THERAPEUTIC EFFECTS OF DIETHYLCARBAMAZINE AND 3'-AZIDO-3'-DEOXYTHYMIDINE ON FELINE LEUKEMIA-VIRUS LYMPHOMA FORMATION

Twenty-four specific pathogen-free kittens were infected with the Rick ard strain of feline leukemia virus (FeLV(R)). The kittens were divide d into four equal groups and were orally administered either a high do se of diethylcarbamazine (DECH, 12 mg kg(-1)), a low dose of diethylca rbamazine (DECL, 3 mg kg(-1)), 3'-azido-3'-deoxythymidine (AZT, 15 mg kg(-1), b.i.d.), or a placebo (250 mg granular dextrose) daily for 10 weeks, Flood was collected at 2-week intervals for complete blood coun ts (CBC) and flow cytometric analysis (FAGS) of peripheral blood lymph ocytes (PBL). Plasma was assayed for antibodies to FeLV gp70 and for F eLV p27 antigen using ELISA assays, For FAGS analysis, lymphocytes wer e incubated with monoclonal antibodies to feline Pan T, CD8(+), CD4(+) , and B cell (Anti-Ig) antigens. In the placebo treated cats, FeLV(R) infection caused an early (2 weeks p.i.) and persistent decrease in le ukocyte numbers attributable primarily to a decrease in neutrophil num bers and a secondary lesser decrease in B and CD4(+) lymphocyte number s. The DEC-treated groups showed a delayed but similar leukopenia by 4 weeks p.i. The lymphopenia in the DEC groups (primarily B cells and C D4(+) cells) was reversed by 10 weeks p.i., but the neutropenia persis ted, AZT treatment inhibited FeLV,induced lymphopenia but did not prev ent a reduction in neutrophil numbers. A marked p27 antigenemia that p eaked at 4 weeks p.i. was noted in the placebo treated cats and in mos t cats (11/12) treated with either dose of DEC. However, AZT significa ntly inhibited the p27 antigenemia and all cats were negative for p27 antigen between 6 and 10 weeks of treatment. In general, placebo treat ed cats as well as DECH and DECL cats had low levels of antibody to gp 70 throughout the study, suggesting FeLV(R)-induced immunosuppression, In contrast, significantly higher titers of anti-gp70 antibodies were seen in AZT-treated cats at 6 weeks p.i., and were maintained through out treatment. Eighteen month survival rates provide efficacy data for AZT as well as both DEC treatment groups. While all placebo treated c ats were euthanized by 52 weeks p.i. due to FeLV associated lymphomas with a mean survival time of 35.5 weeks p.i., median survival time of the AZT treated group was greater than or equal to 102 weeks p.i., whi le that of the DECH and DECL groups was 69.7 and 72 weeks p.i., respec tively. Thus, DEC as well as AZT therapy delays the development of lym phomas associated with FeLV infection and significantly improves survi val.