Aplastic anemia: Current state of diagnosis and treatment

Abstract

Aplastic anemia (AAI) is a rare life-threatening disorder which is characterized by bi- or tricytopenia and hypoplastic or aplastic bone marrow. AA can present as an acquired or congenital disorder. In recent years it was noted that a subgroup of patients with seemingly acquired AA with onset in adulthood carry mutations which cause or at least predispose to bone marrow failure, e.g. mutations in the genes of the telomerase complex. Options for first-line treatment are allogeneic stem cell transplantation or immunosuppression. The decision depends on severity of the disease, age and comorbidity of the patient and availability of a matched stem cell donor. Probability of survival after HLA-identical sibling transplantation exceeds 90% in young patients with bone marrow as the stem cell source and conditioning with an ATG-containing regimen. Results of matched unrelated donor transplantation have improved substantially over the last 10 years. Matched unrelated donor transplantation is increasingly considered as the first-line treatment for very young patients who are candidates for transplantation, but lack an HLA-identical sibling donor. The gold standard for immunosuppression is the combination of antithymocyte globulin (ATG) and cyclosporine A (CsA). ATG, a polyvalent antibody preparation, is obtained from animals after immunization with human thymocytes. Response rate and overall survival after horse ATG treatment are significantly higher compared to rabbit ATG. Recent trials reported a surprisingly high rate of bi- and trilinear response to treatment with the thrombopoietin receptor agonist eltrombopag in patients refractory to immunosuppression. Ongoing trials now address the potential role of eltrombopag as an adjunct to immunosuppression in first-line treatment.