Aplastic anemia: pathophysiology and treatment

Abstract

An immune basis for most patients with aplastic anemia (AA) provides a rationale for immunosuppressive therapy (IST), using antithmyocyte globulin and cyclosporine as one therapeutic modality; hematologic response is observed in up to 75% of patients. Recent advances in understanding the pathogenesis of AA have identified defective telomere maintenance as an important explanation for the onset of marrow failure, relapse and clonal evolution after IST, in some patients with AA. The finding of inherited mutations in the telomerase gene complex in patients with apparent acquired AA has important implications for clinical management. Hematopoietic stem cell transplantation (HSCT) for acquired AA, whether from an HLA identical sibling or an unrelated donor, provides an excellent chance of long term cure. Current issues with HSCT include graft rejection, chronic GVHD and poor outcome in older patients. The lack of a suitable bone marrow donor for all patients who need a transplant, illustrates the need for novel transplant procedures, such as cord blood transplantation.

Figure 1

Survival up to 10 years for patients (n=2400) with severe aplastic anemia treated with ATG reported to the European Group for Blood and Marrow Transplantation (EBMT) database having received ATG ± CSA as a first line treatment. Patients were treated between 1973-2007. Five-year survival probabilities are: 49±7% for patients treated between 1973-1980 (n=178), 62 ± 3% for those treated between 1980-1990 (n=850), 74 ± 3% for patients treated between 1990-2000 (n=928) and 72 ± 6% for those treated between 2000-2007 (n=444).

Figure 2

Treatment of acquired severe aplastic anaemia CRP, clinical research protocol; IST, immunosuppressive therapy; UCB, umbilical cord blood; MUD, matched unrelated donor; CSA, ciclosporin; HLA id sib, HLA identical sibling. * For patients older than 60 years, there is currently insufficient data on the role of HSCT in severe AA although data for MDS suggests that this may be a future option (see text).

Figure 3

Actuarial survival of SAA patients undergoing a BMT from HLA identical siblings or from alternative donors. In the period 1991-96 the difference in actuarial survival is greater than 35%. In the period 1997-2002 the difference is reduced to less than 15% (data from the EBMT WPSAA)

Figure 3

Actuarial survival of SAA patients undergoing a BMT from HLA identical siblings or from alternative donors. In the period 1991-96 the difference in actuarial survival is greater than 35%. In the period 1997-2002 the difference is reduced to less than 15% (data from the EBMT WPSAA)