Evaluation of Chronic GVHD and Anti-ICOS mAb Therapy

A diagnosis of chronic GVHD was based on clinical findings which included generalized skin ulcerations, facial edema, dry eye syndrome, erythema of the sclera, rhinitis, gingivitis, elevated liver enzymes, anorexia, vomiting and or diarrhea. The dogs were monitored at a minimum twice daily and the progression of chronic GVHD was recorded in a digital program DVMax (Veterinary Health Management Software, Westbrook, ME). Once chronic GVHD was established clinically, dogs were administered 3 injections IV of 4.0 mg/kg anti-ICOS mAb, each injection separated by 72 hours (Figure 1). When chronic GVHD of the skin was apparent, confirmation was established by skin biopsy and evaluation by histopathology. Dogs were monitored for remission or progression of disease at a minimum of twice daily. A consensus decision to euthanize an HCT recipient was made by the principle investigator, clinical veterinarian, and animal technicians currently on hand when diminished activity, failure to eat, a greater than 30% loss of weight, or signs of distress were observed. Following euthanasia, a complete necropsy was performed and representative tissues fixed in 10% buffered formalin, embedded in paraffin, sectioned and stained with hematoxylin and eosin for evaluation by two pathologists (G.S., S.P.). Chronic GVHD was graded from mild to severe based on the degree of lymphocyte infiltration and the degree of tissue damage (apoptosis, necrosis, fibrosis, granulation tissue formation, lichenoid and sclerodermatous lesions).