title: Single high doses of cyclophosphamide enable the collection of high numbers of hemopoietic stem cells from the peripheral blood.
abstract: We used single high doses of cyclophosphamide (4 g/m2) to produce rebound increases in peripheral blood (PB) stem cells (PBSC) during recovery from myelosuppression, enabling their collection by apheresis for later autotransplantation. Thirty-three courses of cyclophosphamide were given to 30 patients with malignant lymphoma, multiple myeloma, or solid tumors. The neutrophil count was less than 0.5 x 10(9)/liter for a mean of 6.9 days (median 7 days), and fever occurred in 17 of 33 courses. Positive blood cultures occurred in two patients, one of whom died. The mean peak level of PB granulocyte-macrophage colony-forming units (CFU-GM) was 1517 x 10(3)/liter (median 2447 x 10(3)/liter), a 14-fold increase above the mean in normal subjects. The peak occurred at a mean of 16.6 days (median 16 days) after cyclophosphamide, generally coinciding with the time to reach 1.0 x 10(9) neutrophils per liter. Normal or minimally involved bone marrow and a rapid rise in leukocyte count during recovery were independent variables correlated to the peak of the rebound increase in PB CFU-GM levels. Previous chemotherapy and the duration of neutropenia were additional independent variables in the group with peak PB CFU-GM levels of greater than 1000 x 10(3)/liter. The mean total CFU-GM collected after a mean of five aphereses was 43.8 x 10(4)/kg body weight (BW) (median 35.5 x 10(4)/kg BW), significantly correlated with the mononuclear cell yield. We conclude that single 4 g/m2 doses of cyclophosphamide effectively produce high levels of PBSC, particularly but not exclusively in patients with normal or minimally involved bone marrow and who have not had intensive recent chemotherapy.
authors.affiliation: Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia.
authors.forename: L B
authors.initials: LB
authors.lastname: To
authors.forename: K M
authors.initials: KM
authors.lastname: Shepperd
authors.forename: D N
authors.initials: DN
authors.lastname: Haylock
authors.forename: P G
authors.initials: PG
authors.lastname: Dyson
authors.forename: P
authors.initials: P
authors.lastname: Charles
authors.forename: D L
authors.initials: DL
authors.lastname: Thorp
authors.forename: B M
authors.initials: BM
authors.lastname: Dale
authors.forename: G W
authors.initials: GW
authors.lastname: Dart
authors.forename: M M
authors.initials: MM
authors.lastname: Roberts
authors.forename: R E
authors.initials: RE
authors.lastname: Sage
mesh_terms: D000328:Adult; D001781:Blood Component Removal; D002452:Cell Count; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006098:Granulocytes / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007958:Leukocyte Count; D008223:Lymphoma / Q000097:blood* / Q000188:drug therapy; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy; D010976:Platelet Count
chemical_list: D003520:Cyclophosphamide