Monitoring plasma nucleosome concentrations to measure disease response and progression in dogs with hematopoietic malignancies

Background Hematopoietic malignancies are extremely common in pet dogs and represent nearly 30% of the malignancies diagnosed in this population each year. Clinicians commonly use existing tools such as physical exam findings, radiographs, ultrasound and baseline blood work to monitor these patients for treatment response and remission. Circulating biomarkers, such as prostate specific antigen or carcinoembryonic antigen, can be useful tools for monitoring treatment response and remission status in human cancer patients. To date, there has a been a lack of useful circulating biomarkers available to veterinary oncology patients. Methods Circulating plasma nucleosome concentrations were evaluated at diagnosis, throughout treatment and during remission monitoring for 40 dogs with lymphoma, acute myelogenous leukemia and multiple myeloma. Additionally, C-reactive protein and thymidine kinase-1 levels were recorded. Results Plasma nucleosome concentrations were significantly higher at diagnosis and progressive disease than they were when dogs were in remission. All but two dogs had plasma nucleosome concentrations that returned to the low range during treatment. These two dogs had the shortest progression free and overall survival times. Dogs with the highest plasma nucleosome concentrations had a significantly shorter first progression free survival than dogs with lower plasma nucleosome concentrations at diagnosis. Plasma nucleosome concentrations correlated better with disease response and progression than either thymidine kinase or C reactive protein. Conclusions Plasma nucleosome concentrations can be a useful tool for treatment monitoring and disease progression in dogs with hematopoietic malignancies. ### Competing Interest Statement JVT, TK, MH, TB and GM are employees of Belgian Volition, Volition Diagnostics UK ltd & Volition America, which have patents covering Nu. Q technology and are developers of Nu.QTM assays. Volition Veterinary is a joint venture between Belgian Volition and Texas A&M University. HWR is a paid consultant of Volition Veterinary. EW, TM, PM, MM and JJ have no conflicts of interest to declare. Additional salary support for TM was provided by the Fred and Vola Palmer Chair in Comparative Oncology held by HWR. The Palmers did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support for the authors? salaries (T.M.). This does not alter our adherence to PLoS One policies on sharing data and materials.