title: Effective purging of autologous hematopoietic stem cells using anti-B-cell monoclonal antibody-coated high-density microparticles prior to high-dose therapy for patients with non-Hodgkin's lymphoma.
abstract: Contamination of hematopoietic stem cells (HSCs) with tumor cells has been associated with increased incidence of relapse in patients with non-Hodgkin's lymphoma following autologous HSC transplantation. Effective purging of tumor cells may improve the results of HSC transplantation, but current methods of purging are technically difficult to perform with large numbers of cells and do not consistently remove all detectable cells. We report a pilot clinical trial in which 10 patients with relapsed B-cell non-Hodgkin's lymphoma received high-dose chemotherapy followed by infusion of autologous HSCs depleted of B-cells by high-density microparticles (HDM) coated with anti-CD19 and anti-CD20 monoclonal antibodies (BCell-HDM). HSCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. In 6 of the 10 patients, B-cells were detectable by immunocytochemical analysis of the apheresis products prior to treatment. Following treatment with the BCell-HDM, no B-cells were detected in the products from 5 of these patients, a result representing a median depletion of >2.2 logs (range, >0.4 to >5.1 logs). The median recovery of nontarget cells postdepletion was 73% for CD34 cells and 78% for CD3+ cells. All patients received high-dose cyclophosphamide, BCNU (carmustine), and etoposide prior to reinfusion of their B-cell-depleted autologous HSCs. The median number of CD34+ cells cryopreserved was 3.6 x 10(6) cells/kg (range, 2.2-10.1 x 10(6) cells/kg). Engraftment was rapid in all cases, with a median time to achieve an absolute neutrophil count of 0.5 x 10(9)/L of 10 days (range, 8-11 days). The median time to achieve a platelet count of 20 x 10(9)/L unsupported by platelet transfusion was 11.5 days (range, 8-17 days). This nonmagnetic negative-depletion technology is simple, rapid, and effective in depleting target cells to undetectable levels, with excellent recovery of nontarget cells.
authors.affiliation: Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA. arnold_freedman@dfci.harvard.edu
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Webb
authors.forename: nathan W
authors.initials: nW
authors.lastname: Friedberg
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.forename: Thomas
authors.initials: T
authors.lastname: Spitzer
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Haddy
authors.initials: H
authors.lastname: Jallow
authors.forename: Helen
authors.initials: H
authors.lastname: Kim
authors.forename: Heather
authors.initials: H
authors.lastname: Houde
authors.forename: Ron
authors.initials: R
authors.lastname: Monroy
authors.forename: Robert
authors.initials: R
authors.lastname: Schmittling
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Freedman
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002469:Cell Separation / Q000379:methods*; D018572:Disease-Free Survival; D006085:Graft Survival; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000592:standards; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000628:therapy*; D008863:Microspheres; D008875:Middle Aged; D010865:Pilot Projects; D055502:Secondary Prevention; D014182:Transplantation, Autologous / Q000379:methods / Q000592:standards
chemical_list: D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte