Immunosuppressive Effects of Cytosine Arabinoside and Methotrexate in Man

SUMMARY

Thirty-six patients with nonlymphoid solid tumors who were undergoing therapy with cytosine arabinoside (ara-C) or methotrexate (MTX) were immunized with Escherichia coli Vi antigen and tetanus toxoid to test the primary and secondary immune responses. Ara-C was given as 2 mg/kg body weight intravenous injections for 5 days, or as 10 mg/kg body weight infusions every 4 days for three doses. MTX was administered as infusions of 240 mg/m² body surface area, every 4 days, followed each time by citrovorum factor (Leucovorin®) for as many as 11 consecutive infusions. These relatively nontoxic schedules of ara-C injections and MTX infusions suppressed primary and anamnestic antibody synthesis during therapy. An antibody response occurred in 40% of the patients without further injection of antigen approximately 2 weeks after cessation of therapy. In a delayed primary response only IgM antibody was produced. Ara-C infusions completely inhibited the primary and secondary response during the 4-week period studied but were accompanied by leukopenia. It is postulated that these antimetabolites did not interfere with the recognition of antigen but rather killed a proportion of proliferating lymphocytes. After cessation of therapy, remaining lymphocytes may have multiplied, producing normal titers of serum antibody, although the normal sequence of globulin formation was prevented.