Ex vivo expanded peripheral blood progenitor cells provide rapid neutrophil recovery after high-dose chemotherapy in patients with breast cancer

• Published in: Blood Vol. 96; no. 9; pp. 3001 - 3007
• Main Authors: McNiece, Ian, Jones, Roy, Bearman, Scott I., Cagnoni, Pablo, Nieto, Yago, Franklin, Wilbur, Ryder, John, Steele, Andrea, Stoltz, Judy, Russell, Peggy, McDermitt, Janet, Hogan, Christopher, Murphy, James, Shpall, Elizabeth J.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-11-2000; The Americain Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens, CD - blood; Antigens, CD34 - blood; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cell Culture Techniques - methods; Cell Division; Cells, Cultured; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor - therapeutic use; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - pathology; Humans; Leukocyte Count; Medical sciences; Neoplasm Staging; Neutrophils - physiology; Polyethylene Glycols - therapeutic use; Recombinant Proteins - therapeutic use; Regression Analysis; Stem Cell Factor - therapeutic use; Thrombopoietin - therapeutic use; Time Factors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Antineoplastic agent; Human; Cell culture; Leukopenia; Stem cell; Granulocyte; Hematopoietic cell; Hemopathy; Malignant tumor; Prevention; Mammary gland diseases; Autograft; Chemotherapy; Treatment; Ex vivo; Engraftment; Graft; Myelosuppression; Mammary gland; Neutrophil; Neutropenia
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.9.3001

Ex vivo expanded peripheral blood progenitor cells (PBPCs) have been proposed as a source of hematopoietic support to decrease or eliminate the period of neutropenia after high-dose chemotherapy. CD34 cells were selected from rhG-CSF mobilized PBPCs from patients with breast cancer and were cultured for 10 days in defined media containing 100 ng/mL each of rhSCF, rhG-CSF, and PEG-rhMGDF in 1 L Teflon bags at 20 000 cells/mL. After culture the cells were washed and reinfused on day 0 of transplantation. On day +1, cohort 1 patients (n = 10) also received an unexpanded CD34-selected PBPC product. These patients engrafted neutrophils (absolute neutrophil count, >500/μL) in a median of 6 (range, 5-14) days. Cohort 2 patients (n = 11), who received expanded PBPCs only, engrafted neutrophils in a median of 8 (range, 4-16) days. In comparison, the median time to neutrophil engraftment in a historical control group of patients (n = 100) was 9 days (range, 7-30 days). All surviving patients are now past the 15-month posttransplantation stage with no evidence of late graft failure. The total number of nucleated cells harvested after expansion culture was shown to be the best predictor of time to neutrophil engraftment, with all patients receiving more than 4 × 107 cells/kg, engrafting neutrophils by day 8. No significant effect on platelet recovery was observed in any patient. These data demonstrate that PBPCs expanded under the conditions defined can shorten the time to engraftment of neutrophils compared with historical controls and that the rate of engraftment is related to the dose of expanded cells transplanted.