Activated T cells also induce apoptosis in hematopoietic stem cells.Aplastic anemia is associated with increased levels of Th17 cells—which produce pro-inflammatory cytokine IL-17—and interferon-γ-producing cells in the peripheral blood and bone marrow. Th17 cell populations also negatively correlate with regulatory T-cell populations, suppressing auto-reactivity to normal tissues, including the bone marrow. Deep phenotyping of regulatory T-cells showed two subpopulations with specific phenotypes, gene expression signatures, and functions.Studies in patients who responded to immunosuppressive therapy found dominant subpopulations characterized by higher expression of HLA‐DR2 and HLA‐DR15 (mean age of two groups: 34 and 21 years), FOXP3, CD95, and CCR4; lower expression of CD45RA (mean age: 45 years); and expression of the IL‐2/STAT5 pathway. Higher frequency of HLA‐DR2 and HLA‐DR15 may cause augmented presentation of antigens to CD4+ T-cells, resulting in immune‐mediated destruction of the stem cells. In addition, HLA‐DR2-expressing cells augment the release of tumor necrosis factor-α, which plays a role in disease pathology.The hypothesis of aberrant, disordered T‐cell populations as the initiators of aplastic anemia is supported by findings that immunosuppressive therapy for T-cells (for example, anti-thymocyte globulin and ciclosporin) results in a response in up to 80% of severe aplastic anemia patients. CD34+ progenitor cells and lymphocytes in the bone marrow over-express the Fas receptor, the main element in apoptotic signaling. A significant increase in the proportion of apoptotic cells in the bone marrow of aplastic anemia patients has been demonstrated.
Many patients with aplastic anemia also have clones of cells characteristic of paroxysmal nocturnal hemoglobinuria (PNH), a rare disease that causes anemia with thrombocytopenia and/or thrombosis and is sometimes referred to as AA/PNH. Occasionally PNH dominates over time, with the major manifestation of intravascular hemolysis. The overlap of AA and PNH has been speculated to be an escape mechanism by the bone marrow against destruction by the immune system. Flow cytometry testing is performed regularly in people with previous aplastic anemia to monitor for the development of PNH. Prognosis
Untreated, severe aplastic anemia has a high risk of death. Modern treatment produces a five-year survival rate that exceeds 85%, with younger age associated with higher survival.Survival rates for stem cell transplants vary depending on the age and availability of a well-matched donor. They are better for patients who have donors that are matched siblings and worse for patients who receive their marrow from unrelated donors. Overall, the five-year survival rate is higher than 75% among recipients of blood marrow transplantation.Older people (who are generally too frail to undergo bone marrow transplants) and people who are unable to find a good bone marrow match have five-year survival rates of up to 35% when undergoing immune suppression.Relapses are common. Relapse following ATG/ciclosporin use can sometimes be treated with a repeated course of therapy. In addition, 10–15% of severe aplastic anemia cases evolve into myelodysplastic syndrome and leukemia. According to one study, 15.9% of children who responded to immunosuppressive therapy eventually relapsed.Milder disease may resolve on its own.