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.
Keywords: leukopenia; methotrexate; nomogram; osteosarcoma; risk factor.