Experimental hematology
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Experimental hematology · Oct 1996
Granulocyte-macrophage colony-stimulating factor (GM-CSF) priming of high-dose etoposide and cyclophosphamide: a pilot trial.
Given the limitations of bone marrow transplantation (BMT), alternative approaches to deliver dose-intensive regimens without stem cell support are needed. Administration of hematopoietic growth factors before high-dose chemotherapy (priming) may reduce myelosuppression directly, delaying the onset of neutropenia by expanding the mature neutrophil compartment, and shortening the duration of neutropenia by expanding progenitor cell mass. Priming may also render progenitor populations mitotically quiescent after growth factors are withdrawn, thereby making them less sensitive to the cytotoxic effects of chemotherapy. ⋯ Furthermore, much of the leukocyte expansion was caused by an increase in eosinophils, which would not be expected to accelerate hematopoietic recovery. GM-CSF priming did not appear to have a significant impact on hematopoietic recovery after high-dose etoposide and cyclophosphamide, as there was no significant difference in 1) recovery to an ANC > 500/microL compared to a historical control group that received no growth factor (median of 29 and 30 days, respectively; p = 0.4), 2) number of days with an ANC < 500/microL (median of 19 and 20 days, respectively; p = 0.11), and 3) number of days to an untransfused platelet count > or = 50,000/microL (median 36 and 32 days, respectively; p = 0.23). The failure of GM-CSF priming may be a result of its modest stimulation of hematopoiesis or the expansion of a committed progenitor cell population that is exquisitely sensitive to this regimen.
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Experimental hematology · Oct 1996
Improved survival of lethally irradiated recipient mice transplanted with circulating progenitor cells mobilized by IL-8 after pretreatment with stem cell factor.
We have demonstrated previously that a single bolus-injection of interleukin (IL)-8 induces instant mobilization of hematopoietic progenitor cells (HPC) in mice and primates. To further improve the mobilization of HPC, we treated mice with hematopoietic growth factors (HGF) before IL-8-administration. The mobilized HPC were transplanted into lethally irradiated recipient mice to study the effects on survival. ⋯ Transplantation of 1.5 x 10(5) MNC obtained from donors pretreated with SCF for 2 days prior to IL-8 mobilization resulted in a significantly enhanced survival of 100% of the recipients, whereas recipients of PBM-NCs derived from donors treated with SCF only or IL-8 as a single injection had a survival rate at day 60 of only 50% and 60% respectively. When equal numbers of IL-8 mobilized MNCs from G-CSF, GM-CSF, or IL-3 pretreated donors were transplanted into lethally irradiated recipients, no such survival-advantage was observed. We conclude that pretreatment with SCF for 2 days improves the mobilizing effect induced by IL-8 and that transplantation of these cells enhances survival of lethally irradiated recipients.