AKCCHF grant #01494-A (closed)

Identifying the cause of drug resistance in canine lymphoma.

Bonnie L Boudreaux, DVM, Louisiana State University [$1000 from AKCCHF donor advised fund]

Abstract from AKCCHF.org website:

“Development of multidrug resistance is a major obstacle in the adequate treatment of both human and veterinary cancer patients with chemotherapy. Development of resistance has been linked to the expression of a protein, P-glycoprotein (P-gp). Increased levels of P-gp expression have been documented in patients at the time of tumor relapse and are thought to be a primary reason for chemotherapeutic failure.

The goal of this study is to compare the level of P-gp expression in lymphocytes found in different lymph nodes and peripheral blood in lymphoma patients using flow cytometry. Dr. Boudreaux believes that lymphocyte expression in the peripheral blood will directly correlate with that in lymph node lymphocytes and that there will not be variation amongst the lymph nodes in a given patient. Additional objectives would be to follow fifty canine lymphoma patients throughout their chemotherapy protocols to evaluate the changes in the level of P-gp expression over time in blood lymphocytes and at relapse to determine if there is a threshold of P-gp expression that develops prior to an individual relapsing.

If their hypothesis is accurate, the chemotherapeutic management of patients could be drastically altered, with significant emphasis put on levels of P-gp expression as a clinically relevant prognostic factor. Additional information regarding the level of P-gp expression relative to individual patient demographics will be analyzed for significance.”

Completed Project Summary from AKCCHF.org website:

This study was being conducted at the Louisiana State University School of Veterinary Medicine. Unfortunately we were only able to enroll 9 cases to date. Additionally, many of the dogs enrolled have not progressed with their cancer in a normal fashion. However, after analysis of the data to date, we have found that the levels of p-glycoprotein in blood lymphocytes throughout the chemotherapy protocol are not reflective of remission status or response to therapy. In fact, there is quite a high degree of variability in the samples obtained. However, many of the dogs also had high levels at the start of the protocol (at diagnosis). Additionally, we have had only two dogs finish the entire CHOP protocol. This has made drawing any further conclusions very difficult. However, the one dog that has had the longest survival and is still alive at over 18 months had much lower values of P-glycoprotein at diagnosis than the other dogs. There is reason to support that the levels of p-glycoprotein at the time of diagnosis could be reflective of long term survival in patients undergoing a CHOP based protocol for lymphoma. An abstract presented at ACVIM in 2002 found that functional assays of p-gp may provide useful information in dogs with lymphoma. Currently, there are no papers evaluating the levels of p-glycoprotein at the time of diagnosis in lymphoma patients. Although, it is only one dog, we feel that a study evaluating the levels of p-glycoprotein at the time of diagnosis by flow cytometry may be beneficial in predicting long term survivors of lymphoma.