Leukocyte Alkaline Phosphatase in Leukemoid Reaction Diagnosis
Leukocyte alkaline phosphatase (LAP) is significantly elevated in leukemoid reactions and serves as a key diagnostic tool to distinguish leukemoid reactions from chronic myeloid leukemia (CML), where LAP is characteristically low or absent.
Diagnostic Utility
LAP scoring provides critical discrimination between reactive and malignant leukocytosis, particularly when extreme neutrophilia creates diagnostic uncertainty 1, 2. The test exploits a fundamental biological difference:
- Leukemoid reactions: LAP is markedly elevated, often with scores ranging from 3.84-47.24 (×10⁻⁵ mV·s/cell) with median values around 9.58 1
- Chronic myeloid leukemia: LAP is characteristically decreased, with scores ranging from 0.07-1.75 (×10⁻⁵ mV·s/cell) and median of 0.79 1
- Normal range: LAP slopes between 0.61-8.49 (×10⁻⁵ mV·s/cell) with median 2.04 1
Clinical Application Algorithm
When encountering extreme neutrophilia (particularly WBC >100,000/mcL), follow this approach:
- Obtain LAP score immediately if distinguishing between leukemoid reaction and CML 2
- Elevated LAP confirms leukemoid reaction and helps avoid unnecessary bone marrow biopsy and cytogenetic testing in unequivocal cases 3
- Low LAP suggests CML and mandates cytogenetic confirmation with t(9;22) and BCR-ABL1 testing 4, 1
Important Caveats
LAP has significant limitations that must be recognized:
- Analytical uncertainty is substantial, with coefficient of variation exceeding 100% at low scores and approximately 20% at high scores 3
- Serial LAP determinations are unreliable for detecting score changes, as analytical "noise" exceeds diagnostic signal 3
- LAP may not distinguish chronic neutrophilic leukemia from leukemoid reaction, as both can show elevated values 5
- A suitably high diagnostic decision threshold is essential to eliminate false negatives, though this strategy may require up to half of tested patients to undergo further workup 3
Modern Context
Current diagnostic guidelines for CML do not include LAP as a mandatory test 4. The 2017 ESMO guidelines emphasize that CML diagnosis must be confirmed by cytogenetics showing t(9;22)(q34;q11) and multiplex RT-PCR showing BCR-ABL1 transcripts, with no mention of LAP 4. This reflects the superior specificity and reliability of molecular diagnostics over LAP scoring.
LAP remains most useful in resource-limited settings or when rapid bedside differentiation is needed before molecular results are available 1. In cases of drug or toxin exposure causing extreme neutrophilia, an elevated LAP helps confirm leukemoid reaction and avoid unnecessary invasive procedures 2.