Therapy related acute myeloid leukaemia (AML)

therapy related acute myeloid leukaemia

Therapy-related AML (t-AML) is a clinical syndrome seen as a complication after cytotoxic and/or radiation therapy (1).

• currently 10% of all AML's occur after treatment with chemotherapy and/or radiation for a primary malignancy or autoimmune disease
• t-AML is associated with an increased prevalence of adverse risk karyotypes
• cumulative dose, dose intensity, and type of preceding chemotherapy and/or radiation therapy may decide the latency period (time between the diagnosis of the primary disease and the development of t-AML)which may be from several months to years

The terms "secondary AML (s-AML)" and "treatment-related AML" are often used interchangeably for AML cases which are thought to have been caused by previous cytotoxic therapy (3).

• however there have been reports that in some patients AML was not associated with previous cancer chemotherapy or radiation and occurred as a second cancer e.g. - AML occurring as a second cancer in patients who were treated with surgery for the primary cancer
• risk factors associated with s-AML are
  • chemotherapeutic agents - topoisomerase II inhibitors (epipodophyllotoxins and anthracyclines), alkylating agents
  • other medications - Dexrazoxane, Azathioprine, G-CSF o radiotherapy
  • host factors - predisposing genetic abnormalities, original cancer
• these cases are now termed as "second de novo" cancers (3)

The outcome is poor in t-AML patients when compared to de novo AML patients.

Several factors such as persistence of the primary malignant disease, injury to organs caused by prior therapy, depletion of normal hematopoietic stem cells, damage to marrow stroma (in particular by radiation therapy) are responsible for the poorer outcome (3).

There is lack of prospective treatment data regarding patients with t-AML since they have often been excluded from frontline clinical trials. Thus during treatment, status of the primary cancer, the patient's performance status, presence of complications from primary therapy and the leukemic karyotype should be considered (1).

Reference:

• 1. Döhner H et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453-74.
• 2. Kayser S et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood. 2011;117(7):2137-45.
• 3. Hijiya N et al. Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer. 2009 Jan 1;115(1):23-35.