Aplastic Anemia

GENERAL PRINCIPLES

• Aplastic anemia (AA) is a disorder of hematopoietic stem cells that usually presents with pancytopenia.

• Most cases are acquired and idiopathic, but AA can also arise from an inherited BM failure syndrome such as Fanconi anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome.

• Approximately 20% of cases may be associated with drug or chemical exposure.

• Approximately 10% of cases are associated with viral illnesses (e.g., viral hepatitis, Epstein-Barr virus, parvovirus, cytomegalovirus [CMV]).

• Clonal hematopoiesis is a feature of AA, with MDS and AML developing in ~15% of patients.

DIAGNOSIS

Diagnostic Criteria

Prognosis in AA is dependent on disease severity and patient age:

• Moderate or nonsevere AA

î BM cellularity lt;30%

î Absence of criteria for severe AA

î At least two of three blood lines are lower than normal

• Severe AA

î BM cellularity lt;25% with normal cytogenetics, OR

î BM cellularity lt;50% with normal cytogenetics, and lt;30% residual hematopoietic cells, AND two of three peripheral blood criteria:

#9632; Absolute neutrophil count (ANC) lt;500#8725;#956;L

#9632; Platelet count lt;20,000#8725;#956;L

#9632; Absolute reticulocyte count lt;20,000#8725;#956;L

î No other hematologic disease

• Very severe AA

î The criteria of severe AA are met, AND

î ANC lt;200#8725;#956;L

Diagnostic Testing

BM biopsy is required for diagnosis. The BM results in a patient with AA may be difficult to distinguish from hypoplastic MDS; however, both may respond to immunosuppressive therapy (1ST). Paroxysmal nocturnal hemoglobinuria clones can be detected by flow cytometry of the blood or BM.

TREATMENT

• Suspected offending drugs should be discontinued and exacerbating factors corrected. Rarely, spontaneous recovery of normal hematopoiesis can occur, usually within 1-2 months of discontinuing the offending drug.

• Once the diagnosis is established, care should be provided in a center experienced with AA.

• Therapy is optional in moderate AA unless there is transfusion dependence; however, severe or very severe AA requires urgent treatment given the high risk of infectious and hemorrhagic complications.

• Patients younger than 50 years with severe AA should be evaluated for eligibility for allogeneic SCT.

• Patients older than 50 years with severe AA or younger patients without SCT donor are treated with IST with eltrombopag 75-150 mg/d along with cyclosporine and antithymocyte globulin.⁶ Overall response rates at 6 months were 94% and the 2-year survival rate was 97%.

• AA typically does not respond to ESAs. Granulocyte colony-stimulating factor may be effective in some patients and can be used while awaiting definitive therapy; however, there is no clear evidence of survival benefit with the use of these agents.

• Corticosteroids alone have not been shown to be effective and can increase the risk of infections and should not be used in the treatment of AA.

• Transfusions in AA. RBC transfusions should be kept to a minimum to avoid alloimmunization. Prophylactic platelet transfusions are generally recommended if the platelet count is lt;10,000#8725;#956;L. Transfusion of irradiated, leukocyte-depleted blood products is preferred to decrease the risk of alloimmunization.