Differential effect of the combination methotrexate/(dl)-5-methyltetrahydrofolate on lymphoid malignant and normal bone marrow cells.
It has been reported that high doses of (dl)-5-methyltetrahydrofolate (mTHF) inhibit the growth of leukemic cell lines. We studied the effect of methotrexate (MTX) and mTHF in combination on the lymphoid cell lines BALM 3, CEM, MOLT 4 and P3HR1 by evaluating the clonogenic cell reduction in a limiting dilution assay. Cells were treated with 0.1 mM MTX for 4 h and 1 mM mTHF for 48 h. The growth of the cell lines was inhibited by 1 mM mTHF, with a clonogenic cell reduction of 3.5 log. MTX, following by mTHF after a delay of 8-24 h, caused a substantial killing of lymphoid leukemia cells, greater than the effect of either drug alone. The clonogenic cell reduction caused by the combination MTX-mTHF ranged from about 3.5 to 4.5 log, depending on the cell line studied. Normal hemopoiesis, as evaluated by primitive hematopoietic precursor colonies and granulocyte-macrophage colony-forming units (CFU-GM) was only slightly affected by the MTX-mTHF treatment at a dose and schedule which caused up to 4.5 log reduction of the leukemic cell lines. mTHF-MTX treatment could be useful in vitro for purging bone marrow cells in autologous bone marrow transplantation for acute leukemia.
Bernabei
P A
PA
Department of Hematology USL 10/D, Florence, Italy.
Bensinger
W I
WI
D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy*; D015458:Leukemia, T-Cell / Q000188:drug therapy*; D008727:Methotrexate / Q000494:pharmacology*; D013763:Tetrahydrofolates / Q000494:pharmacology*; D013997:Time Factors; D014410:Tumor Stem Cell Assay
D013763:Tetrahydrofolates; C005984:5-methyltetrahydrofolate; D008727:Methotrexate