An allogeneic bone marrow transplant (with a matched donor) is a powerful treatment against cancers such as lymphoma and leukemia. The main difference between an allogeneic transplant and an autologous transplant is the powerful immunotherapy component that an allogeneic transplant provides. This immunotherapy component, known as graft vs. host disease (GvHD) leads to secondary graft vs tumor (GVT), which is what makes an allogeneic transplant so effective. GVT is responsible for the higher published cure rates in bone marrow transplants performed with the help of infused donor stem cells. Careful management of the GvHD response is crucial to the success of the transplant.
Graft versus Lymphoma (Tumor)
In an allogeneic bone marrow transplant, apheresis is performed to collect the matched donor dog's hematopoietic stem cells. These are cells that originate in the dog’s bone marrow, and will eventually become healthy white blood cells that make up the backbone of the immune system. Immediately following total body irradiation of the recipient dog (with cancer), these cells are given in a vein and find their way into the bone marrow. Engraftment happens when the donor’s stem cells successfully start to produce mature white blood cells that enter into the patient’s blood stream. An immunosuppressant medication is used to carefully manage this phase of transplant. Once engraftment occurs, the new donor white blood cells will begin to attack some of the recipient dog's tissues, including the patient’s cancerous lymphocytes that weren’t killed by total body irradiation. This leads to GvHD and, since the transplanted dog’s cancer cells are of recipient origin, the secondary effect, GVT (lymphoma in this setting). As engraftment progresses, what can be described as a “battle” between the new immune system and the old, plays out in the bone marrow, blood stream and lymph nodes. In a successful bone marrow transplant, total body irradiation and GVT work together to eliminate any remaining cancer cells in the body.
When A Battle Becomes a War- Graft versus Host Disease (GvHD)
Dogs who are treated with an allogeneic bone marrow transplant develop some level of GvHD. They initially take an immunosuppressant drug so they don’t reject the new “foreign” stem cells. Once engrafted with a “new” immune system of donor origin, this drug is stopped. If acute GvHD starts occurring, it usually starts ~10-14 later. Some dogs develop clinical signs of GvHD (patchy skin lesions, elevated liver values) and some don’t. We allow some level of clinical GvHD to occur since the donor cells are also attacking the recipient's cancer cells, leading to GVT. Closecollaboration and communication between the pet parent, primary oncologist and CTAC team is essential during this time to ensure that the GvHD does not harm the recipient dog.
Symptoms of Acute vs. Chronic GvHD
Acute (occurs within the first 100 days post-engraftment):
Chronic (occurs >100 days post-engraftment):- Vomiting- Diarrhea with blood or mucous- Loss of GI tract wall layers-
While not every patient undergoing an allogeneic bone marrow transplant develops clinical GvHD, recovery from bone marrow transplant is an ongoing journey and close communication between the pet parent, local veterinary team and CTAC is vital to the pursuit of a cure from this incurable disease.
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