EFFECT OF INTERLEUKIN-3 PRETREATMENT ON GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-INDUCED MOBILIZATION OF CIRCULATING HEMATOPOIETIC PROGENITOR CELLS

Recombinant human colony stimulating factors (CSFs) as single agents are increasingly used for mobilizing peripheral blood progenitor cells (PBPCs) for stem cell transplantation. We have shown in rhesus monkeys that interleukin-3 (IL-3) pretreatment markedly potentiated the increase in PBPC numbers of subsequent administration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the effect of IL-3 pretreatment on GM-CSF-induced mobilization of PB progenitors in patients who were potential candidates for autologous stem cell transplantation (n=16). Patients were treated with GM-CSF at a dose of 5 mu g/kg/d for 5 d and after a treatment free interval received another cycle of G11 I-CSF immediately following pretreatment with IL-3 at different doses and duration: 2.5 mu g/kg/d (n=4), 5 mu g/kg/d (n=3) and 10 mu g/kg/d (n=3) for 3d, 5 mu g/kg/d for 7d (n=4) and 5 mu g/kg/d for 14d (n=2), respectively. Only 7d pretreatment with IL-3 showed consistent effects. Although IL-3 did not mobilize by itself, pretreatment with 5 mu g/kg/d of IL-3 for 7d significantly potentiated GM-CSF-induced mobilization of PB CFU-GM numbers, leading to a mean increase in PB CFU-GM numbers over baseline by 18.5 + 5.2 (SEM) fold by IL-3/GM-CSF as compared to a 4.7 +/- 1.7-fold increase by GM-CSP alone. A significant enhancement by the 7 d IL-3 pretreatment was also observed for erythroid (BFU-E) and multipotential progenitor cells (CFU-mix) which were 3.3+/-1.3 and 3.4+/-0.9-fold, respectively, mobilized by GM-CSF alone, as compared to 8.5 +/- 2.3- and 19.2 +/- 3.4-fold, respectively, by the IL-3/GM-CSF combination. Our results suggest that 7 d pretreatment with IL-3 may be a useful mean to augment mobilization of circulating progenitors by more lineage-restricted CSFs. These findings may be important for the design of mobilization strategies that use growth factors without preceding chemotherapy.