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 [see comments]

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.

The Role of Cytokines and Adhesion Molecules for Mobilization of Peripheral Blood Stem Cells

“…In addition to G-CSF and GM-CSF, other cytokines such as interleukin 3 (IL-3), IL-8, IL-11, stem cell factor (SCF), flt-3 ligand, or macrophage inflammatory protein-1α (MIP-1α) might be used for mobilization of CD34 + cells [29][30][31][32][33][34][35][36]. The ability of these cytokines to mobilize PBSC when given as single agents is apparently not better than that of G-CSF or GM-CSF.…”

Timing of the appearance of multipotential and committed haemopoietic progenitors in peripheral blood after mobilization in patients with lymphoma

“…This consideration is likely to apply to measurement of expression by circulating cells of CD34 antigen, most commonly used as a guide for the optimal timing of stem cell collections (To 1994). For this purpose, the CD34 + fraction can be measured quickly enough to guide the timing of stem cell harvest, but it is known to be a heterogeneous population with only a minority of cells possessing the properties of self-renewal and differentiation (Bernstein, Andrews & Zsebo, 1991;Brugger et al, 1992). Nevertheless, the present study indicates that strategies for PBSC harvests based on peak values for total progenitor cell numbers are also likely to capture the maximum number of multipotential progenitors.…”

Population Pharmacokinetic and Pharmacodynamic Modeling of LY2510924 in Patients With Advanced Cancer

“…26,27 Similarly, a combination of etoposide, ifosfamide, and cisplatin was shown to promote a small mobilization of CD341 cells in cancer patients. 28 Thus, attempts were made to model the influence of the SoC therapy, EPO, and/or G-CSF on the CD341 cell production rate or mobilization rate using a time-varying covariate approach (in which the presence of comedication was associated with a proportional shift in the base rate) or using the dosing history in a KPD modeling approach. 18 These effects operated in both Study CXAC arms.…”