Research Paper Volume 14, Issue 12 pp 5023—5033

Nomogram predicting leukopenia in osteosarcoma after high-dose methotrexate chemotherapy

Haixiao Wu1,2, *, , Guijun Xu2,3, *, , Zhijun Li1,2, *, , Yao Xu1,2, , Yile Lin2,5, , Vladimir P. Chekhonin2,6, , Karl Peltzer2,7, , Jun Wang8, , Shu Li2,9, , Huiyang Li2, , Jin Zhang1,2, , Yuan Xue2,5, , Wenjuan Ma1,2, , Xin Wang2,4, , Chao Zhang1,2, ,

  • 1 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
  • 2 The Sino-Russian Joint Research Center for Bone Metastasis in Malignant Tumor, Tianjin, China
  • 3 Department of Orthopedics, Tianjin Hospital, Tianjin University, Tianjin, China
  • 4 Department of Health Management Center (Epidemiology and Biostatistics), First Affiliated Hospital, Army Medical University, Chongqing, China
  • 5 Department of Orthopaedic Surgery, Tianjin Medical University General Hospital, Tianjin, China
  • 6 Department of Basic and Applied Neurobiology, Federal Medical Research Center for Psychiatry and Narcology, Moscow, Russian Federation
  • 7 Department of Psychology, University of the Free State, Turfloop, South Africa
  • 8 Department of Oncology, Radiology and Nuclear Medicine, Medical Institute of Peoples' Friendship University of Russia, Moscow, Russian Federation
  • 9 School of Management, Tianjin University of Traditional Chinese Medicine, Tianjin, China
* Equal contribution

Received: November 1, 2021       Accepted: April 22, 2022       Published: May 31, 2022
How to Cite

Copyright: © 2022 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Purpose: To explore the trends of plasma drug concentration changes after high-dose methotrexate (MTX) treatment of osteosarcoma (OS), analyse the risk factors for leukopenia (LP) after MTX treatment, and establish a LP prediction nomogram.

Methods: A total of 35 OS patients at Tianjin Medical University Cancer Institute and Hospital between 2017 and 2021 were collected (the construction cohort). Another 12 OS patients between 2019 and 2021 in P.A. Hertsen Moscow Oncology Research Center were involved (the external validation cohort). Peripheral venous blood MTX concentration (CMTX) was monitored at 0h, 6h, 24h, 48h and 72h after MTX administration. The characteristics were collected: age, sex, body surface area, lesion site, pathological subtype, pathological fractures, American Joint Committee on Cancer (AJCC) clinical stage, MTX dose, tumour necrosis, Ki-67 index, erythrocyte count, haemoglobin count, white blood cell count, platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, albumin concentration, creatinine, alkaline phosphatase, and lactate dehydrogenase. Logistic regression analysis was used to determine the risk factors for LP occurrence. Significant factors were used to construct the prediction nomogram.

Results: A total of 128 MTX chemotherapy cycles from 35 OS patients were included. Female, Ki-67>20%, CMTX>112μmol/L at 6h, PLT, and AST were risk factors for post-chemotherapy LP occurrence. The LP prediction nomogram was created and validated.

Conclusions: Female, CMTX at 6h, Ki-67 index, AST and PLT before MTX treatment were risk factors for LP in OS patients who received MTX treatment. The established nomogram can guide personalized LP prediction in OS patients receiving MTX chemotherapy.


MTX: methotrexate; OS: osteosarcoma; LP: leukopenia; CMTX: methotrexate concentration; WBC: white blood cell; PLT: platelet count; ALT: alanine aminotransferase; AST: aspartate aminotransferase; LDH: lactate dehydrogenase; NCCN: National Comprehensive Cancer Network; AJCC: American Joint Committee on Cancer.