title: Positively selected autologous blood CD34+ cells and unseparated peripheral blood progenitor cells mediate identical hematopoietic engraftment after high-dose VP16, ifosfamide, carboplatin, and epirubicin.
abstract: To investigate the feasibility of peripheral blood CD34+ cell selection and to analyze CD34+ cell-mediated engraftment after high-dose chemotherapy, we performed a phase I/II trial in 21 patients with advanced malignancies. The rationale for the selection of CD34+ cells from peripheral blood progenitor cell (PBPC) collections is based on the observation that contaminating tumor cells can be depleted approximately 3 logs using this procedure. CD34+ cells from chemotherapy+granulocyte colony-stimulating factor-mobilized PBPCs were positively selected with an avidin-biotin immunoadsorption column (CEPRATE SC system). One leukapheresis product with a median number of 2.8 x 10(6) CD34+ cells/kg was labeled with a biotinylated anti-CD34 monoclonal antibody and subsequently processed over the column. The yield of selected CD34+ cells was 73% +/- 24.6%. The purity of the CD34+ cell fraction was 61.4% +/- 19.7%. CD34+ cells were shown to represent predominantly committed progenitors coexpressing CD33, CD38, and HLA-DR molecules (lin+). They gave rise to myeloid as well as erythroid and multilineage colonies in vitro. In addition, positively selected CD34+ cells also comprised early hematopoietic progenitor cells, as shown by the presence of CD34+/lin- cells. Transfusion of positively selected CD34+ cells (2.5 x 10(6) CD34+/kg; range, 0.45 to 5.1) after high-dose VP16 (1,500 mg/m2), ifosfamide (12 g/m2), carboplatin (750 mg/m2), and epirubicin (150 mg/m2) (VIC-E) in 15 patients resulted in a rapid and stable engraftment of hematopoiesis without any adverse events. As compared with 13 historical control patients reconstituted with a comparable number of unseparated PBPCs, time to neutrophil and platelet recovery was identical in both groups (absolute neutrophil count > 500/microL, day + 12; platelet count > 50,000/microL, day + 15). These data indicate that autologous peripheral blood CD34+ cells and unseparated PBPCs mediate identical reconstitution of hematopoiesis after high-dose VIC-E chemotherapy. Because positive selection of CD34+ cells from mobilized blood results in a median 403-fold depletion of T cells, allogeneic CD34+ cells from mobilized blood should be investigated as an alternative to bone marrow cells for allotransplantation.
authors.affiliation: Department of Hematology/Oncology, Albert Ludwigs University Freiburg Medical Center, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Brugger
authors.forename: R
authors.initials: R
authors.lastname: Henschler
authors.forename: S
authors.initials: S
authors.lastname: Heimfeld
authors.forename: R J
authors.initials: RJ
authors.lastname: Berenson
authors.forename: R
authors.initials: R
authors.lastname: Mertelsmann
authors.forename: L
authors.initials: L
authors.lastname: Kanz
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000097:blood*; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001761:Bleomycin / Q000008:administration & dosage; D001804:Blood Transfusion, Autologous; D001943:Breast Neoplasms / Q000097:blood / Q000628:therapy; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000097:blood / Q000628:therapy; D003131:Combined Modality Therapy; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D011237:Predictive Value of Tests; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D014750:Vincristine; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide