Dose adjustment strategy for high-dose methotrexate-induced toxicities in pediatric acute lymphoblastic leukemia: based on population PK analysis and exposure-toxicity relationship

Taylor ZL, Vang J, Lopez-Lopez E et al (2021) Systematic review of pharmacogenetic factors that influence high-dose methotrexate pharmacokinetics in pediatric malignancies. Cancers 13(11):2837. https://doi.org/10.3390/cancers13112837

Article  CAS  PubMed  PubMed Central  Google Scholar 

Howard SC, McCormick J, Pui CH et al (2016) Preventing and managing toxicities of high-dose methotrexate. Oncologist 21(12):1471–1482. https://doi.org/10.1634/theoncologist.2015-0164

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rask C, Albertioni F, Bentzen SM et al (1998) Clinical and pharmacokinetic risk factors for high-dose methotrexate-induced toxicity in children with acute lymphoblastic leukemia–a logistic regression analysis. Acta Oncol (Stockholm Sweden) 37(3):277–284

Article  CAS  Google Scholar 

Alsdorf WH, Karagiannis P, Langebrake C et al (2021) Standardized supportive care documentation improves safety of high-dose methotrexate treatment. Oncologist 26(2):e327–e332. https://doi.org/10.1002/onco.13603

Article  CAS  PubMed  Google Scholar 

Ramsey LB, Balis FM, O’Brien MM et al (2018) Consensus guideline for use of glucarpidase in patients with high-dose methotrexate induced acute kidney injury and delayed methotrexate clearance. Oncologist 23(1):52–61. https://doi.org/10.1634/theoncologist.2017-0243

Article  CAS  PubMed  Google Scholar 

Van der Beek JN, Oosterom N, Pieters R et al (2019) The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of paediatric ALL: a systematic review. Crit Rev Oncol Hematol 142:1–8. https://doi.org/10.1016/j.critrevonc.2019.07.003

Article  PubMed  Google Scholar 

Schmiegelow K (2009) Advances in individual prediction of methotrexate toxicity: a review. Br J Haematol 146(5):489–503. https://doi.org/10.1111/j.1365-2141.2009.07765.x

Article  CAS  PubMed  Google Scholar 

Pesenti G, Foppoli M, Manca D (2021) A minimal physiologically based pharmacokinetic model for high-dose methotrexate. Cancer Chemother Pharmacol 88(4):595–606. https://doi.org/10.1007/s00280-021-04305-2

Article  CAS  PubMed  PubMed Central  Google Scholar 

Evans WE, Relling MV, Rodman JH et al (1998) Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med 338(8):499–505. https://doi.org/10.1056/NEJM199802193380803

Article  CAS  PubMed  Google Scholar 

Foster JH, Thompson PA, Bernhardt MB et al (2019) A prospective study of a simple algorithm to individually dose high-dose methotrexate for children with leukemia at risk for methotrexate toxicities. Cancer Chemother Pharmacol 83(2):349–360. https://doi.org/10.1007/s00280-018-3733-2

Article  CAS  PubMed  Google Scholar 

Shen YQ, Wang ZJ, Wu XY et al (2022) Dose-individualization efficiently maintains sufficient exposure to methotrexate without additional toxicity in high-dose methotrexate regimens for pediatric acute lymphoblastic leukemia. Curr Med Sci 42(4):769–777. https://doi.org/10.1007/s11596-022-2589-1

Article  CAS  PubMed  Google Scholar 

Joerger M, Huitema AD, Krahenbuhl S et al (2010) Methotrexate area under the curve is an important outcome predictor in patients with primary CNS lymphoma: a pharmacokinetic-pharmacodynamic analysis from the IELSG 20 trial. Br J Cancer 102(4):673–677. https://doi.org/10.1038/sj.bjc.6605559

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kawakatsu S, Nikanjam M, Lin M et al (2019) Population pharmacokinetic analysis of high-dose methotrexate in pediatric and adult oncology patients. Cancer Chemother Pharmacol 84(6):1339–1348. https://doi.org/10.1007/s00280-019-03966-4

Article  CAS  PubMed  Google Scholar 

Hegyi M, Gulácsi A, Cságoly E et al (2012) Clinical relations of methotrexate pharmacokinetics in the treatment for pediatric osteosarcoma. J Cancer Res Clin Oncol 138(10):1697–1702

Article  CAS  PubMed  Google Scholar 

Radtke S, Zolk O, Renner B et al (2013) Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia. Blood 121(26):5145–5153. https://doi.org/10.1182/blood-2013-01-480335

Article  CAS  PubMed  Google Scholar 

Qiu KY, Xu HG, Luo XQ et al (2021) Prognostic value and outcome for ETV6/RUNX1-positive pediatric acute lymphoblastic leukemia: a report from the South China children’s leukemia group. Front Oncol 11:797194. https://doi.org/10.3389/fonc.2021.797194

Article  PubMed  PubMed Central  Google Scholar 

Group, W.H.O.M.G.R.S (2006) WHO child growth standards based on length/height, weight and age. Acta Paediatr Suppl 450:76–85. https://doi.org/10.1111/j.1651-2227.2006.tb02378.x

Article  Google Scholar 

Campagne O, Zhong B, Nair S et al (2020) Exposure-toxicity association of cyclophosphamide and its metabolites in infants and young children with primary brain tumors: implications for dosing. Clin Cancer Res 26(7):1563–1573. https://doi.org/10.1158/1078-0432.CCR-19-2685

Article  CAS  PubMed  Google Scholar 

Hospira (2019) Accessed Dec 29, Label for Methotrexate Injection. Lake Forest, IL: Hospira: Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011719s117lbl.pdf

Song Z, Hu Y, Liu S et al (2022) Medication therapy of high-dose methotrexate: an evidence-based practice guideline of the division of therapeutic drug monitoring, Chinese pharmacological society. Br J Clin Pharmacol 88(5):2456–2472. https://doi.org/10.1111/bcp.15134

Article  CAS  PubMed  Google Scholar 

O’Donoghue DF, Truong HL, Finnes HD et al (2022) High-dose methotrexate in patients with lymphoma: predictors of a complicated course. JCO Oncol Pract 18(12):e1908–e1917. https://doi.org/10.1200/OP.22.00182

Article  PubMed  Google Scholar 

Skoric B, Kuzmanovic M, Jovanovic M et al (2023) Methotrexate concentrations and associated variability factors in high dose therapy of children with acute lymphoblastic leukemia and non-hodgkin lymphoma. Pediatr Hematol Oncol 40(5):446–457. https://doi.org/10.1080/08880018.2023.2168809

Article  CAS  PubMed  Google Scholar 

Chin CK, Cheah CY (2017) How I treat patients with aggressive lymphoma at high risk of CNS relapse. Blood 130(7):867–874. https://doi.org/10.1182/blood-2017-03-737460

Article  CAS  PubMed  Google Scholar 

Kroll M, Kaupat-Bleckmann K, Morickel A et al (2020) Methotrexate-associated toxicity in children with down syndrome and acute lymphoblastic leukemia during consolidation therapy with high dose methotrexate according to ALL-BFM treatment regimen. Haematologica 105(4):1013–1020. https://doi.org/10.3324/haematol.2019.224774

Article  CAS  PubMed  PubMed Central  Google Scholar 

den Hoed MA, Lopez-Lopez E, Te Winkel ML et al (2015) Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia. Pharmacogenomics J 15(3):248–254. https://doi.org/10.1038/tpj.2014.63

Article  CAS  Google Scholar 

Oosterom N, Fiocco M, Kloos RQH et al (2020) The evaluation of red blood cell folate and methotrexate levels during protocol M in childhood acute lymphoblastic leukemia. BMC Cancer 20(1):940. https://doi.org/10.1186/s12885-020-07422-y

Article  CAS  PubMed  PubMed Central  Google Scholar 

Warren RD, Nichols AP, Bender RA (1978) Membrane transport of methotrexate in human lymphoblastoid cells. Cancer Res 38(3):668–671

CAS  PubMed  Google Scholar 

Lim AY, Gaffney K, Scott DG (2005) Methotrexate-induced pancytopenia: serious and under-reported? our experience of 25 cases in 5 years. Rheumatology (Oxford) 44(8):1051–1055. https://doi.org/10.1093/rheumatology/keh685

Article  CAS  PubMed  Google Scholar 

Locasciulli A, Mura R, Fraschini D et al (1992) High-dose methotrexate administration and acute liver damage in children treated for acute lymphoblastic leukemia. a prospective study. Haematologica 77(1):49–53

Comments (0)

No login
gif