What is the initial blood evaluation for suspected leukemia?

Initial Blood Evaluation for Suspected Leukemia

The initial blood evaluation for suspected leukemia must include a complete blood count (CBC) with peripheral blood differential and smear review, followed immediately by comprehensive metabolic panel, lactate dehydrogenase, uric acid, phosphate levels, and coagulation studies if acute promyelocytic leukemia is suspected. 1

Essential Initial Laboratory Tests

Peripheral Blood Studies

• CBC with differential count and manual peripheral blood smear review is the foundational test, examining for leukocytosis, cytopenias, and circulating blasts 1, 2
• Comprehensive metabolic panel must be obtained to assess for tumor lysis syndrome, particularly critical in patients with B-lymphoblastic lymphoma 1
• Lactate dehydrogenase, uric acid, and phosphate levels are essential markers of tumor burden and tumor lysis syndrome risk 1
• Coagulation panel (prothrombin time, partial thromboplastin time, fibrinogen) is mandatory when acute promyelocytic leukemia is suspected to detect early disseminated intravascular coagulation 1

Advanced Peripheral Blood Testing (When Sufficient Blasts Present)

If peripheral blood shows adequate blasts (≥30% of nucleated cells), the following can be performed on blood alone, potentially avoiding immediate bone marrow biopsy in unstable patients:

• Multicolor flow cytometry immunophenotyping to distinguish B-ALL, T-ALL, AML, or mixed phenotype acute leukemia 1, 2
• Manual differential count and morphologic review for blast characterization 1
• Fluorescent in situ hybridization (FISH) for critical cytogenetic abnormalities 1, 2
• Molecular studies (PCR, next-generation sequencing) for prognostic mutations 1, 2

Critical caveat: While peripheral blood can provide diagnostic information when blasts are abundant, cytogenetic analysis from peripheral blood is insufficient in 23% of cases (41% in acute lymphoblastic leukemia, 17% in acute myeloid leukemia), making bone marrow aspiration ultimately necessary for complete evaluation 3

Bone Marrow Evaluation (Definitive Diagnosis)

Bone marrow aspiration and core biopsy remain the gold standard and should be performed unless clinically contraindicated 1, 2:

• Morphologic examination of aspirate, touch imprints, cell clots, and core biopsy with manual blast enumeration (≥30% blasts required for diagnosis) 2
• Multicolor comprehensive flow cytometry on bone marrow aspirate for immunophenotyping 1, 2
• Conventional karyotyping (must be performed on bone marrow, not peripheral blood) 1, 2
• FISH studies tailored to suspected leukemia subtype 1, 2
• Molecular genetic testing (PCR, RT-PCR, next-generation sequencing) for prognostic markers and targetable mutations 1, 2

If bone marrow aspirate yields a "dry tap," perform cell count and morphology review on touch imprint preparations 1

Subtype-Specific Testing Priorities

For Suspected Acute Myeloid Leukemia

• Rapid FISH for PML-RARA if acute promyelocytic leukemia suspected (medical emergency) 1
• FLT3-ITD mutation testing (strong recommendation for all AML) 1
• Molecular panel: IDH1, IDH2, TET2, WT1, DNMT3A, TP53, NPM1, CEBPA 1
• KIT mutation for core binding factor AML (adults: strong recommendation; pediatrics: may perform) 1

For Suspected Acute Lymphoblastic Leukemia (Adult)

• BCR-ABL1/t(9;22) testing (strong recommendation—Philadelphia chromosome) 1
• KMT2A (MLL) translocation testing (recommendation) 1
• Mutational analysis: PAX5, JAK1, JAK2, IKZF1 for B-ALL; NOTCH1, FBXW7 for T-ALL 1, 2

For Suspected Acute Lymphoblastic Leukemia (Pediatric)

• ETV6-RUNX1/t(12;21), BCR-ABL1/t(9;22), KMT2A translocation, iAMP21, trisomy 4 and 10 (strong recommendation) 1, 2

Additional Baseline Studies

• Imaging: Chest x-ray to assess for infection; CT or ultrasound of abdomen for organomegaly and lymphadenopathy (particularly if mediastinal mass, hepatosplenomegaly, or lymphadenopathy present) 1
• Hepatitis serology if anti-CD20 monoclonal antibody therapy planned 1
• Renal function assessment if nucleoside analog therapy anticipated 1

Common Pitfalls to Avoid

• Do not delay coagulation studies when acute promyelocytic leukemia is in the differential—disseminated intravascular coagulation can be rapidly fatal 1
• Do not rely solely on peripheral blood for cytogenetics—nearly one-quarter of cases will have insufficient metaphases from blood samples 3
• Do not skip comprehensive metabolic panel and tumor lysis markers—these patients can rapidly develop life-threatening metabolic derangements 1
• Ensure flow cytometry and molecular characterization are comprehensive enough for subsequent minimal residual disease monitoring—this must be planned from initial diagnosis 1
• Document ethnicity/race—Hispanics have worse outcomes in ALL and higher incidence of Philadelphia-like ALL 1
• Document environmental/occupational exposures (benzene, formaldehyde, butadiene, ionizing radiation) as potential risk factors 1