Elevated Alkaline Phosphatase in a Cancer Patient: Think You Know the Source?

A 45-year-old male with recurrent metastatic Ewing sarcoma presented to Memorial Sloan Kettering Cancer Center for potential enrollment in a clinical trial. Initial laboratory results were notable for increased alkaline phosphatase levels [(ALP2, 495 U/L; (reference interval: 33–97 U/L); Abbott Architect C8000] and γ-glutamyl transferase levels [GGT, 393 U/L (reference interval: 0–73 U/L); Abbott Architect C8000] but were otherwise unremarkable, including normal levels of aspartate aminotransferase (AST) and alanine transaminase (ALT). Elevations in ALP and GGT levels suggested liver disease, although the patient had no previous history of liver abnormalities. Given the patientu0027s history of metastatic bone disease, it was suspected that the observed elevation in ALP was due to increased bone ALP isoenzyme. However, it was important to document the origin of the increased ALP as the patient was to be enrolled in an investigational trial that would define drug dosage and side effects. Elevations in ALP over the course of the trial that were attributable to liver-specific isoenzymes would be reported as a dose-limiting toxicity and could delay treatment or potentially exclude the patient from the clinical trial. Conversely, elevations in ALP originating from bone and secondary to disease would not be reported as toxicity.The laboratory was consulted regarding testing options to identify the specific isoenzyme(s) responsible …