IMMUNE-MEDIATED HEMATOLOGIC DISEASE AND BONE MARROW FAILURE

W. Jean Dodds, D.V.M.
HEMOPET, 938 Stanford Street, Santa Monica, CA 90403

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Immune-mediated hematologic disease is being reported with increasing frequency in animals and humans. In the dog this syndrome is often associated with bone marrow failure. Affected animals usually have one or more of the following signs: autoagglutinating red blood cells; Coombs positive hemolytic anemia; spherocytes; nonregenerative or poorly regenerative erythroid response; severe thrombocytopenia; profound leukopenia; other autoimmune diseases especially thyroiditis; active erythrogenesis, granulocytopoiesis or megakaryocytopoiesis with maturation arrest at the early stem cell level; and poor response to standard treatment protocols with corticosteroids and other immunosuppressive drugs. In many cases a recent stress (e.g. vaccination; drug; chemical or toxic exposure; surgery; hormonal influence; infection; injury) could be identified as a potential triggering event within the previous 30 days.

Our experiences with these cases indicate that:

1) Autoimmune thyroiditis/hypothyroidism is frequently present and/or affected dogs are often of breeds or cross-breeds susceptible to thyroid disease.

2) Aggressive and more sustained treatment with corticosteroids is needed. Suggested doses are: Prednisone or prednisolone given at 2-3 mg/lb/day divided BID for 5-7 days, or examethasone equivalents at 0.254).35 mg/lb/day divided BID. Therapy is reduced weekly by 1/2 and maintained for at least six weeks. Alternate day steroid therapy may be needed for some time thereafter on a longterm, low level basis.

3) For severe cases, other immunosuppressive therapy is given. We prefer Cyclosporine (Sandimmune, 100 mg/ml oral syrup) to cyclophosphamide (Cytoxan) and give it at 10 mg/kg for 5 days rest 2 days, then at 5 mg/kg for another 5 days. The lower dose is repeated after a 2 day rest on a 5 days on, 2 days off cycle as long as is needed (usually 2-3 courses of 5 days). This drug induces rapid T-cell suppression within about 48 hours and has been safe, effective, and well-tolerated at these doses. In cases where sustained more potent immunosuppression is required for clinical stabilization, azathioprine (Imuran) should be instituted along with cyclosporine. Dose is 1 mg/lb/day for 7-10 days Initially followed by a downward tapering over several weeks. Azathioprine may be needed every other day or less often, on a longterm basis. As azathioprine takes about 10 days to effectively suppress T-cells, clinical responsiveness will not occur immediately. Cyclosporine is therefore given concurrently in the early stages of the disease to provide rapid immunosuppression until the azathioprine takes hold.

The goal of this immunosuppressive therapy is to stabilize the ongoing immune destructive process. The dosage guideline we use is adjusted to maintain the absolute lymphocyte count as about 1/3 of the normal range (750-1500/ul).