Plasma Methotrexate, Red Blood Cell Methotrexate, and Red Blood Cell Folate Values and Outcome in Children With Precursor B-acute Lymphoblastic Leukemia A Report From the Children's Oncology Group

• Authors: Wanda L. Salzer, National Cancer Institute; Naomi J. Winick, University of Texas Southwestern; Pierre Wacker, University Hospital of Geneva; Xiaomin Lu, University of Florida; Meenakshi Devidas, University of Florida; Jonathan J. Shuster, University of Florida; Donald H. Mahoney, Baylor College of Medicine; Stephen Lauer, Emory University; Bruce M. Camitta, Medical College of Wisconsin
• Journal Title: Journal of Pediatric Hematology/Oncology
• Volume: Volume 34, Number 1
• Publisher: Lippincott, Williams & Wilkins | 2012-01-01, Pages E1-E7
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/MPH.0b013e31820ee239
• Subjects: Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Health Sciences, Pharmacology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Hematology; Pediatrics; red blood cell methotrexate and folate; childhood acute lymphoblastic leukemia; methotrexate metabolism; red blood cell; HIGH-DOSE METHOTREXATE; ACUTE LYMPHOCYTIC-LEUKEMIA; INTRAVENOUS METHOTREXATE; THERAPY; RISK; PHARMACOKINETICS; LEUCOVORIN; PHARMACODYNAMICS; MERCAPTOPURINE; IDENTIFICATION

Abstract

Plasma steady state methotrexate (MTX) level and red blood cell (RBC) MTX and folate concentrations were evaluated in 1124 children with newly diagnosed acute lymphoblastic leukemia enrolled in the Pediatric Oncology Group studies 9005 (lower risk; Regimens A and C) and 9006 (higher risk; Regimen A). These regimens included intermediate-dose MTX (1 g/m) given as a 24 hours infusion every other week for 12 doses during intensification. Plasma MTX level was evaluated at the end of MTX infusions. RBC MTX and folate concentrations were measured at the end of intensification. The 5 year continuous complete remission was 76±1.4% versus 85±3.0% for those patients with steady state MTX levels less than or equal to and greater than 14 μM, respectively (P=0.0125). Hispanic children had significantly reduced median steady state MTX levels, 8.7 μM, compared with non-Hispanic children, 9.95 μM (P=0.0015), but this did not correlate with a difference in outcome. Neither RBC MTX, RBC folate, nor the RBC MTX:folate ratio identified children at increased risk of failure.