Complications

Complication
Timeframe
Likelihood
short term
high

Higher rates of graft failure in patients who received a transplant for AA than in those receiving a transplant for other indications.[50]

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.

variable
high

Acute GVHD affects 10% to 50% of patients.[79][80]

Chronic GVHD affects 20% to 50% of long-term survivors.[79][80]

Graft versus host disease

variable
high

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)[81]; cataracts (not obviously increased, when irradiation is not given); hypothyroidism[82]; secondary solid tumors (with a 20-year risk around 2% in patients who have received radiation).[83]

variable
high

Increased risk of developing avascular necrosis, perhaps related to the dose of corticosteroids given concomitantly.[84] Registry data suggest an increased risk in patients with dyskeratosis congenita.

variable
high

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.

variable
low

Many patients with 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%.[2][76] However, PNH can be successfully treated with the C5 monoclonal antibody eculizumab.

Hematopoietic stem cell transplantation (HSCT) is an option for patients with PNH with coexistent AA, but this is associated with significant morbidity and mortality.

Paroxysmal nocturnal hemoglobinuria

variable
low

In large case series, cumulative incidence of malignant transformations (MDS and acute myelogenous leukemia) has been found to be 10% to 20%.[2][76] It is unknown why AA is associated with such a high rate of clonal evolution and what the role of immunosuppressive therapy is in promoting those phenomena.[76]

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.[77]

Myelodysplastic syndrome

variable
low

In large series, cumulative incidence of malignant transformations (MDS and AML) is 10% to 20%.[2][76] It is unknown why AA is associated with such a high rate of clonal evolution, and what the role of immunosuppressive therapy is in promoting those phenomena.[76]

Acute myelogenous leukemia

variable
low

Cumulative incidence is around 2% after HSCT and about 9% after immunosuppressive therapy.[78][44]

Risk of solid tumor is also significantly increased in inherited marrow failure syndromes, such as Fanconi anemia and dyskeratosis congenita.

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