Introduction

As the survival of patients with acquired aplastic anemia (AA) improves, patients with autologous marrow recovery have a significant risk of developing malignant disorders of hemopoiesis later in life. The combined cumulative risk of developing myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML) or paroxysmal nocturnal hemoglobinuria (PNH) as a clonal but nonmalignant condition has been calculated to be as high as 40% at 15 years after immunosuppression (Tichelli et al., 1988, 1994). Readers are referred to an excellent review devoted to this issue (Young, 1992) for more details. This chapter focuses on more recent developments, in an attempt to identify patients with AA who are at a high risk of developing MDS or AML as a late clonal complication.

Clinical observations: the evolution of AA to myelodysplastic syndrome and acute myelogenous leukemia

During the past 20 years, treatment of AA has greatly improved, increasing the number of long-term survivors. At the same time, there is mounting evidence that AA is associated with hematological malignancies, as discussed by Dameshek (1967). Table 6.1 summarizes the most meaningful studies which, however, are all retrospective in nature. The evolution of AA to MDS or AML occurs rarely, as compared to transformation to PNH; whilst the exact figure is difficult to establish, it appears to occur in about 10% of cases.