MALCOLM S. MITCHELL, M.D.; MACLYN E. WADE, M.D.; RONALD C. DECONTI, M.D.; JOSEPH R. BERTINO, M.D.; PAUL CALABRESI, M.D., F.A.C.P.
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.
MITCHELL MS, WADE ME, DECONTI RC, BERTINO JR, CALABRESI P. Immunosuppressive Effects of Cytosine Arabinoside and Methotrexate in Man. Ann Intern Med. ;70:535–546. doi: 10.7326/0003-4819-70-3-535
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Published: Ann Intern Med. 1969;70(3):535-546.
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