title: Transplant dose of CD34(+) and CD3(+) cells predicts outcome in patients with haematological malignancies undergoing T cell-depleted peripheral blood stem cell transplants with delayed donor lymphocyte add-back.
abstract: We sought to optimize and standardize stem cell and lymphocyte doses of T cell-depleted peripheral blood stem cell transplants (T-PBSCT), using delayed add-back of donor T cells (DLI) to prevent relapse and enhance donor immune recovery. Fifty-one patients with haematological malignancies received a T-PBSCT from an HLA-identical sibling, followed by DLI of 1 x 10(7) and 5 x 10(7) CD3(+) cells/kg on d +45 and +100 respectively. Twenty-four patients were designated as standard risk and twenty-seven patients with more advanced leukaemia were designated as high risk. Median recipient age was 38 years (range 10-56). Median (range) of CD34(+) and CD3(+) cell transplant doses were 4.6 (2.3-10.9) x 10(6)/kg and 0.83 (0.38-2) x 10(5)/kg respectively. The cumulative probability of acute GVHD was 39%. No patient died from GVHD or its consequences. The probability of developing chronic GVHD was 54% (18% extensive). The probability of relapse was 12% for the standard-risk patients and 66% for high-risk patients. In multivariate analysis, the risk factors for lower disease-free survival and overall survival were high-risk disease, CD34(+) dose < 4.6 x 10(6)/kg and CD3(+) dose < 0.83 x 10(5)/kg. Predictive factors for chronic GVHD were a T-cell dose at transplant > 0.83 x 10(5) CD3(+) cells/kg. These results further define the impact of CD34 and CD3 cell dose on transplant outcome and show that careful dosing of stem cells and lymphocytes may permit the control and optimization of transplant outcome.
authors.affiliation: Stem Cell Transplantation Unit, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: R
authors.initials: R
authors.lastname: Nakamura
authors.forename: E
authors.initials: E
authors.lastname: Bahceci
authors.forename: E J
authors.initials: EJ
authors.lastname: Read
authors.forename: S F
authors.initials: SF
authors.lastname: Leitman
authors.forename: C S
authors.initials: CS
authors.lastname: Carter
authors.forename: R
authors.initials: R
authors.lastname: Childs
authors.forename: C E
authors.initials: CE
authors.lastname: Dunbar
authors.forename: R
authors.initials: R
authors.lastname: Gress
authors.forename: R
authors.initials: R
authors.lastname: Altemus
authors.forename: N S
authors.initials: NS
authors.lastname: Young
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology*; D001804:Blood Transfusion, Autologous; D017252:CD3 Complex / Q000276:immunology*; D002648:Child; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D008232:Lymphoproliferative Disorders / Q000601:surgery*; D008875:Middle Aged; D011336:Probability; D013997:Time Factors
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex