RECOMBINANT HUMAN GLYCOSYLATED GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF)-COMBINED REGIMEN FOR ALLOGENEIC BONE-MARROW TRANSPLANTATION IN REFRACTORY ACUTE MYELOID-LEUKEMIA

Recombinant human glycosylated G-CSF (rhG-CSF) may stimulate prolifera tion of myeloid leukemia cells and thereby increase their susceptibili ty to anti-cancer agents. By in vitro colony assay, the rhG-CSF-respon sive NFS-60 leukemic cell clones are more effectively killed by Ara C in the presence of rhG-CSF than in the absence of rhG-CSF, while the k illing of the rhG-CSF-unresponsive HL-60 cell clones is unaffected by rhG-CSF. Leukemia cell colony forming units (L-CFU) derived from most AML patients demonstrate similar results to those of the NFS-60 cell c lone when treated in vitro. Encouraged by these in vitro results, we u sed rhG-CSF as a component of a conditioning regimen for 15 relapsed A ML patients who were receiving allogeneic BMT. The patients were condi tioned with total body irradiation (TBI) and high-dose Ara C. rhG-CSF was infused continuously at a dose of 5 mu g/kg/day from 24 h before t he beginning of TBI to the end of Ara C therapy. Proliferation of the leukemia cells in vivo in response to rhG-CSF was confirmed in 7 of 14 patients tested and the combined use of rhG-CSF had no additional adv erse effects. After BMT, four patients died of non-leukemic causes and three patients had leukemic relapse: the other eight patients have re mained disease-free for 200-1600 (median 417) days. The actuarial prob abilities of relapse and disease-free survival (DFS) at 4.4 years afte r BMT were 43.2% and 41.7%, respectively. These results suggest that t he rhG-CSF-combined preparative regimen for BMT has potential benefit in prolonging the duration of remission after BMT and improving DFS ra te in AML.