Treatment of refractory or relapsed acquired aplastic anemia: review of established and experimental approaches

In a substantial number of patients with aplastic anemia (AA), immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CSA) leads to long-lasting remissions and is thus regarded as standard therapy. However, no consensus exists on how to treat refractory or relapsed AA, especially when no related stem cell donor is available. For selected patients, matched unrelated donor stem cell transplant (MUDSCT) is an option. In addition, umbilical cord blood and haploidentical donors have been considered as an alternative source of stem cells. Patients without a suitable donor may benefit from a second cycle of ATG and CSA. Alternatives are alemtuzumab and high dose cyclophosphamide, both of which induce remission in more than 50% of patients with relapsed AA. Further experimental drugs are androgens, hematopoietic growth factors (interleukins IL-3, IL-6, and IL-11 and stem cell factor [SCF]), and the tumor necrosis factor (TNF)-targeting agent etanercept. Clinical trials with these agents are ongoing and will explore long-term outcomes and potential beneficial effects of drug combinations.