title: Beneficial impact of peripheral blood progenitor cells in patients with metastatic breast cancer treated with high-dose chemotherapy plus granulocyte-macrophage colony-stimulating factor. A randomized trial.
abstract: BACKGROUND
  This study compared the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with peripheral blood-derived hematopoietic progenitor cells (PBP) as support for patients receiving high-dose chemotherapy and assessed the adequacy of these strategies as alternatives to autologous bone marrow rescue.
  
  
  METHODS
  The authors studied patients with metastatic breast carcinoma who had a major response to conventional chemotherapy or had achieved a complete remission by surgical resection of all known metastases. They were treated with carboplatin 1500 mg/m2, etoposide 1200 mg/m2, and cyclophosphamide 5.0 g/m2. Before this high-dose chemotherapy, the patients had been randomly assigned to one of two hematopoietic support strategies: GM-CSF alone (Group 1) or GM-CSF-primed PBP and GM-CSF (Group 2). Autologous bone marrow was harvested from all patients for use only in the event of persistent pancytopenia with marrow aplasia on day 15.
  
  
  RESULTS
  A total of 18 patients were treated. Randomization was halted after the initial 10 patients because of the significant advantages for patients in Group 2 in comparison with those in Group 1 in regard to (1) the median number of days to absolute neutrophil count 0.5 x 10(9)/l (12 versus 21) and platelet count to 50 x 10(9)/l (13 versus 23), (2) platelet transfusions (3 versus 15.5), and (3) episodes of neutropenic sepsis (0 versus 4, respectively). One patient in Group 1 died from treatment-related complications. All patients in Group 1 required bone marrow reinfusion. No patient in Group 2 required bone marrow reinfusion, and no early mortality was observed in this group. Eight subsequent patients were treated with PBP and GM-CSF (Group 3). This group was more heavily pretreated than Groups 1 or 2 and had a slower hematologic recovery than Group 2. However, none of these patients required bone marrow reinfusion. The four patients in Group 1 that did not have early bone marrow rescue all had neutrophil counts of 0.0 on day 15. For Groups 2 and 3, the neutrophil counts on day 15 ranged from 0.3-2.1 x 10(9)/l (median, 1.9) and from 0.2-2.1 x 10(9)/l (median 0.6), respectively.
  
  
  CONCLUSIONS
  The use of PBP plus GM-CSF accelerated hematologic recovery after this chemotherapeutic regimen compared with GM-CSF alone; there were reduced morbidity and platelet transfusion requirements. Recovery was sufficiently rapid that PBP were an acceptable alternative to autologous bone marrow transplantation in patients receiving high-dose carboplatin, etoposide, and cyclophosphamide.
authors.affiliation: Breast and Gynecological Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
authors.forename: A
authors.initials: A
authors.lastname: Kritz
authors.forename: J P
authors.initials: JP
authors.lastname: Crown
authors.forename: R J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: L M
authors.initials: LM
authors.lastname: Reich
authors.forename: G
authors.initials: G
authors.lastname: Heller
authors.forename: M P
authors.initials: MP
authors.lastname: Moore
authors.forename: N
authors.initials: N
authors.lastname: Hamilton
authors.forename: T J
authors.initials: TJ
authors.lastname: Yao
authors.forename: R T
authors.initials: RT
authors.lastname: Heelan
authors.forename: J G
authors.initials: JG
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000628:therapy*; D013921:Thrombocytopenia / Q000628:therapy*
chemical_list: D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D016190:Carboplatin