Mobilization of peripheral blood stem cells with paclitaxel and rhG-CSF in high-risk breast cancer patients.
Preclinical studies have demonstrated the rapid and efficient mobilization of hematopoietic peripheral blood stem cells (PBSC) in a mouse model using the combination of paclitaxel with recombinant human granulocyte colony-stimulating factor (rhG-CSF). On the basis of these results, a clinical trial was initiated using rhG-CSF with paclitaxel for PBSC mobilization in high-risk breast cancer patients. The mobilized PBSC were evaluated for CD34(+) cell number, mononuclear cell content, and clonogenic potential. One-hundred and seventeen breast cancer patients received paclitaxel (300 mg/m(2)) administered as a 24-h continuous intravenous infusion. Forty-eight hours after completing paclitaxel, rhG-CSF (5 microg/kg) was initiated and continued until completion of PBSC collection. Leukapheresis was initiated once the white blood cell count reached 1.0 x 10(9)/L. Each collection was evaluated for the numbers of mononuclear cells (MNC) and CD34(+) cells. Clonogenic potential was enumerated using colony-forming units-granulocyte-macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E). Patients receiving paclitaxel with rhG-CSF mobilized a large number of mononuclear cells/apheresis (mean, 3.7 x 10(8); range, 3.3-4.1) and CD34(+) cells/apheresis (mean, 7.2 x 10(6); range, 6.1-8.4). The average number of leukophereses needed was 1.8 (mean, range 1.6-2.0). Colony growth was normal with 178.9 x 10(5) and 214.8 x 10(5) colonies counted in CFU-GM and BFU-E assays, respectively. Patients engrafted platelets and neutrophils on day 10 following transplantation. In conclusion, PBSC mobilization with paclitaxel and rhG-CSF results in a large number of mononuclear cells and CD34(+) cells with normal clonogenic potential. The cells engraft normally following high-dose chemotherapy and autologous stem cell transplantation in high-risk breast cancer patients. These results demonstrate that paclitaxel with rhG-CSF is an efficient mobilizing agent in high-risk breast cancer patients.
Meehan
Kenneth R
KR
Division of Hematology and Oncology, Bone Marrow Transplant Program, Georgetown University Medical Center and the Vincent T. Lombardi Cancer Center, Washington, DC 20007, USA. Kenneth.R.Meehan@hitchcock.org
Slack
Rebecca
R
Gehan
Edmund
E
Herscowitz
Herbert B
HB
Areman
Ellen M
EM
Ebadi
Mark
M
Cairo
Mitchell S
MS
Lippman
Marc E
ME
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D001943:Breast Neoplasms / Q000628:therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007958:Leukocyte Count; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D011379:Prognosis; D011994:Recombinant Proteins
D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel