A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma

Jpn J Clin Oncol. 2003 Feb;33(2):78-85. doi: 10.1093/jjco/hyg013.

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / pharmacology
  • Adolescent
  • Adult
  • Analysis of Variance
  • Antigens, CD34 / blood
  • Antigens, CD34 / drug effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Colony-Forming Units Assay
  • Cyclophosphamide / therapeutic use*
  • Dose-Response Relationship, Drug
  • Doxorubicin / therapeutic use*
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization / methods*
  • Humans
  • Lenograstim
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged
  • Prednisone / therapeutic use*
  • Recombinant Proteins / administration & dosage*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacology
  • Vincristine / therapeutic use*

Substances

  • Adjuvants, Immunologic
  • Antigens, CD34
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Vincristine
  • Lenograstim
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone

Supplementary concepts

  • CHOP protocol