Granulocyte colony-stimulating factor as an adjunct to induction chemotherapy for adult acute lymphoblastic leukemia--a randomized phase-III study

Blood. 1997 Jul 15;90(2):590-6.

Abstract

Because of the recommendation to avoid the concomitant administration of growth factors and chemotherapy, there is only limited information on colony-stimulating factor (CSF) therapy in acute lymphoblastic leukemia (ALL) induction protocols, in which cytotoxic drugs are administered in divided doses over a prolonged period of time, thus requiring a simultaneous administration of growth factors and chemotherapy. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF; filgrastim) as an adjunct to phase I of induction chemotherapy for adult ALL. Patients (n = 53) were randomized to receive no growth factor or G-CSF (5 microg/kg/d subcutaneously) starting on day 2 of chemotherapy consisting of daunorubicin (45 mg/m2) and vincristine (1.5 mg/m2) on days 1, 8, 15, and 22; L-asparaginase (2500 U/m2) on days 1 through 14; and prednisone (60 mg/m2) on days 1 through 28. A total of 25 patients in the G-CSF group and 26 patients in the control arm fulfilled the inclusion criteria of the study. G-CSF markedly ameliorated neutropenia because the median proportion of days with neutropenia less than 1,000/microL was 29% in the G-CSF group as compared with 84% in the control arm (P < .00005). The median time to reach absolute neutrophil counts (ANC) > or = 1,000/microL was 16 days in G-CSF patients and 26 days in controls (P < .001). More importantly, G-CSF significantly reduced the incidence of febrile neutropenia (12% v 42% in controls, P < .05) and documented infections (40% v 77%, P < .05). No significant differences were found with regard to requirements for red blood cell transfusions and platelet concentrates. A total of 24 of 25 (96%) patients in the G-CSF group and 20 of 25 (80%) evaluable control patients had complete remission after phase I of induction therapy. We conclude that G-CSF can be safely administered as an adjunct to induction therapy of ALL and is clinically beneficial by ameliorating neutropenia and reducing infectious complications.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Blood Transfusion
  • Daunorubicin / administration & dosage
  • Erythrocyte Count
  • Female
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Neutropenia / prevention & control
  • Neutrophils
  • Platelet Count
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Prednisone / administration & dosage
  • Remission Induction
  • Survival Rate
  • Vincristine / administration & dosage

Substances

  • Granulocyte Colony-Stimulating Factor
  • Vincristine
  • Asparaginase
  • Prednisone
  • Daunorubicin