Dosage of oral methotrexate/6-mercaptopurine in the maintenance treatment of childhood acute lymphoblastic leukemia: a single-center experience

DOI
  • Utano Tomoyuki
    Department of Pediatrics, St. Luke’s International Hospital Department of Practical Pharmacy, Keio University
  • Tanaka Yoichi
    Department of Practical Pharmacy, Center for Clinical Pharmacy and Sciences, Kitasato University
  • Kizu Junko
    Department of Practical Pharmacy, Keio University
  • Kamiya Takahiro
    Department of Pediatrics, St. Luke’s International Hospital
  • Ogawa Chitose
    Department of Pediatrics, St. Luke’s International Hospital
  • Ishida Yasushi
    Department of Pediatrics, St. Luke’s International Hospital
  • Hosoya Ryota
    Department of Pediatrics, St. Luke’s International Hospital
  • Manabe Atsushi
    Department of Pediatrics, St. Luke’s International Hospital

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Other Title
  • 小児急性リンパ性白血病の維持療法期間におけるメルカプトプリン及びメトトレキサート投与量の推移
  • ～単施設における検討～

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Background. Mercaptopurine (6-MP) and methotrexate (MTX) form the backbone of maintenance therapy for childhood acute lymphoblastic leukemia (ALL). It is widely noted that the inter- and intrapatient variations in the clinical efficacy and adverse effects of 6-MP and MTX are enormous, and optimal dosage varies considerably. The aim of this study was to elucidate the factors that affect the optimal dosage setting of 6-MP/MTX in the maintenance phase of treatment. Methods. Fifty children (aged 1 to 15) who were diagnosed as having ALL in our institution between April 1995 to March 2010 and who finished maintenance therapy were enrolled in this study. We investigated the 6-MP/MTX dosages from the beginning (6-MP/MTX: 40 mg/m2 / 25 mg/m2) and compared patients’ characteristics (sex, white blood cell count, age, immunophenotype, body surface area, prednisolone response, risk classification, obesity index) and relapse rates across each category. Results. Thirty-four patients needed to change their 6-MP dosage (increase, n=20; decrease, n=14), whereas 18 patients needed to change their MTX dosage (increase, n=3; decrease, n=15). The patients’ characteristics were not significantly different in each category of dosage changes; on the other hand, it was shown that 4 of 7 relapse patients experienced an increase in 6-MP dosage of more than 50% within the first 6 months after the start of maintenance treatment. Conclusions. In this study, we conclude that the patients’ characteristics are not related to the 6-MP/MTX dosage change in maintenance therapy, and it is suggested that the major increase in 6-MP dosage may predict the occurrence of relapse.

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