Diagnosis and Treatment of Aplastic Anemia.
Acquired aplastic anemia (AA) is a rare, life-threatening bone marrow failure (BMF) disorder that affects patients of all ages and is caused by lymphocyte destruction of early hematopoietic cells. Diagnosis of AA requires a comprehensive approach with prompt evaluation for inherited and secondary causes of bone marrow aplasia, while providing aggressive supportive care. The choice of frontline therapy is determined by a number of factors including AA severity, age of the patient, donor availability, and access to optimal therapies. For newly diagnosed severe aplastic anemia, bone marrow transplant should be pursued in all pediatric patients and in younger adult patients when a matched sibling donor is available. Frontline therapy in older adult patients and in all patients lacking a matched sibling donor involves immunosuppressive therapy (IST) with horse antithymocyte globulin and cyclosporine A. Recent improvements in upfront therapy include encouraging results with closely matched unrelated donor transplants in younger patients and the emerging benefits of eltrombopag combined with initial IST, with randomized studies underway. In the refractory setting, several therapeutic options exist, with improving outcomes of matched unrelated donor and haploidentical bone marrow transplantation as well as the addition of eltrombopag to the non-transplant AA armamentarium. With the recent appreciation of frequent clonal hematopoiesis in AA patients and with the growing use of next-generation sequencing in the clinic, utmost caution should be exercised in interpreting the significance of somatic mutations in AA. Future longitudinal studies of large numbers of patients are needed to determine the prognostic significance of somatic mutations and to guide optimal surveillance and treatment approaches to prevent long-term clonal complications.
['Peslak|Scott A|SA|', 'Olson|Timothy|T|', 'Babushok|Daria V|DV|']
D000741:Anemia, Aplastic D001855:Bone Marrow Diseases D016026:Bone Marrow Transplantation D016572:Cyclosporine D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D007165:Immunosuppression Therapy D035781:Siblings D014019:Tissue Donors
Aplastic anemia Bone marrow failure Bone marrow transplant Immunosuppressive therapy Antithymocyte globulin Eltrombopag Clonal hematopoiesis Cyclosporine A