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The Leukemia/Bone Marrow Transplant Program of BC

Healthcare Professionals
Cancer Management Guidelines

Aplastic Anemia

Updated: May 2016


Aplastic anemia (AA) is a rare condition with an annual incidence of 2 new cases per million population. The disease has a biphasic distribution, most frequently affecting teens/young adults and individuals beyond the age of 60 years. It presents with low blood counts (hematologic cytopenias) affecting at least two but often all three cell lines (hemoglobin, white blood cells and platelets) – i.e. "pancytopenia". The bone marrow examination shows an empty ("aplastic") marrow and while the remaining erythroid cells may be somewhat abnormal (dysplastic) in appearance, the white cell precursors and megakaryocytes are morphologically normal. Bone marrow karyotype analysis may fail due to inadequate growth of cells in the culture but, if available, is almost always normal. White cell or megakaryocytic dysplasia or the presence of a clonal karyotypic abnormality should raise the possibility of myelodysplastic syndrome.


AA is classified according to the severity of the low blood counts as follows:


(x 109/L)

(x 109/L)

(x 109/L)

Severe AA (SAA)
[at least 2/3 of the criteria needed]
Very severe AA (VSAA)
Non-severe AA (NSAA)
Not meeting above criteria


The cause of AA is uncertain in more than 90% of patients. The most common established cause is seronegative hepatitis (~5% of patients). Pregnancy and eosinophilic fasciitis are clearly established causes of AA although it rarely develops in pregnancy and the latter condition is exceedingly rare in its own right. Drugs have long been suspected in the development of AA but a clear link has been difficult to establish for any one agent. Epidemiologic studies suggest exposure to certain chemicals (benzene and pesticides) may place individuals at greater risk of developing AA. AA may also be a manifestation of a congenital/constitutional syndrome (e.g. Fanconi anemia or dyskeratosis congenita/telomeropathy). These disorders may present with isolated marrow failure or there may be other associated congenital abnormalities – musculoskeletal, neurologic, cardiac, renal or other.


AA is believed to result from autoimmune destruction of hematopoietic cells by oligoclonal cytotoxic T lymphocytes (CTL). These CTLs are part of the immune system’s reponse to an external challenge but in AA patients, they persist abnormally, possibly as a result of a genetic tendency to do so. CTLs produce interferon-γ and TNF-α which, in turn, damage the hematopoietic tissue. One treatment approach (see below) is to use drugs to "dampen" this abnormal immune response – immunosuppression.


Supportive care remains the mainstay for managing AA patients – transfusion of red blood cells and/or platelets and the administration of antimicrobial agents to combat infections. Definitive therapy is generally between allogeneic bone marrow transplantation (BMT) and immunosuppression (see Treatment Algorithm). Young AA patients with a matched sibling donor will have BMT recommended as the long-term event-free survival is now in the order of 80-85% (see Outcomes). These results have improved through the years through refinement of diagnostic techniques, BMT preparative regimens and better supportive care drugs. Older AA patients and those without a sibling donor will generally be given immunosuppression – a combination of intravenous antithymocyte globulin (ATGAM) for four days, oral Cyclosporine for approximately two years and a short course of corticosteroids (Prednisone). Immunosuppression is associated with a 60-70% partial or complete response rate and, historically, a 60% survival at 10 years (see Outcomes). About one in three responders to immunosuppression will relapse (although 90% never require blood product support, only long-term Cyclosporine maintenance), and 15% of responders develop a clonal disease (such as MDS). Therefore, only ~40% of AA patients treated with immunosuppression will be able to stop all medications and maintain satisfactory blood counts for the remainder of their life. For patients lacking a sibling donor and for those with AA that is relapsed or refractory to immunosuppression, BMT from a volunteer unrelated donor is a viable treatment alternative. Results of unrelated donor BMT for AA have improved significantly through the years (for the same reasons listed above for matched sibling donors; see Outcomes) and long-term event free survival are now in the order of 70-75%.

Treatment options for patients refractory to Cyclosporine/ATGAM and who are unable to undergo BMT include, in addition to ongoing standard supportive care:

  1. Thymoglobulin – another ATG product with an ~30% response rate in patients that fail to respond to ATGAM
  2. Eltrombopag – a daily oral agent that produces an ~40% response rate with ~25% of patients having a multilineage response
  3. Alemtuzumab – an intravenous drug given for 10 days that is associated with a ~30% response rate


Click images to enlarge.

Aplastic Anemia Treatment Algorithm


BCCA Chemotherapy Protocols and PPOs


Aplastic Anemia Outcome Slide 1 Aplastic Anemia Outcome Slide 2


The information contained in these guidelines is a statement of consensus of Leukemia/BMT Program of BC professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patientís care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BCís terms of use available at Terms of Use.

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