Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor for peripheral blood progenitor cell mobilization.
This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 microg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 microg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached > or = 2 x 10(9)/L; leukapheresis was continued until acquisition of a target dose of > or = 5 x 10(6) CD34+ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91% required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69% of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 x 10(6) CD34 cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 x 10(6) cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after high-dose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 x 10(9)/L and a platelet count of 20 x 10(9)/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.
Gajewski
James L
JL
University of Texas M. D. Anderson Cancer Center, Department of Blood and Marrow Transplantation, Houston 77030-4095, USA. JGajewsk@mail.mdanderson.org
Rondon
Gabriela
G
Donato
Michele L
ML
Anderlini
Paolo
P
Korbling
Martin
M
Ippoliti
Cindy
C
Benyunes
Mark
M
Miller
Langdon L
LL
LaTemple
Denise
D
Jones
Denny
D
Ashby
Mark
M
Hellmann
Sue
S
Durett
April
A
Lauppe
Jo
J
Geisler
Deborah
D
Khouri
Issa F
IF
Giralt
Sergio A
SA
Andersson
Borje
B
Ueno
Naoto T
NT
Champlin
Richard
R
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D005260:Female; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods* / Q000592:standards; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D007700:Kinetics; D007937:Leukapheresis / Q000592:standards; D007958:Leukocyte Count; D008875:Middle Aged; D013926:Thrombopoietin / Q000008:administration & dosage* / Q000276:immunology
D018952:Antigens, CD34; D007518:Isoantibodies; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin