Acquired Aplastic Anemia
- Neal S. Young, MD
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From the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
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Figure 1. 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. Venn diagram showing possible relationships among bone marrow failure syndromes.
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Figure 2. The 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). Pathophysiology and treatment of aplastic anemia.GVHD
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Figure 3. 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. Results of treatment in patients with acquired aplastic anemia. A.(31)B(31)C(32)
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Figure 4. 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. Immunosuppressive therapies.
- Copyright ©2004 by the American College of Physicians
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Ann Intern Med
April 2, 2002
vol. 136
no. 7
534-546
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Figure 1. 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. Venn diagram showing possible relationships among bone marrow failure syndromes.
Figure 4. 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. Immunosuppressive therapies.
