Background/Objective: Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare disease and is even more rare in children; pediatric cases are estimated to account for <5% of all PNH cases (Ware RE, et al. N Engl J Med. 1991;325:991-996). There is a paucity of published data on outcomes in children with PNH treated with eculizumab. The International PNH Registry (NCT01374360) is a prospective, observational study of patients with PNH regardless of age, and represents the largest cohort of pediatric PNH patients. The objective of this analysis was to evaluate outcomes after initiation of eculizumab in pediatric patients and adult patients enrolled in the Registry.

Survival of patients with aplastic anemia (AA) after both immunosuppression and allogeneic bone marrow transplantation improved substantially over the last 30 years. For patients who received immunosuppressive treatment, this improvement was not restricted to patients who achieve partial or complete remission after specific treatment, but also the prognosis of nonresponders to initial immunosuppression substantially improved over time. This most likely reflects the effect of improved supportive care on the overall survival of patients. The individual risk of a patient for life-threatening infectious complications is mainly determined by the neutrophil- and monocyte counts. During the past two decades, infection-related mortality and the incidence of invasive fungal infections in patients with AA have decreased. However, infections are still the major threat for patients with severe AA or very severe AA. In the most recently published large clinical trials in AA, the most prevalent complication and the major cause of death were still bacterial and fungal infections. In this chapter we summarize recommendations on supportive care. Some aspects have been discussed in details in a previous review of the EBMT Working Party Aplastic Anemia 9 and therefore, here will only be summarized in brief. In this chapter we focus on the role of granulocyte transfusions, transfusion strategy, treatment of iron overload, gender-specific aspects, role of exercise and psychological support for AA, and related bone marrow failures.

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.