Assessment of temporal association of relapse of canine multicentric lymphoma with components of the CHOP protocol: Is cyclophosphamide the weakest link?

•Dogs with lymphoma relapsed significantly more frequently when cyclophosphamide was used as an induction agent.•New chemotherapy protocols which replace cyclophosphamide with other agent/s might improve outcomes.•The cumulative or synergistic effects of previously used drugs did not affect treatment.•Relatively higher dose rates in small dogs may produce better responses and longer remission times. Combination chemotherapy, using cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), is the most commonly used treatment for canine lymphoma. Most affected dogs respond during the initial stages of chemotherapy, but many relapse. The aim of this study was to evaluate the relationship between the use of specific chemotherapy drugs and clinical relapse, using the modified Madison-Wisconsin, 25 week chemotherapy protocol. Forty-one of 68 dogs affected with multicentric lymphoma relapsed during the treatment period. Relapse occurred more frequently after the administration of cyclophosphamide (n = 24; P