SCT await better strategies to prevent relapse, especially in high-risk recipients.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Prathima
authors.initials: P
authors.lastname: Anandi
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Sawa
authors.initials: S
authors.lastname: Ito
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Muranski
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Puja D
authors.initials: PD
authors.lastname: Chokshi
authors.affiliation: Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Noelle
authors.initials: N
authors.lastname: Watters
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Upneet
authors.initials: U
authors.lastname: Chawla
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Hensel
authors.affiliation: Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Stroncek
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: barrettj@nhlbi.nih.gov.
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex
keywords: CD3 dose; CD34 dose; T-cell depletion; allogeneic stem cell transplant; cell processing; donor lymphocyte infusion