Elimination of clonogenic Burkitt's lymphoma cells from human bone marrow using 4-hydroperoxycyclophosphamide in combination with monoclonal antibodies and complement.
One requirement for autologous bone marrow transplantation is the selective removal of malignant cells from normal marrow precursors. Development of a clonogenic assay that detects elimination of up to 5 logs of Burkitt's lymphoma cells in the presence of a 20-fold excess of human bone marrow has permitted the evaluation of two different methods for the selective removal of malignant cells. Treatment with 4-hydroperoxycyclophosphamide (4-HC) (60 to 100 micrograms/mL) eliminated 2.0 to 3.5 logs of clonogenic cells. Antitumor activity depended upon the concentration of 4-HC and the length of incubation, but not upon the concentration of normal bone marrow cells. Comparable removal of clonogenic Burkitt's cells was achieved by treatment with rabbit complement (C') and a combination of J5 anti-common acute lymphoblastic leukemia antigen (J5 anti-CALLA), J2 anti-gp 26, and the B1 anti-B1 murine monoclonal antibodies. A combination of 4-HC and monoclonal antibodies proved slightly but significantly more effective than either single agent in eliminating clonogenic tumor cells. Although treatment with 4-HC markedly reduced granulocyte-macrophage colony-forming units-C (GM-CFU-C) content of human bone marrow, neither treatment with 4-HC nor treatment with monoclonal antibodies and C' eliminated precursor cells that could generate new GM-CFU-C after growth in continuous bone marrow cultures. Our data suggest that treatment with 4-HC in combination with multiple monoclonal antibody reagents could be a safe and effective method of eliminating clonogenic tumor cells from human bone marrow.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D001853:Bone Marrow / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000473:pathology*; D002999:Clone Cells; D003165:Complement System Proteins / Q000276:immunology*; D046508:Culture Techniques; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans
D000911:Antibodies, Monoclonal; D003520:Cyclophosphamide; D003165:Complement System Proteins; C011272:perfosfamide