Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jul 5:11:6265-6274.
doi: 10.2147/CMAR.S207959. eCollection 2019.

Identifying risk factors for high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia

Xiao Li  1 , Zhongguo Sui  1 , Fanbo Jing  1 , Wen Xu  1 , Xiangpeng Li  1 , Qie Guo  1 , Shuhong Sun  1 , Xiaolin Bi  2
Affiliations

Identifying risk factors for high-dose methotrexate-induced toxicities in children with acute lymphoblastic leukemia

Xiao Li et al. Cancer Manag Res. .

Abstract

Background: Whether monitoring of the methotrexate (MTX) concentrations after high-dose MTX (HD-MTX) infusion can predict toxicities is still controversial, especially when HD-MTX therapy is used in the treatment of children with acute lymphoblastic leukemia (ALL), which is different than the previous schedules. The relationship between patient characteristics and severe adverse events (AEs) has yet to be determined.

Objective: To analyze the relationship between the MTX concentration and toxicities and to identify the risk predictors from patient characteristics for severe AEs during HD-MTX therapy in children with ALL.

Methods: We conducted a retrospective study on children with ALL who were treated with 388 HD-MTX infusions. The chi-square test and univariate and logistic regression analyses were used to analyze the relationship between the MTX concentrations and toxicities and to identify predictors for severe AEs.

Results: Febrile neutropenia (P=0.000) and vomiting (P=0.034) were more likely to occur if the infusion had an MTX level ≥1 μmol/L at 44 h, but other toxicities had no correlations with MTX concentration. Predictive factors for toxicities were as follows: higher risk stratification and higher values of albumin (ALB) for leucopenia, higher values of white blood cell count (WBC) for anemia, higher values of ALB and creatinine (Cr) for neutropenia, higher risk stratification and higher 44-h MTX concentration for febrile neutropenia, higher values of alanine transferase (ALT) for elevated ALT, higher values of ALT for elevated aspartate transferase (AST), and higher values of total bilirubin (TBil) for vomiting.

Conclusion: Routine monitoring of 44-h MTX concentrations is essential to identify patients at high risk of developing febrile neutropenia and vomiting. This study may provide a reference for clinicians to distinguish patients with a relatively high risk of severe AEs based on certain characteristics before HD-MTX infusion.

Keywords: acute lymphoblastic leukemia; high-dose methotrexate; methotrexate concentration; patient characteristics; risk predictors; toxicities.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The 44-h plasma MTX concentrations in all 388 infusions. Abbreviation: MTX, methotrexate.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Xing C, Liang B, Wu J, et al. Prognostic significance of leukopenia during the induction phase in adult B cell acute lymphoblastic leukemia. Cancer Manag Res. 2018;10:625–635. doi:10.2147/CMAR.S158359 - DOI - PMC - PubMed
    1. May J, Carson KR, Butler S, Liu W, Bartlett NL, Wagner-Johnston ND. High incidence of methotrexate associated renal toxicity in patients with lymphoma: a retrospective analysis. Leuk Lymphoma. 2014;55(6):1345–1349. doi:10.3109/10428194.2013.840780 - DOI - PMC - PubMed
    1. Cheng KK. Association of plasma methotrexate, neutropenia, hepatic dysfunction, nausea/vomiting and oral mucositis in children with cancer. Eur J Cancer Care (Engl). 2008;17(3):306–311. doi:10.1111/j.1365-2354.2007.00843.x - DOI - PubMed
    1. Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med. 1998;338(8):499–505. doi:10.1056/NEJM199802193380803 - DOI - PubMed
    1. Abromowitch M, Ochs J, Pui CH, et al. High-dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: st. Jude total therapy study X. Med Pediatr Oncol. 1988;16(5):297–303. - PubMed