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)
C. Gandini Transplantation Unit, Istituto Nazionale Tumori, Milan, Italy.
S
S
Siena
M
M
Bregni
F
F
Ravagnani
B
B
Brando
C
C
Tarella
G
G
Bonadonna
A M
AM
Gianni
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