What are the College of American Pathologists and the American Society of Hematology (CAP/ASH) guidelines for the diagnostic workup of acute myeloid leukemia (AML)?

Updated: May 26, 2020
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
  • Print

CAP/ASH guidelines on the initial diagnostic workup of AL include the following recommendations [111] :

  • A complete diagnosis of AL requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping and karyotype analysis, and, often, molecular genetic testing.
  • The treating clinician should provide relevant clinical data, including physical examination and imaging findings, or ensure that those data are readily accessible by the pathologist.
  • The pathologist should review recent or concurrent complete blood cell (CBC) counts and leukocyte differentials and evaluate a peripheral blood (PB) smear.
  • Obtain a fresh bone marrow (BM) aspirate for all patients suspected of AL, a portion of which should be used to make BM aspirate specimens for morphologic evaluation. If performed, the pathologist should evaluate an adequate BM trephine core biopsy, BM trephine touch preparations, and/or marrow clots, in conjunction with the BM aspirates.
  • In addition to morphologic assessment (blood and BM), obtain sufficient samples and perform conventional cytogenetic analysis (ie, karyotype), appropriate molecular-genetic and/or fluorescence in situ hybridization (FISH) testing, and flow cytometry immunophenotyping (FCIp). The flow cytometry panel should be sufficient to distinguish acute myeloid leukemia (including acute promyelocytic leukemia), T-ALL (including early T-cell precursor leukemias), B-cell precursor ALL (B-ALL), and AL of ambiguous lineage for all patients diagnosed with AL. Molecular genetic and/or FISH testing does not, however, replace conventional cytogenetic analysis.
  • For patients with suspected or confirmed AL, cytochemical studies to assist in the diagnosis and classification of acute myeloid leukemia (AML) may be requested and evaluated.
  • The treating clinician or pathologist may use cryopreserved cells or nucleic acid, nondecalcified formalin fixed paraffin-embedded (FFPE) tissue, or unstained marrow aspirate or PB specimens obtained and prepared from PB, BM aspirate, or other involved tissues for molecular or genetic studies in which the use of such material has been validated.
  • For patients with ALL receiving intrathecal therapy, a cerebrospinal fluid (CSF) sample should be obtained. The treating clinician or pathologist should ensure that a cell count is performed and that examination/enumeration of blasts on a cytocentrifuge preparation is performed and is reviewed by the pathologist.
  • For patients with suspected or confirmed AL, the pathologist may use flow cytometry in the evaluation of CSF.
  • For patients who present with extramedullary disease without BM or blood involvement, a tissue biopsy should be evaluated and processed for morphologic, immunophenotypic, cytogenetic, and molecular genetic studies, as recommended for the BM.
  • For pediatric patients with suspected or confirmed B-ALL, ensure testing for t(12;21)(p13.2;q22.1); ETV6-RUNX1, t(9;22)(q34.1;q11.2); BCR-ABL1, KMT2A (previously MLL) translocation; iAMP21; and trisomy 4 and 10 is performed.
  • For adult patients with suspected or confirmed B-ALL, ensure testing for t(9;22)(q34.1;q11.2) and BCR-ABL1. In addition, testing for KMT2A (previously MLL) translocations may be performed.
  • For pediatric and adult patients with suspected or confirmed AML of any type, ensure testing for FLT3-ITD. The pathologist or treating clinician may order mutational analysis that includes, but is not limited to, IDH1, IDH2, TET2, WT1, DNMT3A, and/or TP53 for prognostic and/or therapeutic purposes.
  • For patients with suspected acute promyelocytic leukemia (APL), ensure rapid detection of PML-RARA. The treating physician should also order appropriate coagulation studies to evaluate for disseminated intravascular coagulation (DIC).

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!