title: Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy.
abstract: OBJECTIVE
  Attempts to increase dose-intensity in clinical practice have been limited by cumulative hematologic toxicity despite the use of hematopoietic growth factors. To address this problem, we designed a study to determine whether four cycles of dose-intensive chemotherapy with carboplatin could be administered in the outpatient setting using granulocyte-macrophage colony-stimulating factor (GM-CSF) and peripheral-blood progenitor cells (PBPCs) that had been harvested before initiation of treatment.
  
  
  METHODS
  An initial cycle (cycle no. 0) of cyclophosphamide 4 g/m2 followed by GM-CSF was used to mobilize PBPCs harvested by leukapheresis for 6 consecutive days. Cycles no. 1 through 4 consisted of outpatient carboplatin 600 mg/m2 and cyclophosphamide 600 mg/m2 followed by GM-CSF 5 micrograms/kg subcutaneously (SC) twice per day every 28 days. In cycle no. 1, PBPC were not reinfused to assess the effects of GM-CSF alone. In cycles no. 2 through 4, PBPCs were reinfused on day 3 in an outpatient setting.
  
  
  RESULTS
  In eight assessable patients, the addition of PBPCs in cycle no. 2 resulted in a significant reduction in the median duration of thrombocytopenia less than 20,000/microL (6.5 v 1 day; P = .016), days to platelets more than 50,000/microL (20.5 v 15 days; P = .020), number of platelet transfusions (five v 1.5; P = .016), and duration of neutropenia (absolute neutrophil count [ANC] < 1,000/microL (7 v 2.5 days; P = .008) when compared with cycle no. 1. Dose-limiting hematologic toxicity, defined as more than 7 days of platelets less than 20,000/microL or ANC less than 500/microL, was observed in four of eight patients during cycle no. 1, but not during cycles no. 2, 3, and 4 of chemotherapy supported by PBPCs (a total of 19 cycles in eight patients). Five of eight patients completed all four cycles of high-dose therapy. Three patients did not complete four cycles due to late thrombocytopenia (n = 2) or tumor progression (n = 1).
  
  
  CONCLUSIONS
  These results indicate a benefit of PBPCs in addition to GM-CSF in alleviating myelosuppression of dose-intensive chemotherapy. Initial collection of PBPCs may allow administration of repetitive cycles of high-dose chemotherapy with acceptable toxicity to outpatients at disease onset.
authors.affiliation: Department of Medicine, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: I
authors.initials: I
authors.lastname: Tepler
authors.forename: S A
authors.initials: SA
authors.lastname: Cannistra
authors.forename: E
authors.initials: E
authors.lastname: Frei
authors.forename: R
authors.initials: R
authors.lastname: Gonin
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson
authors.forename: G
authors.initials: G
authors.lastname: Demetri
authors.forename: J
authors.initials: J
authors.lastname: Niloff
authors.forename: H
authors.initials: H
authors.lastname: Goodman
authors.forename: H
authors.initials: H
authors.lastname: Muntz
authors.forename: M
authors.initials: M
authors.lastname: Muto
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D015925:Cryopreservation; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000628:therapy
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D016190:Carboplatin