Mobilization of peripheral blood progenitor cells by sequential administration of interleukin-3 and granulocyte-macrophage colony-stimulating factor following polychemotherapy with etoposide, ifosfamide, and cisplatin.
We report on the requirements that have to be met to combine a standard-dose chemotherapy regimen with broad antitumor activity with the mobilization of peripheral blood hematopoietic progenitor cells. Thirty-two cancer patients were given a 1-day course of chemotherapy consisting of etoposide (VP16), ifosfamide, and cisplatin (VIP; n = 46 cycles), followed by the combined sequential administration of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Control patients received GM-CSF alone or were treated without cytokines. Maximum numbers of peripheral blood progenitor cells (PBPC) were recruited on day 13 to 17 after chemotherapy, with a median of 418 CD34+ cells/microL blood (range, 106 to 1,841) in IL-3/GM-CSF-treated patients, 426 CD34+/microL (range, 191 to 1,380) in GM-CSF-treated patients, and 46 CD34+/microL (range, 15 to 148) in patients treated without cytokines. In parallel, there was an increase in myeloid (10,490 colony-forming unit-granulocyte-macrophage [CFU-GM]/mL blood; range, 1,000 to 23,400), as well as erythroid (10,660 burst-forming unit-erythroid [BFU-E]/mL blood; range, 3,870 to 24,300) and multipotential (840 CFU-granulocyte, erythrocyte, monocyte, megakaryocyte [GEMM]/mL blood; range, 160 to 2,070) progenitor cells in IL-3 plus GM-CSF-treated patients. In GM-CSF-treated patients, significantly less precursor cells of all lineages were mobilized, particularly multipotential progenitors (400 CFU-GEMM/mL blood; range, 200 to 2,150). Only small numbers of CD34+ cells and clonogenic progenitor cells could be recruited in intensively pretreated patients. Our data document that after standard-dose chemotherapy-induced bone marrow hypoplasia, IL-3 plus GM-CSF can be used to recruit PBPC, which might shorten the hematopoietic recovery after high-dose chemotherapy in chemosensitive lymphomas or solid tumors.
Albert-Ludwigs-University Medical Center, Department of Medicine I, Freiburg, Germany.
W
W
Brugger
K
K
Bross
J
J
Frisch
P
P
Dern
B
B
Weber
R
R
Mertelsmann
L
L
Kanz
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols; D002452:Cell Count; D002945:Cisplatin / Q000627:therapeutic use; D004912:Erythrocytes / Q000473:pathology; D015672:Erythroid Precursor Cells / Q000473:pathology; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006098:Granulocytes / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D016130:Immunophenotyping; D007377:Interleukin-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008533:Megakaryocytes / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*
D015703:Antigens, CD; D018952:Antigens, CD34; D007377:Interleukin-3; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin; D007069:Ifosfamide