Bone marrow failure: causes and complications

Aplastic anaemia (AA), a rare but serious form of bone marrow failure (BMF), is characterized by pancytopenia with hypocellular bone marrow. The pathophysiology of acquired AA is predominantly immunologically mediated, with damage to haemopoietic stem cells by autoreactive T lymphocytes. The aberrant immune response can be triggered by environmental triggers, such as drugs, toxins, chemicals and viral infections, especially after seronegative hepatitis. A careful medical and family history, physical examination and investigations are required to rule out rarer inherited causes of BMFs, as well as other acquired diseases, such as hypoplastic myelodysplastic syndrome, with a similar phenotype. The clinical spectrum of acquired AA varies: some patients with mild cytopenia do not require therapy; others have life-threatening complications resulting from severe pancytopenia. The autoimmune basis provides the rationale for treatment, with either combined immunosuppressive therapy using horse antithymocyte globulin and ciclosporin with eltrombopag, or allogeneic haemopoietic stem cell transplantation (HSCT). Long-term survival of 70–80% can be expected from these standard therapeutic modalities. Recurrence of pancytopenia, secondary to relapse, clonal evolution to myelodysplastic syndrome and paroxysmal nocturnal haemoglobinuria are late sequelae after immunosuppressive therapy. By contrast, HSCT provides the chance of long-term cure.