title: Recombinant human thrombopoietin augments mobilization of peripheral blood progenitor cells for autologous transplantation.
abstract: This study assessed the ability of various schedules of recombinant human thrombopoietin (rhTPO) to enhance mobilization of peripheral blood progenitor cells (PBPCs) in 134 patients with cancer undergoing high-dose chemotherapy and autologous PBPC transplantation. Patients received the study drug on days 1, 3, and 5 before initiation of granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/day on day 5 and pheresis starting on day 9. Randomly assigned treatments on days 1, 3, and 5 were: group 1 (n=27) placebo, placebo, rhTPO 1.5 microg/kg; group 2 (n=27) rhTPO 1.5 microg/kg, placebo, placebo; groups 3 (n=28) and 4 (n=22) rhTPO 0.5 microg/kg on all 3 treatment days; and group 5 (n=30) placebo on all 3 treatment days. After high-dose chemotherapy and PBPC transplantation, groups 1 through 4 received rhTPO 1.5 microg/kg days 0, +2, +4, and +6 with either G-CSF 5 microg/kg/day (groups 1-3) or granulocyte-macrophage colony-stimulating factor 250 microg/m(2)/day (group 4). Group 5 received placebo plus G-CSF 5 microg/kg/day. The addition of rhTPO to G-CSF increased median CD34+ cell yield/pheresis in cohorts in which rhTPO was started before day 5, with higher yields in groups 2 (2.67 x 10(6)/kg) and groups 3 and 4 (3.10 x 10(6)/kg) than in group 1 (1.86 x 10(6)/kg) or group 5 (1.65 x 10(6)/kg) (P=.006 across groups). Comparing rhTPO to placebo, higher percentages of patients achieved the minimum yield of CD34+ > or =2 x 10(6)/kg (92% v 75%; P=.050) as well as the target yield of CD34+ > or =5 x 10(6)/kg (73% v 46%; P= .041). rhTPO-treated patients required fewer phereses to achieve minimum (P= .011) and target (P= .015) CD34+ cell values. rhTPO given after transplantation did not speed platelet recovery. No neutralizing antibodies were observed. We conclude that rhTPO can safely enhance mobilization of PBPC, reduce the number of leukapheresis, and allow more patients to meet minimal cell yield requirements to receive high-dose chemotherapy with PBPC transplantation.
authors.affiliation: Department of Hematology/Oncology, University of California-San Francisco, 400 Parnassus Avenue, Room A502, San Francisco, CA 94143, USA. linkerc@medicine.ucsf.edu
authors.forename: Charles
authors.initials: C
authors.lastname: Linker
authors.forename: Paolo
authors.initials: P
authors.lastname: Anderlini
authors.forename: Roger
authors.initials: R
authors.lastname: Herzig
authors.forename: Neal
authors.initials: N
authors.lastname: Christiansen
authors.forename: George
authors.initials: G
authors.lastname: Somlo
authors.forename: William
authors.initials: W
authors.lastname: Bensinger
authors.forename: Joseph
authors.initials: J
authors.lastname: Fay
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Lynch
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Goodnough
authors.forename: Mark
authors.initials: M
authors.lastname: Ashby
authors.forename: Mark C
authors.initials: MC
authors.lastname: Benyunes
authors.forename: Dennie V
authors.initials: DV
authors.lastname: Jones
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Yang
authors.forename: Langdon L
authors.initials: LL
authors.lastname: Miller
authors.forename: Charles
authors.initials: C
authors.lastname: Weaver
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007937:Leukapheresis; D008223:Lymphoma / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013926:Thrombopoietin / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013926:Thrombopoietin