title: A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma.
abstract: BACKGROUND
  Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown.
  
  
  METHODS
  To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level.
  
  
  RESULTS
  The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients.
  
  
  CONCLUSIONS
  The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.
authors.affiliation: Hematology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Takeyama
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kasai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuya
authors.forename: Fumio
authors.initials: F
authors.lastname: Kawano
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Masaki
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Sasaki
authors.forename: Takaaki
authors.initials: T
authors.lastname: Chou
authors.forename: Toshiya
authors.initials: T
authors.lastname: Yokozawa
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D018952:Antigens, CD34 / Q000097:blood / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D000078224:Lenograstim; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D014750:Vincristine / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D000078224:Lenograstim; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone