title: Stem cell function and engraftment is not affected by "in vivo purging" with rituximab for autologous stem cell treatment for patients with low-grade non-Hodgkin's lymphoma.
abstract: The chimeric anti-CD20 monoclonal antibody rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) has recently been approved by the US Food and Drug Administration as single-agent treatment of relapsed/refractory low-grade or follicular non-Hodgkin's lymphoma. Initial results from the pivotal clinical trial revealed that response rates to rituximab were higher in patients who previously had high-dose therapy and autologous stem cell transplantation. We have initiated a clinical trial that combines the use of rituximab with high-dose chemotherapy followed by autologous stem cell transplantation for patients with chemosensitive relapsed follicular small cleaved or mantle cell lymphoma. A unique feature of this study is that in addition to eight maintenance infusions of rituximab after autologous stem cell transplantation, patients also received rituximab 375 mg/m2 2 days before a granulocyte colony-stimulating factor-mobilized stem cell collection as "in vivo purge." We report on preliminary results demonstrating the safety and efficacy of the in vivo purge on 10 patients undergoing stem cell mobilization, nine of whom have already undergone transplantation. The peripheral blood CD34+ counts were 14.92 and 20 x 10(6)/L on day 4 and day 5, respectively, of the stem cell mobilization with granulocyte colony-stimulating factor. This compares with 11.7 and 11.8 x 10(6)/L, respectively, for the control population. The median CD34 stem cell yield in the graft collection was 3.7 x 10(6)/kg in patients receiving rituximab in vivo purge compared with 3.1 x 10(6)/kg in the control population. The target stem cell collection was successfully collected in six of 10 patients in a 1-day single large-volume leukapheresis collection, while two patients required 2 days and the last two patients required 3 days. Functional assays revealed the stem cell colony-forming unit-granulocyte monocyte and burst-forming unit-erythrocyte to be 55 and 44 colonies per plate, respectively, for the patients receiving the in vivo rituximab purge. This compares favorably with 37 and 38.5 colonies per plate, respectively, for the control population. Neutrophil engraftment took a median of 11 days for both cohorts; platelet independence was achieved in 8 days compared with 10 days for the control population. The median number of platelet transfusions was two for patients receiving rituximab and 2.5 for the control group. Assessment of serum cytokines immediately before the rituximab infusion during the stem cell mobilization and immediately after revealed a twofold to sevenfold increase in interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6. The polymerase chain reaction analysis for minimal residual disease in stem cell collections and in peripheral blood and bone marrow samples of these patients will help to determine the efficacy of rituximab in vivo purge on disease progression.
authors.affiliation: Advanced Therapeutics Program, Toronto Sunnybrook Regional Cancer Center, Sunnybrook Health Sciences Centre, University of Toronto, Ontario.
authors.forename: R
authors.initials: R
authors.lastname: Buckstein
authors.forename: K
authors.initials: K
authors.lastname: Imrie
authors.forename: D
authors.initials: D
authors.lastname: Spaner
authors.forename: A
authors.initials: A
authors.lastname: Potichnyj
authors.forename: J B
authors.initials: JB
authors.lastname: Robinson
authors.forename: S
authors.initials: S
authors.lastname: Nanji
authors.forename: N
authors.initials: N
authors.lastname: Pennel
authors.forename: M
authors.initials: M
authors.lastname: Reis
authors.forename: P
authors.initials: P
authors.lastname: Pinkerton
authors.forename: I
authors.initials: I
authors.lastname: Dubé
authors.forename: K
authors.initials: K
authors.lastname: Hewitt
authors.forename: N L
authors.initials: NL
authors.lastname: Berinstein
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016465:Bone Marrow Purging; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D018365:Neoplasm, Residual; D000069283:Rituximab; D016879:Salvage Therapy; D014182:Transplantation, Autologous
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D000069283:Rituximab