1. Date of download: 6/22/2016 From: Acquired Aplastic Anemia Ann Intern Med. 2002;136(7):534-546. doi:10.7326/0003-4819-136-7-200204020-00011 Venn diagram showing possible relationships among bone marrow failure syndromes.These syndromes include clonal diseases (paroxysmal nocturnal hemoglobinuria, myelodysplasia, and large granular lymphocytosis); and single hematopoietic lineage deficiency diseases (agranuloyctosis, pure red-cell aplasia, and amegakaryocytic thrombocytopenia); note especially the areas of overlap between aplastic anemia and paroxysmal nocturnal hemoglobinuria and myelodysplasia. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

2. Date of download: 6/22/2016 From: Acquired Aplastic Anemia Ann Intern Med. 2002;136(7):534-546. doi:10.7326/0003-4819-136-7-200204020-00011 Pathophysiology and treatment of aplastic anemia.GVHDThe left panel illustrates induction of disease by an inciting event (for example, viral infection or chemical exposure) followed by an aberrant immune response that leads to destruction of hematopoietic stem cells and progenitor cells. When destruction is sufficiently advanced, pancytopenia and clinical disease result. Hematopoietic stem-cell transplantation both replaces the missing hematopoietic cells and is potently immunosuppressive. Immunosuppression reduces or eliminates the aberrant immune process. Late complications of transplantation include graft failure or relapse (presumably caused by resurgent autoimmune attack) and, more frequently, graft-versus-host disease ( ) and infection. Immunosuppressive therapies based on antithymocyte globulin can often partially or fully improve blood cell counts and stem-cell recovery, but patients are susceptible to recurrence of pancytopenia or the development of other hematologic diseases (such as myelodysplasia). Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

3. Date of download: 6/22/2016 From: Acquired Aplastic Anemia Ann Intern Med. 2002;136(7):534-546. doi:10.7326/0003-4819-136-7-200204020-00011 Results of treatment in patients with acquired aplastic anemia. A.(31)B(31)C(32)Allogeneic bone marrow transplantation. Data are presented from individual hospital series in peer-reviewed publications from 1991 to 1997. The shaded area represents the 5-year probability of survival (with the same confidence intervals) of patients reported to the International Bone Marrow Transplant Registry (IBMTR) during this period. Adapted with permission from Horowitz ; original source provides detailed information on each series.. The continuing influence of age on survival, as reflected in IBMTR data. Adapted with permission from Horowitz.. Comparative probability of survival after immunosuppression and bone marrow transplantation. The data are for patients reported to the Working Party on Severe Aplastic Anemia of The European Group for Blood and Marrow Transplantation in the 1980s and 1990s. Adapted with permission from Bacigalupo et al. ; CSA = cyclosporine; FHCRC = Fred Hutchinson Cancer Research Center; MTX = methotrexate; UCLA = University of California, Los Angeles. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

4. Date of download: 6/22/2016 From: Acquired Aplastic Anemia Ann Intern Med. 2002;136(7):534-546. doi:10.7326/0003-4819-136-7-200204020-00011 Immunosuppressive therapies.Activated T cells, shown as enlarged, attack and destroy hematopoietic stem-cell targets. Some drugs inhibit lymphocyte function. Others are broadly lymphocytotoxic. Laboratory and animal data show that agents relatively selective for activated lymphocytes can induce tolerance by eliminating functionally active T-cell clones. Antithymocyte globulin, cyclosporine, and cyclophosphamide have been used to treat aplastic anemia, alone and in combination. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians