title: Characteristics of CliniMACS® System CD34-enriched T cell-depleted grafts in a multicenter trial for acute myeloid leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303.
abstract: Eight centers participated in the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303 to determine the effect of extensive T cell depletion (TCD) on the outcome of HLA matched sibling donor transplantation for acute myeloid leukemia. One goal of the study was to determine if TCD could be performed uniformly among study sites. TCD was achieved using the CliniMACS(®) CD34 Reagent System for CD34 enrichment. Processed grafts needed to contain ≥ 2.0 × 10(6) CD34(+)cells/kg with a target of 5.0 × 10(6) CD34(+) cells/kg and <10(5) CD3(+) T cells/kg. Up to 3 collections were allowed to achieve the minimum CD34(+) cell dose. In total, 86 products were processed for 44 patients. Differences in the starting cell products between centers were seen in regard to total nucleated cells, CD34(+) cells, and CD3(+) T cells, which could in part be ascribed to a higher dose of granulocyte-colony stimulating factor used for mobilization early in the trial. Differences between centers in processing outcomes were minimal and could be ascribed to starting cell parameters or to differences in graft analysis methods. Multivariate analysis showed that CD34(+) cell recovery (66.1% ± 20.3%) was inversely associated with the starting number of CD34(+) cells (P = .02). Median purity of the CD34 enriched fraction was 96.7% (61.5%-99.8%) with monocytes and B cells the most common impurity. All patients received the minimum CD34(+) cell dose, and 39 patients (89%) came within 10% or exceeded the target CD34(+) cell dose without exceeding the maximum T cell dose. All patients proceeded to transplantation and all achieved initial engraftment. Products processed at multiple centers using the CliniMACS System for CD34 enrichment were comparably and uniformly highly enriched for CD34(+) cells, with good CD34(+) cell recovery and very low CD3(+) T cell content.
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. ckeever@mcw.edu
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Keever-Taylor
authors.forename: Steven M
authors.initials: SM
authors.lastname: Devine
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Adam
authors.initials: A
authors.lastname: Mendizabal
authors.forename: Shelly
authors.initials: S
authors.lastname: Carter
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Pasquini
authors.forename: Parameswaran N
authors.initials: PN
authors.lastname: Hari
authors.forename: Anthony
authors.initials: A
authors.lastname: Stein
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: Charles
authors.initials: C
authors.lastname: Linker
authors.forename: Steven C
authors.initials: SC
authors.lastname: Goldstein
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
mesh_terms: D018952:Antigens, CD34 / Q000276:immunology*; D001781:Blood Component Removal / Q000379:methods*; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000276:immunology; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018189:Immunomagnetic Separation; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D015999:Multivariate Analysis; D035781:Siblings; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex; D016179:Granulocyte Colony-Stimulating Factor