Acute Myeloid Leukemia (AML)
Diagnosis & Staging
Updated: September 2010
Diagnosis
The diagnosis of AML is a medical emergency that requires referral of the patient to a tertiary referral center with expertise in the management of this disease and its complications. In British Columbia adult patients with an established or probable diagnosis of AML should be referred to the Leukemia/BMT Program at the Vancouver General Hospital. Children should be referred to the BC Children’s Hospital.
Required Tests
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CBC and differential
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Electrolytes, BUN, creatinine, uric acid, liver function tests
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INR, PTT and fibrinogen
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Bone marrow aspirate and biopsy with cytogenetic analysis and flow cytometry for blast cell immunophenotyping. Additional molecular testing may be done depending on the results of cytogenetic analysis (see below under Prognosis).
PLEASE NOTE: TO ENSURE THAT ALL NECESSARY TESTING IS DONE FOR DIAGNOSTIC AND PROGNOSTIC PURPOSES BONE MARROW TESTING IS DONE AT THE VANCOUVER GENERAL HOPSITAL ON ALL NEWLY DIAGNOSED AML PATIENTS REGARDLESS OF WHETHER OR NOT PRIOR MARROW EXAMINATION HAS BEEN DONE.
Thus, if the diagnosis of AML is obvious from the peripheral blood (e.g., high peripheral blood blast cell count) the patient should be referred to the Leukemia/BMT Program without performing a bone marrow examination.
The diagnosis of AML requires:
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More than 20% blasts in the bone marrow differential
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Further refinement of the diagnosis to allow classification of the subtype of AML by WHO criteria requires the results of immunophenotyping and cytogenetics (J Clin Oncol 17:3835-3849, 1999).
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At diagnosis the most important subtype recognition is acute promyelocytic leukemia (APL). Although this is a highly curable AML subtype it carries with it a high risk of hemorrhagic complications and requires specific therapy. See specific Cancer Management Guidelines for APL.
Prognosis
At diagnosis, the average age of patients with AML is 68 years. Survival and likelihood of cure with conventional therapy decreases with age such that although ~40% of adults under 60 years old can be cured with chemotherapy that proportion is less than 10% in patients over 60. Those greater than age 70 have a particularly grim prognosis with median survival from diagnosis of ~6 months. Patients with an antecedent hematologic disease (e.g., myelodysplastic or myeloproliferative disorder) or treatment-related AML also have a less favorable prognosis than patients with de novo AML.
The most powerful disease prognostic indicator is bone marrow cytogenetics. Using the classification developed by the MRC (UK) (Blood 116:354-365, 2010) chromosome abnormalities classify patients as good, intermediate or poor risk. The frequency of adverse cytogenetic abnormalities increases with age. Almost half of AML patients have normal bone marrow cytogenetics at diagnosis. These are classified as intermediate risk. However, there are a growing number of submicroscopic mutations and rearrangements that may also affect prognosis. Currently the Leukemia/BMT Program is using detection of mutations in the FLT3 and NPM1 genes (performed by the BCCA Cancer Genetics Laboratory) to further refine prognosis among patients with intermediate risk cytogenetic changes (N Engl J Med 358:1909-1918, 2008). Below are the current risk categories utilized by the Leukemia/BMT group to stratify post induction therapy for AML patients who are potential stem transplant candidates.
Risk Categories
Good risk
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t(8;21) or inv(16)
OR
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Intermediate risk cytogenetics with good risk molecular testing, i.e. FLT3 ITD –ve; NPM1 mutation +ve
AND
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One or 2 cycles of 7+3 to enter CR
Poor risk
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Cytogenetics (excluding cases with favourable karyotype):
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Intermediate risk cytogenetics and FLT-3 ITD +ve, particularly when NPM1 –ve
OR
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salvage chemo after 1 or 2 cycles of 7+3 required to achieve CR 1
Intermediate risk
- All other cytogenetic abnormalities not described under good and poor risk
AND - FLT3 ITD and NPM1 mutation negative
AND - 1 or 2 cycles of 7 + 3 to enter CR 1
| 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 patient’s care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BC’s terms of use available at Terms of Use. |