Initial Diagnostic Workup for Acute Myeloid Leukemia (AML)

The 2019 National Comprehensive Cancer Network (NCCN) Guidelines recommend a comprehensive evaluation for suspected AML including bone marrow aspirate and biopsy using morphologic, cytochemical, immunophenotypic, and cytogenetic/molecular analyses. The following graphic illustrates a more in-depth overview of the evaluation.1

Diagnosis of AML: NCCN Guidelines Initial Evaluation

  • History and physical (H&P)
  • Complete blood cell (CBC) count, platelets, differential, comprehensive metabolic panel, uric acid, lactate dehydrogenase (LDH)
  • Prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen
  • Bone marrow core biopsy and aspirate analyses, including immunophenotyping and cytochemistry
  • Cytogenetic analyses (karyotype + FISH)
  • Molecular analyses (KIT, FLT3 [ITD and TKD], NPM1, CEBPA, IDH1, IDH2, TP53, and other mutations)a
  • Comprehensive pathology report, including diagnosis of AML with recurrent cytogenetics vs AML NOS, blast count, cellularity, morphologic dysplasia, and mutation status if available
  • Human leukocyte antigen (HLA) typing for patient with potential hematopoietic cell transplantation (HCT) in the future (except for patients with a major contraindication to HCT)
  • CT of brain without contrast, if CNS hemorrhage suspectedb
  • Brain MRI with contrast, if leukemic meningitis suspectedb
  • PET/CT, if clinical suspicion for extramedullary disease
  • Lumbar puncture (LP), if symptomaticb (category 2B for asymptomatic)
  • Evaluate myocardial function (echocardiogram or MUGA scan) in patients with a history or symptoms of cardiac disease or prior/planned exposure to cardiotoxic drugs or radiation to thorax
aA variety of gene mutations are associated with specific prognoses (category 2A) and may guide medical decision making (category 2B). Other mutations, such as FLT3 -ITD, FLT3- TKD, IDH1/2, NPM1, and c-KIT may have therapeutic implications. The field of genomics in myeloid malignancies, and related implications in AML, are evolving rapidly. While the above mutations should be tested in all patients, multiplex gene panels and next-generation sequencing analysis may be used to obtain a more comprehensive prognostic assessment (Papaemmanuil E, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 2016;374:2209-2221). If a test is not available at your institution, consult the pathology team (prior to performing the marrow evaluation) about preserving material from the original diagnostic sample for future testing at an outside reference lab. Peripheral blood may alternatively be used to detect molecular abnormalities in patients with morphologically detectable, circulating leukemic blasts.
bFor patients with major neurologic signs or symptoms at diagnosis, appropriate imaging studies should be performed to detect meningeal disease, chloromas, or CNS bleeding. LP should be performed if no mass lesion is detected on the imaging study. Screening LP should be considered at first remission before first consolidation for patients with monocytic differentiation, mixed phenotype acute leukemia, WBC >40,000/mcL at diagnosis, extramedullary disease, or high-risk APL. Consider administration of one dose of IT chemotherapy (methotrexate or cytarabine) at time of diagnostic LP.

Reference: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.1.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed January 29, 2019. To view the most recent and complete version of the guideline, go online to The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.