Comparison of biological activity and safety of recombinant canine erythropoietin with that of recombinant human erythropoietin in clinically normal dogs

Objective-To determine whether recombinant canine erythropoietin (rcEPO) st imulates erythropoiesis in dogs without causing the immunogenicity problem (ie, erythroid hypoplasia) associated with recombinant human erythropoietin (rhEPO). Animals-13 clinically normal dogs. Procedure-Dogs were randomly assigned to 2 groups; 1 group (n = 6) received rhEPO, whereas the other group (7) received rcEPO. Both groups received SC injections of diluent for 4 weeks before initialing treatment with erythro poietin (100 U/kg of body weight, SC, 3 times/wk), Hematocrit and absolute reticulocyte count were monitored weekly, CBC were done monthly, and bone m arrow aspirates for cytologic evaluation were obtained before and at 4, 8, 16, and 24 weeks during treatment, Results-Weekly mean Her and absolute reticulocyte count increased in both g roups of dogs during the first 2 weeks of treatment. For dogs receiving rhE PO, precipitous decreases in reticulocyte number and more gradual decreases in Hct were associated with development of erythroid hypoplasia. Dogs rece iving rhEPO developed erythroid hypoplasia by week 4 (n = 4), 8 (1), or 16 (1), With cessation of rhEPO treatment after diagnosis of erythroid hypopla sia, RBC production recovered 5 to ii weeks (median, 7 weeks) later, In con trast, rcEPO treatment caused sustained increases in Hct and reticulocytosi s. None of the dogs receiving rcEPO developed erythroid hypoplasia. Conclusions-rcEPO stimulated erythrocyte production in clinically normal do gs during a 24-week period without causing the erythroid hypoplasia encount ered in rhEPO-treated dogs. Clinical Relevance-Because rcEPO did not cause erythroid hypoplasia, rcEPO may represent an improved option, compared with rhEPO, for treatment of ery thropoietin-dependent anemia in dogs.