Last updated January 11, 2022

Initial Diagnostic Workup of Acute Leukemia

Recommendations

The treating clinician should provide relevant clinical data or ensure that this is readily accessible by the pathologist. (S)
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The treating clinician should provide relevant physical examination and imaging findings or ensure that these results are readily accessible by the pathologist. (R)
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The pathologist should review recent or concurrent CBCs and leukocyte differentials and evaluate a peripheral blood smear. (S)
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The treating clinician or pathologist should obtain fresh bone marrow aspirate for all patients who are suspected of AL, a portion of which should be used to make bone marrow aspirate smears for morphologic evaluation. If performed, the pathologist should evaluate an adequate bone marrow trephine core biopsy, bone marrow trephine touch preparations, and/or marrow clots in conjunction with bone marrow aspirates. (S)
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In addition to morphologic assessment—blood and bone marrow—the pathologist or treating clinician should obtain sufficient samples and perform conventional cytogenetic analysis (ie, karyotype), appropriate molecular genetic and/or fluorescent in situ hybridization testing, and flow cytometric immunophenotyping. The flow cytometry panel should be sufficient to distinguish acute myeloid leukemia (AML), including acute promyelocytic leukemia; T-cell acute lymphoblastic leukemia (ALL), including early T-cell precursor leukemias; B-cell precursor ALL (B-ALL); and AL of ambiguous lineage on all patients diagnosed with AL. Molecular genetic and/or fluorescent in situ hybridization testing does not, however, replace conventional cytogenetic analysis. (S)
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For patients with suspected or confirmed AL, the pathologist may request and evaluate cytochemical studies to assist in the diagnosis and classification of AML. (EC)
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The treating clinician or pathologist may use cryopreserved cells or nucleic acid, formalin-fixed, nondecalcified paraffin-embedded tissue, or unstained marrow aspirate or peripheral blood smears obtained and prepared from peripheral blood, bone marrow aspirate, or other involved tissues for molecular or genetic studies in which the use of such material has been validated. Such specimens must be properly identified and stored under appropriate conditions in a laboratory that complies with regulatory and/or accreditation requirements. (R)
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For patients with ALL receiving intrathecal therapy, the treating clinician should obtain a CSF sample. 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 reviewed by the pathologist. (S)
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For patients with AL other than those with ALL who are receiving intrathecal therapy, the treating clinician may, under certain circumstances, obtain a CSF sample when there is no clinical contraindication. 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 reviewed by the pathologist. (EC)
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For patients with suspected or confirmed AL, the pathologist may use flow cytometry in the evaluation of CSF. (R)
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For patients who present with extramedullary disease without bone marrow or blood involvement, the pathologist should evaluate a tissue biopsy and process it for morphologic, immunophenotypic, cytogenetic, and molecular genetic studies, as recommended for bone marrow. (S)
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For patients with suspected or confirmed AL, the pathologist or treating clinician should ensure that flow cytometry analysis or molecular characterization is comprehensive enough to allow for the subsequent detection of minimal residual disease. (S)
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For pediatric patients with suspected or confirmed B-ALL, the pathologist or treating clinician should ensure that testing for t(12;21)(p13.2;q22.1); ETV6-RUNX1, t(9;22)(q34.1;q11.2); BCR-ABL1,KMT2A (MLL) translocation, iAMP21, and trisomy 4 and 10 is performed. (S)
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For adult patients with suspected or confirmed B-ALL, the pathologist or treating clinician should ensure that testing for t(9;22)(q34.1;q11.2); BCR-ABL1 is performed. In addition, testing for KMT2A (MLL) translocations may be performed. ()
(Strong recommendation for testing for t(9;22)(q34.1;q11.2) and BCR-ABL1Recommendation for testing for KMT2A [MLL] translocations)
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For patients with suspected or confirmed ALL, the pathologist or treating clinician may order appropriate mutational analysis for selected genes that influence diagnosis, prognosis, and/or therapeutic management, which includes but is not limited to PAX5, JAK1, JAK2, and/or IKZF1 for B-ALL and NOTCH1 and/or FBXW7 for T-ALL. Testing for the overexpression of CRLF2 may also be performed for B-ALL. (R)
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For pediatric and adult patients with suspected or confirmed AML of any type, the pathologist or treating clinician should ensure that testing for FLT3-ITD is performed. The pathologist or treating clinician may order mutational analysis that includes but is not limited to IDH1IDH2TET2WT1DNMT3A, and/or TP53 for prognostic and/or therapeutic purposes. ()
(Strong recommendation for testing for FLT3-ITD; Recommendation for testing for other mutational analysis)
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For adult patients with confirmed core-binding factor (CBF) AML [AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 or inv(16)(p13.1q22)/t(16;16)(p13.1;q22); CBFB-MYH11], the pathologist or treating clinician should ensure that appropriate mutational analysis for KIT is performed. For pediatric patients with confirmed CBF-AML; RUNX1-RUNX1T1 or inv(16)(p13.1q22) / t(16;16)(p13.1;q22); CBFB-MYH11, the pathologist or treating clinician may ensure that appropriate mutational analysis for KIT is performed. ()
(Strong recommendation for testing for KIT mutation in adult patients with CBF-AML; Expert consensus opinion for testing for KIT mutation in pediatric patients with CBF-AML)
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For patients with suspected acute promyelocytic leukemia, the pathologist or treating physician should also ensure that rapid detection of PML-RARA is performed. The treating physician should also order appropriate coagulation studies to evaluate for disseminated intravascular coagulation. (S)
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For patients other than those with confirmed CBF-AML, acute promyelocytic leukemia, or AML with myelodysplasia-related cytogenetic abnormalities, the pathologist or treating clinician should ensure that mutational analysis for NPM1CEBPA, and RUNX1 is also performed. (S)
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For patients with confirmed AL, no recommendation is made for or against the use of global/gene-specific methylation, microRNA expression, or gene expression analysis for diagnosis or prognosis. ()
(No recommendation)
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For patients with confirmed mixed-phenotype AL, the pathologist or treating clinician should ensure that testing for t(9;22)(q34.1;q11.2); BCR-ABL1, and KMT2A (MLL) translocations is performed. (S)
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All laboratory testing performed for the initial workup and diagnosis of a patient with AL must be performed in a laboratory that complies with regulatory and/or accreditation requirements. (S)
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If after examination of a peripheral blood smear, it is determined that the patient will require immediate referral to another institution with expertise in the management of AL for treatment, the initial institution should, whenever possible, defer invasive procedures, including bone marrow aspiration and biopsies, to the treatment center to avoid duplicate procedures, associated patient discomfort, and additional costs. (S)
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If a patient is referred to another institution for treatment, the primary institution should provide the treatment center with all laboratory results, pathology slides, flow cytometry data, cytogenetic information, and a list of tests that are pending at the time of referral. Pending test results should be forwarded when they become available. (S)
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In the initial report, the pathologist should include laboratory, morphologic, immunophenotypic, and, if performed, cytochemical data, on which the diagnosis is based, along with a list of any pending tests. The pathologist should issue addenda/amended reports when the results of additional tests become available. (S)
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The pathologist and treating clinician should coordinate and ensure that all tests performed for classification, management, predicting prognosis, and disease monitoring are entered into the patient’s medical records. (S)
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Treating physicians and pathologists should use the current WHO terminology for the final diagnosis and classification of AL. (S)
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Recommendation Grading

Overview

Title

Initial Diagnostic Workup of Acute Leukemia

Authoring Organizations

Endorsing Organization

Publication Month/Year

February 1, 2019

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

Children and adults with acute leukemia

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Ambulatory, Hospital, Laboratory services, Outpatient, Radiology services

Intended Users

Radiology technologist, laboratory technician

Scope

Assessment and screening, Diagnosis

Diseases/Conditions (MeSH)

D015470 - Leukemia, Myeloid, Acute

Keywords

cancer, acute leukemia