title: Multicyclic, dose-intensive chemotherapy supported by sequential reinfusion of hematopoietic progenitors in whole blood.
abstract: OBJECTIVE
  To support multicyclic, dose-intensive chemotherapy, we assessed the effects of reinfusing hematopoietic progenitors collected at each cycle in leukapheresis product or whole blood.
  
  
  METHODS
  Twenty-five patients with small-cell lung cancer (SCLC) were treated with six cycles of ifosfamide, carboplatin, and etoposide (ICE) with granulocyte colony-stimulating factor (G-CSF) 300 micrograms/d subcutaneously (SC) on days 4 to 15. Hematopoietic progenitors collected during each cycle were reinfused on day 3 of the next cycle. Cohort 1 (n = 6) was treated every 3 weeks, with leukapheresis after 2 weeks and cryopreservation of the leukapheresis product. Chemotherapy was given if the WBC count was > or = 3 x 10(9)/L and platelet count > or = 100 x 10(9)/L. Cohort 2 (n = 7) was treated every 2 weeks, with leukapheresis on day 1 of the next cycle and storage of the leukapheresis product at 4 degrees C. Cohort 3 (n = 12) was treated every 2 weeks, with 500 to 750 mL of blood drawn by venesection on day 1 of the next cycle and stored at 4 degrees C. In cohorts 2 and 3, chemotherapy was given if the WBC count was > or = 3 x 10(9)/L and platelet count > or = 30 x 10(9)/L. Blood and leukapheresis products were assayed for hematopoietic progenitors.
  
  
  RESULTS
  ICE chemotherapy with G-CSF was effective in mobilizing blood progenitors (median, 120-fold). Long-term cultures showed no evidence of stem-cell depletion. The cytotoxic dose-intensity of standard every-4-weeks ICE is 100%. In the first three cycles, it was 134% (median) in cohort 1 and 200% in cohorts 2 and 3 (P < .0001). Toxicity and supportive care requirements were not increased.
  
  
  CONCLUSIONS
  The dose-intensity of ICE chemotherapy can be doubled by reinfusing hematopoietic progenitors collected by leukapheresis or venesection and stored at 4 degrees C.
authors.affiliation: Department of Medical Oncology, Christie Hospital, Manchester, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Pettengell
authors.forename: P J
authors.initials: PJ
authors.lastname: Woll
authors.forename: N
authors.initials: N
authors.lastname: Thatcher
authors.forename: T M
authors.initials: TM
authors.lastname: Dexter
authors.forename: N G
authors.initials: NG
authors.lastname: Testa
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001804:Blood Transfusion, Autologous; D016190:Carboplatin / Q000008:administration & dosage; D018288:Carcinoma, Small Cell / Q000097:blood / Q000401:mortality / Q000628:therapy*; D002423:Cause of Death; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007937:Leukapheresis; D008175:Lung Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017713:Platelet Transfusion
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide