Mesenchymal Stem Cells in the Treatment of Relapsed/Refractory Severe Acquired Aplastic Anemia

Mesenchymal stem cells have been tested in many autoimmune disorders with encouraging results and may be an alternative to the treatment of immune-mediated severe acquired aplastic anemia.

Acquired aplastic anemia is a bone marrow failure syndrome characterized by and empty bone marrow and low blood counts. Most of the cases are immune-mediated. Allogeneic bone marrow transplant is the preferable treatment modality for patients younger than 40 years with a matched sibling donor. Patients not eligible for transplant are treated with intensive immunosuppressive therapy often based on anti-thymocyte globulin and cyclosporine. However, up to one third of patients treated with immunosuppression are refractory and one third of those who response eventually relapse. Refractory and relapsed cases may be the result of insufficient immunosuppression and these cases may benefit from additional immunosuppression. Mesenchymal stem cells infusion may be a potential treatment option, considering its properties to modulate the immune system. Refractory or relapsed patients with aplastic anemia will be treated with conventional immunosuppressive regimen (anti-thymocyte globulin plus cyclosporine) combined with intravenous infusion of allogeneic unrelated bone marrow mesenchymal stem cells.

After standard immunosuppressive therapy with rabbit antithymocyte globulin 3,5 mg/Kg/day during 5 days, allogeneic unrelated bone marrow derived mesenchymal stem cells will be infused intravenously. Oral cyclosporine 5 mg/Kg/day (with dose correction weekly to keep serum cyclosporine level between 150-250 mg/dl) up to 6 months will be added.

Number of Participants with Adverse Events as a Measure of Safety and Tolerability of intravenous allogeneic unrelated mesenchymal stem cells infusion in patients with severe acquired aplastic anemia.

Adverse events like allergic reactions,infectious diseases,organ dysfunction or other related to mesenchymal stem cells infusion will be assessed.

Units of blood or platelets transfused after the mesenchymal stem cells infusion will be measured and compared to previously.

Inclusion Criteria: Diagnosis of Acquired Aplastic Anemia Relapse/refractory to at least 1 immunosuppressive first line treatment Not eligible to allogeneic bone marrow transplantation Exclusion Criteria: Previous or current malignancy Active or latent infectious disease Positive serologic tests for HIV, HCV, HBV, HTLV-1 and 2, Syphilis or Chagas disease Previous drug reaction for antithymocyte globulin, cyclosporin or corticosteroids Severe organic impairment (renal, hepatic, cardiac, pulmonary) Uncontrolled hypertension or diabetes Pregnancy Previous history of allergic reaction to penicillin or streptomycin Severe psychiatric disorder

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