Costs and consequences of immunosuppressive therapy in children with aplastic anemia.

Acquired aplastic anemia (AA) is the most common form of bone marrow failure, generally defined by the effective mismatch between blood cell production in the bone marrow and peripheral demand. While an occasional association with exposure to environmental factors and drugs, or hepatitis is well documented, patient-specific etiologies of marrow aplasia are mostly elusive. Pathophysiologically, idiopathic AA is considered to arise from immune dysregulation, a notion supported by reports of disease remission after autologous recovery following bone marrow stem cell transplantation and inferential laboratory evidence. Population-based studies reveal bimodal incidence peaks in late childhood and among older adults, although treatment strategies are not generally age-specific. Thus, the treatment algorithm for patients diagnosed with AA generally prioritizes matched sibling donor hematopoietic stem cell transplantation, when possible and economically feasible, over immunosuppressive treatment, most often using horse-derived anti-thymocyte globulin and cyclosporine A (CSA) (Figure 1). With similar long-term treatment outcomes of matched sibling donor hematopoietic stem cell transplantation and immunosuppressive treatment, some have argued vigorously that given the excellent tolerability of anti-thymocyte globulin and CSA, preference, especially in older patients, should be given to universal up-front immunosuppressive treatment to avoid the excess transplant-related toxicities that can compromise survival. However, the shortcomings of the ’one-size-fits-all’ approach are also apparent in the youngest patients, some of whom are later found to suffer from syndromic and heritable, rather than acquired marrow failure. Here, stem cell transplantation, including matched unrelated donor hematopoietic stem cell transplantation, would be the indicated treatment, even though misdiagnosis often becomes apparent only after sustained failure to respond to conventional immunosuppressive treatment. On the backdrop of these and other issues, the study of longterm outcomes after immunosuppressive treatment by Kamio et al., published in this issue of the journal reveals some expected age-independent commonalities, but also provides surprising insight into important problems unique to children.