Horse ATG/CsA in Aplastic Anemia Patients Unresponsive to or With a Suboptimal Response to Rabbit ATG/CsA Treatment

Study Summary

Background: * Severe plastic anemia can lead to problems with bone marrow platelet production and result in low blood platelet counts, which require frequent platelet transfusions to improve blood clotting. * A standard treatment for SAA involves injections of rabbit-antithymocyte globulin (r-ATG). r-ATG is developed by injecting horses with a type of human white blood cells called thymocytes. The horse's immune system reacts against these cells and makes antibodies that can destroy them. These antibodies are collected and purified to make r-ATG. Horses can also be used for this procedure to make horse-antithymocyte globulin (h-ATG). * h-ATG is approved by the Food and Drug Administration for the treatment of aplastic anemia. h-ATG is a standard first-line method to treat aplastic anemia, but researchers do not know how effective it is in patients who were first treated unsuccessfully with r-ATG. Objectives: \- To evaluate the effectiveness and safety of horse-ATG (with cyclosporine) in increasing blood counts and reducing the need for transfusions in aplastic anemia patients who have failed to respond to prior immunosuppressive treatment with rabbit-ATG and cyclosporine. Eligibility: \- Patients 2 years of age and older who have consistently low blood platelet counts related to aplastic anemia that has not responded to conventional treatment with rabbit-ATG. Design: * After initial screening, medical history, and blood tests, patients will be admitted to the inpatient unit at the National Institutes of Health Clinical Center. Researchers will perform a skin test with h-ATG to check for allergic or other adverse reaction. * After the skin test, h-ATG will be given into a vein continuously over 4 days. * Cyclosporine will also be given to improve the response rate of ATG treatment. Treatment with cyclosporine will start the same day as the h-ATG, either in liquid or capsule form, and continued for 6 months. The dose of cyclosporine will be monitored and adjust

Primary Outcome

The primary endpoint was hematologic response at 3 months, defined as no longer meeting criteria for Severe Aplastic Anemia (SAA) defined as bone marrow cellularity of less than 30% and severe pancytopenia with at least two of the following peripheral blood count criteria: (i) absolute neutrophil count less than 0.5×109/L; (ii) absolute reticulocyte count less than 60×109/L; and (iii) platelet count less than 20×109/L. A complete response was defined as absolute neutrophil count (ANC) above 1.0

Interventions

• DRUG h-ATG (ATGAM )
• DRUG Cyclosporine (Gengraf )