Tests
1st tests to order
CBC with differential
Test
Most patients with AML or acute promyelocytic leukemia (APL) have anemia, neutropenia, and/or thrombocytopenia, but blood count can vary greatly.
An elevated white blood cell (WBC) count >100,000/microliter (>100 × 10⁹/L; hyperleukocytosis) occurs in approximately 5% to 20% of patients with AML, predisposing them to complications such as tumor lysis syndrome, central nervous system involvement, and leukostasis (symptomatic hyperleukocytosis; symptoms include respiratory distress and altered mental status).[3][4] These are medical emergencies and require immediate treatment. Despite the elevation in WBC count, many patients have severe neutropenia (<500 granulocytes/microliter [<0.5 × 10⁹ granulocytes/L]), thus placing them at high risk for serious infections.
Result
anemia, macrocytosis, leukocytosis, neutropenia, and/or thrombocytopenia
peripheral blood smear
Test
Blasts are immature cells and are not normally seen in the peripheral blood.
AML is characterized by myeloid blasts with Auer rods or Phi bodies.
Acute promyelocytic leukemia (APL) is characterized by hypergranular promyelocytes with bilobed nuclei and bundles of Auer rods (as well as myeloid blasts).
A variant of APL is characterized by hypogranular promyelocytes (absence of Auer rods), but is less common.[Figure caption and citation for the preceding image starts]: Peripheral blood film of a patient with acute myeloid leukemia with maturation showing myeloid blasts with an Auer rodFrom the collection of Drs K. Raj and P. Mehta; used with patient consent [Citation ends].
[Figure caption and citation for the preceding image starts]: Peripheral blood film of a patient with acute promyelocytic leukemia showing hypergranular promyelocytes with bilobed nuclei and bundles of Auer rodsFrom the collection of Drs K. Raj and P. Mehta; used with patient consent [Citation ends].
[Figure caption and citation for the preceding image starts]: Peripheral blood film of a patient with acute promyelocytic leukemia showing hypergranular promyelocytes, some with bundles of Auer rodsFrom the collection of Drs K. Raj and P. Mehta; used with patient consent [Citation ends].
Result
myeloid blasts on blood film; presence of Auer rods or Phi bodies (in AML); presence of hypergranular promyelocytes with bilobed nuclei and bundles of Auer rods, or hypogranular promyelocytes without Auer rods (in APL)
coagulation panel
Test
Ordered as baseline and monitored throughout treatment.
Prothrombin time (PT) and activated partial thromboplastin time (aPTT) may be mildly prolonged with normal fibrinogen and D-dimer.
If these tests are abnormal (prolonged PT and aPTT, decreased fibrinogen, and/or elevated D-dimer), disseminated intravascular coagulation (DIC) should be suspected and an urgent referral is warranted. Refer to the International Society on Thrombosis and Haemostasis (ISTH) scoring system for DIC.[52]
DIC occurs most frequently in acute promyelocytic leukemia (APL).
Severely decreased fibrinogen suggests primary fibrinolysis.
Result
PT, aPTT, fibrinogen, and/or D-dimer may be normal or abnormal; if abnormal, DIC should be suspected
serum electrolytes
Test
Ordered as baseline and monitored throughout treatment.
Hyperkalemia, hypocalcemia, and hyperphosphatemia (together with hyperuricemia and elevated serum lactate dehydrogenase) may occur due to tumor lysis syndrome (TLS), particularly during treatment and if white blood cell count (tumor burden) is high. This can lead to cardiac arrhythmias, seizures, acute renal failure, and death, if untreated. TLS is an oncologic emergency.[51] See Tumor lysis syndrome.
Hypercalcemia may occur due to bony infiltration or ectopic release of a parathyroid hormone-like substance.
Result
serum potassium and phosphorus may be elevated; serum calcium may be decreased or elevated
serum uric acid
Test
Ordered as baseline and monitored throughout treatment.
Hyperuricemia (together with hyperkalemia, hypocalcemia, hyperphosphatemia, and elevated serum lactate dehydrogenase) may occur due to tumor lysis syndrome (TLS), particularly during treatment and if white blood cell count (tumor burden) is high. This can lead to cardiac arrhythmias, seizures, acute renal failure, and death, if untreated. TLS is an oncologic emergency.[51] See Tumor lysis syndrome.
The degree of uric acid elevation may reflect the extent of disease burden and is useful for prognosis.[55]
Result
may be elevated
serum lactate dehydrogenase (LDH)
Test
Ordered as baseline and monitored throughout treatment.
Elevated serum LDH (together with hyperkalemia, hypocalcemia, hyperphosphatemia, and hyperuricemia) may occur due to tumor lysis syndrome (TLS), particularly during treatment and if white blood cell count (tumor burden) is high. This can lead to cardiac arrhythmias, seizures, acute renal failure, and death, if untreated. TLS is an oncologic emergency.[51] See Tumor lysis syndrome.
The degree of LDH elevation may reflect the extent of disease burden and is useful for prognosis.[56]
Result
may be elevated
renal function
Test
Ordered as baseline and monitored throughout treatment.
Includes measurement of BUN and creatinine.
Acute renal failure may occur if tumor lysis syndrome (TLS) develops. TLS is an oncologic emergency.[51] See Tumor lysis syndrome.
Result
may be abnormal if there is renal dysfunction
liver function tests
Test
Ordered as baseline and monitored throughout treatment.
Includes measurement of total bilirubin, albumin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST).
Result
may be abnormal if there is liver dysfunction
bone marrow evaluation
Test
Diagnostic workup includes bone marrow aspirate and trephine biopsy analyses.[23][38]
Cytomorphology assessment demonstrates bone marrow hypercellularity and infiltration by myeloid blasts in AML (as well as hypergranular or hypogranular [less common] promyelocytes in acute promyelocytic leukemia [APL]). Blast cells are negative for terminal deoxynucleotidyl transferase (TdT) and stain positive for myeloperoxidase.
Immunophenotyping (using flow cytometry on bone marrow aspirate) identifies cell surface and cytoplasmic markers of myeloid blasts (e.g., CD34, CD33) and establishes lineage.
Immunohistochemistry (using core biopsy specimen) may be used instead of flow cytometry for immunophenotyping if bone marrow aspirate is unavailable or of poor quality.
Confirmation of a myeloid origin of the leukemic cells by immunophenotyping is essential to differentiate AML and acute lymphoblastic leukemia (ALL), as these are often clinically indistinguishable.
If bone marrow specimens are inadequate or unattainable, then peripheral blood can be used for pathologic assessment provided there are sufficient numbers of circulating blasts.
Result
bone marrow hypercellularity and infiltration by myeloid blasts; presence of Auer rods or Phi bodies (in AML); presence of hypergranular promyelocytes with bilobed nuclei and bundles of Auer rods, or hypogranular promyelocytes without Auer rods (in APL); positive for cell-surface and cytoplasmic markers for myeloid blasts (e.g., CD34, CD33, myeloperoxidase); negative for TdT
genetic testing
Test
Cytogenetic analysis (karyotyping and fluorescence in situ hybridization [FISH]) and molecular genetic testing should be performed to inform the diagnosis, prognosis, and treatment.[23][38]
In AML, the following genetic abnormalities should be investigated due to their association with specific prognoses and treatment targets: RUNX1::RUNX1T1; CBFB::MYH11; MLLT3::KMT2A (or other KMT2A rearrangements); DEK::NUP214; BCR::ABL1; KAT6A::CREBBP; c-KIT; NPM1; FLT3 (ITD and TKD); IDH1; IDH2; CEBPA (basic leucine zipper [bZIP] domain); -5 or del(5q); -7; -17/abn(17p); GATA2; MECOM(EVI1); ASXL1; BCOR; EZH2; RUNX1; SF3B1; SRSF2; STAG2; U2AF1; ZRSR2; and TP53.[23][38] See Criteria.
Next-generation sequencing panels and multiplex gene panels are recommended for mutational analysis.[23]
Acute promyelocytic leukemia (APL, a subtype of AML) is characterized by the PML::RARA fusion gene caused by a t(15;17)(q22;q12) balanced chromosomal rearrangement.[23][37]
Result
may identify AML-defining genetic abnormalities
Tests to consider
CNS imaging and lumbar puncture
Test
CNS imaging (e.g., brain MRI or CT scan) should be carried out in patients who present with neurologic signs or symptoms suggesting CNS involvement.[23][38]
A diagnostic lumbar puncture should be carried out if CNS imaging does not identify CNS bleeding, meningeal disease, and a mass lesion, and neurologic signs and symptoms persist. A single dose of intrathecal chemotherapy (e.g., methotrexate or cytarabine) may be considered at the time of diagnostic lumbar puncture.
Coagulopathy should be managed before lumbar puncture, particularly in patients with acute promyelocytic leukemia (APL).
Result
CNS imaging may show intracranial bleeding, leptomeningeal disease, mass lesion; lumbar puncture may detect malignant cells
FDG-PET/CT scan
Test
Should be considered in patients with suspected extramedullary disease.[38]
Result
may show extramedullary lesions
human leukocyte antigen (HLA) typing
Test
Ordered to assess and match for suitable donor for allogeneic stem cell transplant.
Result
variable
chest x-ray
Test
May be performed to identify pneumonia, mediastinal masses, pulmonary infiltrates, or cardiomegaly.
Result
may show evidence of pneumonia, mediastinal masses, pulmonary infiltrates, cardiomegaly
echocardiogram
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