Complications
Higher rates of graft failure in patients who received a transplant for aplastic anemia (AA) than in those receiving a transplant for other indications.[111]
Two potential reasons: 1) the conditioning regimens for AA are nonmyeloablative, 2) antihematopoietic immune activity is present in the host at the time of transplantation.
Therapy-related complications associated with conditioning regimens (chemotherapy or radiation therapy) may occur: increased risk of growth abnormalities (for children); infertility (fertility is usually well preserved using cyclophosphamide 200mg/kg conditioning)[114]; cataracts (not obviously increased, when irradiation is not given); hypothyroidism[115]; secondary solid tumors (with a 20-year risk around 2% in patients who have received radiation).[116]
Increased risk of developing avascular necrosis, perhaps related to the dose of corticosteroids given concomitantly.[117] Registry data suggest an increased risk in patients with dyskeratosis congenita.
Hepatotoxicity (e.g., liver dysfunction, hepatomas, and peliosis hepatis) and virilization (in women) are complications associated with androgen therapy, although less so with danazol than with other androgens such as oxymetholone.
Many patients with aplastic anemia (AA) harbor a clinically silent PNH clone at diagnosis that may be identified by flow cytometry. With long-term follow-up, the rate of development of overt PNH is around 10%.[3][108] However, PNH can be successfully treated with the C5 monoclonal antibody eculizumab.
Hematopoietic stem cell transplantation is an option for patients with PNH with coexistent AA, but this is associated with significant morbidity and mortality.
In large case series, cumulative incidence of malignant transformations (MDS and acute myelogenous leukemia) has been found to be 10% to 20%.[3][108] It is unknown why aplastic anemia (AA) is associated with such a high rate of clonal evolution and what the role of immunosuppressive therapy is in promoting those phenomena.[108]
In the setting of idiopathic AA, acquired somatic mutations of certain genes (e.g., ASXL1, DNMT3A, BCOR/BCORL1) have been found to be associated with an increased risk for progression to MDS.[109]
In large case series, cumulative incidence of malignant transformations (myelodysplastic syndrome and AML) is 10% to 20%.[3][108] It is unknown why aplastic anemia is associated with such a high rate of clonal evolution, and what the role of immunosuppressive therapy is in promoting those phenomena.[108]
Use of this content is subject to our disclaimer