Heterogeneity of circulating hematopoietic progenitors in cancer patients treated with high-dose cyclophosphamide and recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF).
Antigen CD34+ cells represent 1-4% of adult bone marrow cells comprising virtually all hematopoietic colony-forming progenitors in-vitro and probably also stem cells capable of restoring hematopoiesis of lethally irradiated hosts. We report that sizable numbers of CD34+ cells transiently circulate in the peripheral blood (PB) of patients treated with high-dose (7 g/sqm) cyclophosphamide (HD-CTX) with or without recombinant human glycosylated granulocyte macrophage colony stimulating factor (rhGM-CSF). Evidence is presented demonstrating that CD34+ cells from PB possess qualitatively normal hematopoietic colony growth and high cloning efficiency similarly to marrow CD34+ cells. In addition, CD34+ cells from PB are shown to display heterogeneous flow cytometry characteristics and differentiation antigens analogous to those from bone marrow, i.e., CD34+/CD33-, CD34+/CD13-, CD34+/CD38-, CD34+/CD11b, CD34+/DRlow+ cells have light scatter properties of small lymphocytes while CD34+/CD33+, CD34+/CD13+, CD34+/CD38+, CD34+/CD11b+, CD34+/DRhigh+ cells have light scatter properties of blast-like cells. In HD-CTX treated patients, CD34+ cell circulation is 5-fold enhanced by rhGM-CSF 5.5 micrograms/kg/day by continuous iv infusion for 14 days. During the second-third week after HD-CTX, large-scale collection of PB leukocytes by 3-4 continuous-flow leukaphereses allows the yield of 2.19-2.73 x 10(9) or 0.45-0.56 x 10(9) CD34+ cells, depending on whether or not patients receive rhGM-CSF. The number of CD34+ cells retrieved from PB by leukaphereses exceeds the number that can be harvested by multiple bone marrow aspirations under general anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Siena
S
S
C. Gandini Transplantation Unit, Istituto Nazionale Tumori, Milan, Italy.
Bregni
M
M
Ravagnani
F
F
Brando
B
B
Tarella
C
C
Bonadonna
G
G
Gianni
A M
AM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D003115:Colony-Stimulating Factors / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000188:drug therapy; D011994:Recombinant Proteins / Q000008:administration & dosage
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide