Saturday, 21 April 2012

Going to the dogs … for a new model organism of non-Hodgkin lymphoma


On Tuesday, April 17th, there were two speakers at the One Health Session. The speakers had met each other several years ago through a common veterinary friend. After they discussed their research over lunch for about a year, they started collaborating in research regarding stem cell transplantation in B- and T-cell lymphoma. Steven Suter, VMD, MS, PhD, DACVIM (Oncology) is an Assistant Professor of Oncology in the Department of Clinical Science at NCSU Veterinary Health Complex. He is a veterinary oncologist and the Medical Director of the world’s only Canine Bone Marrow Transplant Unit. Kristy Richards, MD, PhD is an assistant professor in the Department of Genetics and Department of Medicine, Division of Hematology/Oncology at the UNC School of Medicine. Kristy Richards is a medical oncologist; she treats patients with a variety of blood cancers in the Lineberger Cancer Center and her laboratory in IPIT focuses on finding new and better ways to treat lymphoma.

Steve Suter described his bone marrow transplantation (BMT) program in dogs. They have treated 67 dogs since the opening in October 2008 and people are coming from all different states. Lymphoma occurs in a lot of otherwise healthy dogs that are only 3-4 years old. The 2-year survival with the lowest radiation dose has been 33% so far and they expect even better survival rates with the higher doses being used currently. BMT is an alternative to chemotherapy, which has a cure rate of 0%. The costs are lower and the treatment regime is shorter than in humans. The description of the BMT program in dogs was really interesting and it’s not surprising that it’s similar to the human program.

Dr. Suter (standing) discusses starting the only canine bone marrow transplant unit in the world.

The reason for this is that >95% of all human BMT protocols were first perfected in dogs. Dogs are a better model than mice, not only because of their size, but also because of the natural occurrence of lymphoma in dogs. To test new medications, we do not need to develop an animal model in which we first make the dogs sick, we can use the dogs that develop lymphoma spontaneously. This way both science and the dogs/owners are helped. My own concern, the quality of life of these dogs, seems to be well monitored. After this session, I believe that the dogs do not suffer a lot from the treatment and that they recover well. In the case of incurable disease, euthanasia remains an option, just like dogs that do not participate in clinical trials.

Kristy Richards mainly told us about her research. She explained to us why dogs are more than an animal model to her. By combining the findings of genetic studies in humans, dogs, and mice, she has been able to generate hypotheses that she could never have made if she studied only one or two of the species. B-cell lymphomas are more common in both humans and dogs and have a better outcome than T-cell lymphoma. She explained to us how research in humans has discovered GCB- and ABC- subtypes that have different responses to treatment in research settings. She tried to duplicate these results, but so far has not been able to do this conclusively in humans or dogs. However, Dr. Richards did find another subtype, IGHV, which might correlate better with clinical outcomes.

Dr. Richards explains how including dogs, mice, and humans in research can yield more information than any two alone.

During the last minutes, both speakers shared their thoughts about funding opportunities for their type of research: translational research that is carried out in animal-patients, instead of animal models. Most of their funding is coming from medical research societies at the moment. They are also exploring possible collaborations with pharmaceutical companies, to test efficacy and pharmacokinetic properties of new drugs in the treatment of lymphoma.

Post authored by Margreet Harskamp-van Ginkel, MD (MPH student at UNC School of Public Health and researcher at Duke Clinical Research Institute in Pediatric Pharmacoepidemiology)

Up Next - Final Spring/Weekly Session (24 April):
One Health: A Concept for the 21stCentury
Laura Kahn, MD, MPH, MPP, Department of Science & Global Security at Princeton University