Primitive multilineage progenitor cells predominate in peripheral blood early after mobilization with high-dose cyclophosphamide and GM-CSF or G-CSF.
The change in phenotype, number and proliferative capacity of peripheral blood hematopoietic progenitors (PBHP) was studied in six patients with multiple myeloma during hematopoietic recovery after mobilization with high-dose cyclophosphamide and GM-CSF or G-CSF. In all six patients the first CD34+ cells appearing in the peripheral blood (PB) after cytoreductive treatment were predominantly CD34+/33- (> 70%). At later stages when leukapheresis procedures were started, the CD34+/33+ cells predominated in five of six patients. In leukapheresis harvests of peripheral blood, and in bone marrow addition of SCF and IL-6 to the culturing medium enhanced the plating efficiency. In peripheral blood an increase from 12 to 22% for CD34+/33+ and from 6 to 14% for CD34+/33- was observed. In normal bone marrow we observed an increase from 15 to 23% for CD34+/33+ and from 7 to 17% for CD34+/33-. Highly proliferative progenitors (>500 cells) in the CD34+/33- fraction appeared to be dependent on the addition of 'stem cell recruiting factors' (SCF and IL-6); in bone marrow the percentage of wells with >500 cells increased from 0.9 to 12.6% after SCF+IL-6 and in PBHP from 2 to 9%. We conclude that the first progenitors appearing in the peripheral blood after priming with high-dose cyclophosphamide and GM- or G-CSF have a more primitive immunophenotype, CD34+/33-.
Croockewit
S
S
Division of Hematology, University Hospital Nijmegen, The Netherlands.
Raymakers
R
R
Trilsbeek
C
C
Dolstra
H
H
Pennings
A
A
de Witte
T
T
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000494:pharmacology; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy / Q000628:therapy; D063268:Sialic Acid Binding Ig-like Lectin 3; D019089:Stem Cell Factor
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D016298:Hematopoietic Cell Growth Factors; D015850:Interleukin-6; D063268:Sialic Acid Binding Ig-like Lectin 3; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide