POTENTIATION OF GRANULOCYTE-COLONY-STIMULATING FACTOR-INDUCED MOBILIZATION OF CIRCULATING PROGENITOR CELLS BY 7-DAY PRETREATMENT WITH INTERLEUKIN-3

Granulocyte colony-stimulating factor (G-CSF) as a single agent is inc reasingly used for the mobilization of peripheral blood progenitor cel ls (PBPCs) for stem cell tranplantation. In patients with perturbed he matopoiesis the mobilizing capacity of G-CSF alone may be inadequate. We have shown in rhesus monkeys that interleukin-3 (IL-3) pretreatment markedly potentiated the increase in PBPC numbers by subsequent admin istration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the effect of IL-3 pretreatment on G-CSF-induced mobilization of PBPCs in 6 patients with Hodgkin's disease (n = 5) or non-Hodgkin's lymphoma (n = 1) who had low progenitor cell numbers because of previous chemothe rapy. Patients were treated in cycle 1 with G-CSF at a dose of 5 mu g/ kg/d for 5 days and, after a treatment-free interval, received cycle 2 consisting of 5 mu g/kg/d of IL-3 for 7 days followed by G-CSF again at a dose of 5 mu g/kg/d for 5 days. G-CSF alone increased the the mea n number of circulating colony-forming units-GM (CFU-GM) by 21-fold, t he number of burst-forming units-erythroid (BFU-E) by 9-fold, and the number of CFU-mix by 24-fold over pretreatment values. Treatment with 5 mu g/kg/d of IL-3 for 7 days did not mobilize by itself but signific antly potentiated G-CSF-induced mobilization of all progenitor cell ty pes leading to a 56-, 15-, and 46-fold increase over baseline of CFU-G M, BFU-E, and CPU-mix numbers, respectively. In 2 patients in whom leu kapheresis was performed after G-CSF alone the target number of 2 x 10 (6)/kg CD34(+) cells was not reached. However, leukapheresis after the IL-3/G-CSF combination obtained greater than or equal to 2 x 10(6)/kg CD34(+) cells in 3 of 6 patients, including both patients who had ina dequate collection after G-CSF alone. In one patient adequate function of mobilized progenitors could be shown by the demonstration of rapid trilineage engraftment after infusion of progenitors after myeloablat ive chemotherapy. Seven-day pretreatment with IL-3 may be a useful mea n to augment mobilization of circulating progenitors by G-CSF. The com bination of IL-3 and G-CSF seems to allow the procurement of sufficien t numbers of PBPCs in some patients who cannot be mobilized adequately by G-CSF alone. (C) 1996 by The American Society of Hematology.