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

Abstract

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.