What are the typical laboratory findings in leukemia, including complete blood count, peripheral smear, and related studies?

Laboratory Findings in Leukemia

Laboratory findings in leukemia vary dramatically by subtype, but the complete blood count (CBC) with differential and peripheral blood smear examination form the cornerstone of initial diagnosis, with specific patterns distinguishing acute from chronic forms and myeloid from lymphoid lineages. 1

Chronic Lymphocytic Leukemia (CLL)

Complete Blood Count

• Sustained absolute lymphocytosis ≥5,000/μL (5 × 10⁹/L) for at least 3 months is the diagnostic hallmark, with clonality confirmed by flow cytometry 2
• Anemia (hemoglobin <10.0 g/dL by Binet criteria or <11.0 g/dL by Rai criteria) develops with disease progression and indicates advanced stage 2, 1
• Thrombocytopenia (platelets <100 × 10⁹/L) signifies Binet stage C or Rai stage IV disease 2, 1

Peripheral Blood Smear

• Small, mature-appearing lymphocytes with narrow cytoplasmic borders and dense nuclei lacking discernible nucleoli predominate 2
• Partially aggregated chromatin is characteristic 2
• Smudge cells (Gumprecht shadows) are commonly seen but not specific 3

Flow Cytometry (Essential for Diagnosis)

• Co-expression of CD5 antigen with B-cell markers CD19, CD20, and CD23 is pathognomonic 2
• Characteristically low levels of surface immunoglobulin, CD20, and CD79b compared to normal B cells 2
• Monoclonal restriction to either κ or λ light chains 2

Additional Laboratory Studies

• Serum chemistry including lactate dehydrogenase (LDH), bilirubin, and serum immunoglobulin levels 2
• Direct antiglobulin test (DAT) to assess for autoimmune hemolytic anemia 2
• FISH analysis for del(17p) and del(11q) prior to therapy initiation 2

Acute Myeloid Leukemia (AML)

Complete Blood Count

• Leukocytosis with circulating blasts is common, though white blood cell counts are highly variable 1
• Anemia (hemoglobin <11.0 g/dL) is present in most cases 1
• Thrombocytopenia (platelets <100,000/μL) occurs in the majority of patients 1
• Neutropenia may paradoxically exist despite elevated total WBC due to blast replacement 1

Peripheral Blood Smear

• Peripheral blood blasts are typically visible, with percentage varying by disease burden 1
• Auer rods in blasts are pathognomonic for AML when present 1
• Absolute neutrophil count is often decreased despite high total WBC 1

Bone Marrow Examination

• ≥30% blasts in bone marrow aspirate establishes the diagnosis (traditional criteria) 4
• Bone marrow is the preferred specimen, though peripheral blood can be used when circulating blast percentage exceeds analytical sensitivity 2
• Morphology, cytochemistry, immunophenotyping, and cytogenetics are all essential 2, 5

Cytogenetic and Molecular Studies

• Conventional karyotyping should be performed on all diagnostic specimens 2, 4
• FISH panel typically includes: RUNX1::RUNX1T1 for t(8;21), CBFB rearrangement for inv(16)/t(16;16), KMT2A rearrangement, -5/5q-, -7/7q-, and TP53 deletion 2
• Molecular testing for NPM1 mutations and other prognostic markers 5

Chronic Myeloid Leukemia (CML)

Complete Blood Count

• Marked leukocytosis with high differentiated granulocyte counts is characteristic 1
• Normal or elevated platelet counts distinguish CML from acute leukemias 1
• Mild anemia is common 1

Peripheral Blood Smear

• "Pathological left shift" showing the full spectrum of granulocytic precursor cells 1
• Basophilia may be present; ≥20% basophils indicates accelerated phase 1
• Blasts <10% in chronic phase; 10-19% indicates accelerated phase; ≥20-30% defines blast phase 1

Diagnostic Molecular Testing

• BCR-ABL1 fusion gene testing is mandatory to confirm diagnosis 2, 6
• Thrombocytopenia (<100,000/μL) unrelated to therapy suggests accelerated phase 1

Screening Parameters

• Absolute basophil count >0.43 × 10⁹/L has the highest specificity (AUC 0.982) for CML screening 7
• Immature granulocyte count >0.46 × 10⁹/L is also highly sensitive (AUC 0.975) 7

Plasma Cell Leukemia (PCL)

Diagnostic Criteria

• ≥20% circulating plasma cells in peripheral blood and/or absolute plasma cell count >2 × 10⁹/L 2
• Lower thresholds (≥5% plasma cells or absolute count ≥0.5 × 10⁹/L) should be recorded for prospective analysis 2
• Careful morphological examination of peripheral blood smears by experienced hematologists is essential 2

Additional Laboratory Findings

• Leukocytosis and elevated LDH suggest PCL 2
• Complete hemogram with renal/hepatic function, calcium, quantitative immunoglobulins, and serum free light chains 2
• Flow cytometry showing CD38+/CD138+ plasma cells with higher CD20 and lower CD56 expression compared to multiple myeloma 2

Chronic Myelomonocytic Leukemia (CMML)

Diagnostic Laboratory Criteria

• Persistent peripheral blood monocytosis >1 × 10⁹/L 2, 6
• Bone marrow blasts <20% 2
• Absence of BCR-ABL1 fusion gene and PDGFRA/PDGFRB rearrangements 2, 6

Peripheral Blood Findings

• Dysgranulopoiesis including nuclear hypolobation (pseudo-Pelger-Huët) and cytoplasmic hypogranulation 6
• Presence of promonocytes and immature neutrophil precursors 2, 6

Bone Marrow Examination

• Granulocytic hyperplasia with dysplasia in one or more myeloid lineages 2
• Blast count includes myeloblasts, monoblasts, and promonocytes 2

Cytogenetics and Molecular Testing

• Most frequent abnormalities: chromosome 7 lesions, trisomy 8, complex karyotype 2, 6
• Molecular mutations in TET2, SRSF2, ASXL1, and RAS genes; 93% of CMML patients carry at least one somatic mutation 2, 6

Critical Diagnostic Principles

Nonspecific CBC findings always require bone marrow examination or peripheral blood flow cytometry for definitive leukemia diagnosis 1. Immunophenotyping, cytogenetics, and molecular studies are essential to distinguish leukemia subtypes and guide therapy 2, 1, 5.

Common Pitfalls to Avoid

• Never rely on relative percentages alone—always calculate absolute counts (e.g., absolute lymphocyte count, absolute monocyte count) 6
• Do not use peripheral blood for cytogenetics in acute lymphoblastic leukemia—41% of ALL cases have insufficient PB metaphases compared to 17% in AML 8
• Failure to perform BCR-ABL1 testing can miss chronic myeloid leukemia 2, 6
• The absolute lymphocyte count alone should never trigger treatment in CLL regardless of elevation 1