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 proliferation of myeloid leukemia cells and thereby increase their susceptibility to anti-cancer agents. By in vitro colony assay, the rhG-CSF-responsive 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 killing 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 clone when treated in vitro. Encouraged by these in vitro results, we used rhG-CSF as a component of a conditioning regimen for 15 relapsed AML patients who were receiving allogeneic BMT. The patients were conditioned with total body irradiation (TBI) and high-dose Ara C. rhG-CSF was infused continuously at a dose of 5 micrograms/kg/day from 24 h before the 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 adverse effects. After BMT, four patients died of non-leukemic causes and three patients had leukemic relapse: the other eight patients have remained disease-free for 200-1600 (median 417) days. The actuarial probabilities of relapse and disease-free survival (DFS) at 4.4 years after BMT were 43.2% and 41.7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Takahashi
S
S
Department of Hematology-Oncology, University of Tokyo, Japan.
Okamoto
S I
SI
Shirafuji
N
N
Ikebuchi
K
K
Tani
K
K
Shimane
M
M
Matsudaira
T
T
Irie
S
S
Tsuruta
T
T
Matsuishi
E
E
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006031:Glycosylation; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D008297:Male; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D014407:Tumor Cells, Cultured; D014916:Whole-Body Irradiation
D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor