Ex-vivo expansion of bone marrow progenitor cells for hematopoietic reconstitution following high-dose chemotherapy for breast cancer.
The use of hematopoietic growth factors, stromal monolayers, and frequent medium exchange allows the expansion of hematopoietic progenitors ex-vivo. We evaluated the use of ex-vivo expanded progenitor cells for hematopoietic reconstitution following high dose chemotherapy (HDC) in breast cancer patients. Patients with high-risk Stage II or metastatic breast carcinoma underwent bone marrow aspirations using general anesthesia. A total of 675-1125 x 10(6) mononuclear cells (MNC) were seeded for ex-vivo expansion for 12 days in controlled perfusion bioreactors (Aastrom Biosciences, Inc.). The bone marrow cultures, which included the stromal cells collected with the aspirate, were supplemented with erythropoietin, granulocyte-macrophage-colony stimulating factor (GM-CSF)/IL-3 fusion protein (PIXY 321), and flt3 ligand. Stem cell transplant was performed with expanded cells after HDC. A median bone marrow volume of 52.9 mL (range 42-187 mL) was needed to inoculate the bioreactors. Median fold expansion of nucleated cells (NC) and colony forming unit granulocyte-macrophage (CFU-GM) was 4.9 and 9.5, respectively. The median fold expansion of CD34+lin- and long-term culture-initiating culture (LTC-IC) was 0.42 and 0.32, respectively. Five patients were transplanted with ex-vivo expanded NC. Median days to an absolute neutrophil count > 500/microL was 18 (range 15-22). Median days to a platelet count > 20,000/microl was 23 (range 19-39). All patients had sustained engraftment of both neutrophils and platelets. Immune reconstitution was similar to that seen after HDC and conventional stem cell transplantation. We conclude that ex-vivo expansion of progenitor cells from perfusion cultures of small volume bone marrow aspirates, allows hematopoietic reconstitution after HDC.
Bachier
C R
CR
South Texas Cancer Institute, San Antonio 77229, USA. cbachier@txdirect.net
Gokmen
E
E
Teale
J
J
Lanzkron
S
S
Childs
C
C
Franklin
W
W
Shpall
E
E
Douville
J
J
Weber
S
S
Muller
T
T
Armstrong
D
D
LeMaistre
C F
CF
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001835:Body Weight; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy*; D002455:Cell Division / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008875:Middle Aged; D012008:Recurrence; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents