Title Page

The effect of the plasma methotrexate concentration during high-dose methotrexate therapy on prognosis of childhood acute lymphoblastic leukemia

Running title: Methotrexate concentration and prognosis

Chan Liao, Xiao-Jun Xu, Jing-Ying Zhang, Hua Song, Wei-Qun Xu, He-Ping Shen, Di-Ying Shen, Fen-Ying Zhao, Juan Liang, Yong-Min Tang*.

Department of Pediatric Hematology-Oncology, The Children’s Hospital, Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health. #57 Zhuganxiang Road, Yan-an Street, Hangzhou, China.

* Corresponding author: E-mail: y_m_tang@zju.edu.cn. Tel: +86 571 88873450; Fax: +86 571 87033296.

Principal Investigator statement: The authors confirm that the Principal Investigator for this paper is Chan Liao and that she had direct clinical responsibility for patients.

Keywords: methotrexate, pharmacokinetics, pharmacogenomics, childhood, survival, acute lymphoblastic leukemia