ArticlesVariable Correlation Between 6-Mercaptopurine Metabolites in Erythrocytes and Hematologic Toxicity: Implications for Drug Monitoring in Children With Acute Lymphoblastic LeukemiaInnocenti, Federico* ; Danesi, Romano* ; Favre, Claudio† ; Nardi, Margherita† ; Menconi, Maria Christina† ; Di Paolo, Antonello* ; Bocci, Guido* ; Fogli, Stefano* ; Barbara, Cecilia* ; Barachini, Serena* ; Casazza, Gabriella† ; Macchia, Pierantonio† ; Tacca, Mario Del*Author Information *Division of Pharmacology and Chemotherapy, Department of Oncology, University of Pisa; †Department of Reproductive Medicine and Development, University of Pisa Received January 13, 1999; accepted February 8, 2000. Address correspondence and reprint requests to Prof. Mario Del Tacca, MD, Division of Pharmacology and Chemotherapy, Department of Oncology, University of Pisa, Via Roma 55, Pisa, PI 56126 Italy. Therapeutic Drug Monitoring: August 2000 - Volume 22 - Issue 4 - p 375-382 Buy Abstract Nineteen pediatric patients affected by acute lymphoblastic leukemia (ALL) were examined weekly with respect to 6-mercaptopurine nucleotide (6-MPN) and 6-thioguanine nucleotide (6-TGN) levels in erythrocytes during the course of maintenance treatment with 6-MP 50 mg/m2 per d and results were related to various parameters of bone marrow function to assess, in the same individual, the level of reliability of 6-MP metabolites in predicting a later change in peripheral blood cell counts. Median values for 6-MPN and 6-TGN were 57 and 200 pmol/8 × 108 erythrocytes, respectively, as measured by reversed-phase high-performance liquid chromatography (HPLC). 6-TGN levels in erythrocytes were inversely related with white blood cell count (r = −0.463, p < 0.0001, n = 361), absolute neutrophil count (r = −0.386, p < 0.0001, n = 347), erythrocyte (r = −0.354, p < 0.0001, n = 287), and platelet counts (r = −0.24, p < 0.0001, n = 319) in the majority of patients (n = 10–12), while no correlation was found for 6-MPN. In the remaining children, no evidence of correlation was demonstrated between 6-TGN levels and myelotoxicity. The results confirm the role of 6-TGN as the reference cytotoxic metabolite for evaluating the exposure to 6-MP and identifying treatment compliance in ALL children but indicate the limits of a follow-up based solely on metabolite levels and suggest that a more correct approach remains the double monitoring of 6-TGN and blood cell count with differential. © 2000 Lippincott Williams & Wilkins, Inc.