Transplantation potential of hematopoietic cells released into the circulation during routine chemotherapy for non-Hodgkin's lymphoma.
Primitive hematopoietic cells released into the peripheral blood (PB) were studied in 50 patients with high-grade non-Hodgkin's lymphoma enrolled in a phase III trial of intensive weekly chemotherapy (VAPEC-B) alone or with granulocyte colony-stimulating factor (G-CSF). Mononuclear cells numbers were monitored and their in vitro growth potential assessed in clonogenic progenitor cell assays and in long-term culture. Total colony-forming cells (granulocyte-macrophage [GM], burst-forming unit, erythroid [BFU-E], Mix-CFC) were increased 40-fold (median) over baseline with chemotherapy alone and 106-fold with chemotherapy and G-CSF after the final dose. CD34+ cells were increased to a median of 4%, equivalent to that in normal bone marrow (BM) controls. Circulating colony-forming cell levels were maximal when the recovering total white blood cell (WBC) count reached 5 to 10 x 10(9)/L. The timing of the maximum was reproducible in individual patients. Therefore the WBC count can be used as a guide to the timing of leukapheresis. PB cells from normal controls' and patients' prechemotherapy were unable to sustain hemopoiesis in two-stage long-term cultures. In contrast, PB cells collected from patients primed with chemotherapy alone or chemotherapy with G-CSF at the time of predicted maximal colony-forming cell release were able to generate and sustain hematopoiesis in long-term cultures at a level comparable or superior to normal BM. These findings indicate that the use of G-CSF after routine outpatient chemotherapy stimulates maximal release of primitive hemopoietic cells into the circulation, including colony-forming cells and long-term culture-initiating cells. Their numbers are comparable with those in normal BM and are such that a single leukapheresis will usually yield enough cells for hemopoietic reconstitution after myeloablative chemotherapy.
Pettengell
R
R
Department of Experimental Haematology, Paterson Institute for Cancer Research and Christie Hospital, Manchester, UK.
Testa
N G
NG
Swindell
R
R
Crowther
D
D
Dexter
T M
TM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D009000:Monocytes / Q000473:pathology / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage
D011994:Recombinant Proteins; D001761:Bleomycin; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide