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Aplastic anemia (AA) is an immune-mediated disease. Although most patients are responsive to immunosuppressive therapy (IST) with a combination of anti-thymocyte globulin (ATG) and cyclosporine (CsA), some patients relapse or are refractory to IST. Sirolimus (rapamysin) inhibits the serine–threonine kinase mammalian target of rapamysin (mTOR), and blocks CsA-resistant and calcium-independent pathways late in the progression of the T-cell cycle. We report two cases of AA which relapsed after CsA and ATG plus CsA, respectively. They achieved transfusion independence after retreatment with sirolimus in combination with a CsA. Pediatr Blood Cancer 2011;56:1133–1135. © 2011 Wiley-Liss, Inc.