Aplastic anemia in children: Pathogenetic mechanisms and current therapy

Aplastic anemia (AA) is a severe, acquired hematological disease, which is usually idiopathic. There are two peaks of incidence, at 15-25 years and above 60 years. In children under the age of 15 years, there are 1-3 cases per 106 children, and at this age it is of utmost importance to recognize possible congenital bone marrow failure syndromes. There is no single hallmark for the diagnosis of AA. Decreased bone marrow cellularity and function are evidenced by a decrease in the peripheral blood count, with concomitant hemorrhage, infection and pallor. In the majority of cases, AA is the result of an autoimmune destruction mechanism targeted at the subject's own bone marrow cells. A usually unidentified triggering event leads to a Th1 type cell response, with overproduction of myelosuppressant cytokines, such as IFN-alpha, TNF-alpha and IL-2, in parallel with activation of Fas mediated, increased bone marrow cell apoptosis. Appropriate therapy results in reversal of the above pathways and clinical cure. There is a possibility of later evolution to clonal disease, i.e., myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). The forms of treatment available for AA are appropriate immunosuppressive therapy (IST) or stem cell transplantation (SCT). IST comprises anti-thymocyte globulin and cyclosporine. SCT is the treatment preferred for younger patients with severe AA who have an available HLA compatible sibling donor, and in the case of IST failure (with the use of volunteer donors). IST is reserved for older patients and for younger patients without an available sibling donor. Currently treatment results achieve a 75% to 85% 5-year survival rate. Extremely important issues in the care of patients with AA are prompt diagnostic evaluation and the meticulous supportive care.