Diagnostic discrimination and cost effective assay strategy for leukocyte alkaline phosphatase.

Decreased leukocyte alkaline phosphatase (LAP) is a first line test for chronic myelogenous leukemia (CML), generally preceding a diagnostic algorithm which also includes bone marrow biopsy, cytogenetic analysis, and molecular diagnostics. We found the analytical uncertainty of LAP assays to range from over 100% coefficient of variation at low scores to about 20% at high scores. However, the receiver-operator characteristics derived from LAP determinations in 50 consecutive cases suggest that a suitably high diagnostic decision threshold still can eliminate false negatives. As a consequence of such a strategy, as many as half the tested patients, classified unequivocally as the negatives, can avoid further invasive and costly workup. On the other hand, serial LAP determinations, whether performed to detect change to a lower or to a higher score, are unlikely to produce conclusive diagnostic signals exceeding analytical 'noise.'