Efficacy and association analysis of high‑dose methotrexate in the treatment of children with acute lymphoblastic leukemia

Gong, Fangwei; Meng, Qing‐Jun; Liu, Chengjuan; Zhao, Yeqi

doi:10.3892/ol.2019.10128

Cited by 4 publications

(7 citation statements)

References 26 publications

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“…A deep analysis of efficacy of HDMTX application in the treatment of children with ALL is presented in the paper of Gong et al [177]. Children with ALL were divided into smaller subgroups according to the subtype of the disease (B-or T-lineage ALL) and disease course.…”

Section: Content Of Combination Regimens Type Of Cancer Referencementioning

confidence: 99%

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

Koźmiński

Halik

Chesori

et al. 2020

IJMS

206

120

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Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer’s disease or myasthenia gravis will be discussed.

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Section: Content Of Combination Regimens Type Of Cancer Referencementioning

confidence: 99%

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

Koźmiński

Halik

Chesori

et al. 2020

IJMS

206

120

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“…The LLOQ for MTX was determined to be 0.09 μM/L according to the clinical requirement with accuracy and precision (►Fig. 4 and ►Table 4).…”

Section: Linearity and Lower Limit Of Quantificationmentioning

confidence: 99%

A Rapid Method for Determination of Serum Methotrexate Using Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry and Its Application in Therapeutic Drug Monitoring

et al. 2023

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Objectives Methotrexate (MTX) has anticancer therapeutic potential with multiple doses-related adverse effects and toxicities. Immunoassays for therapeutic monitoring of serum MTX have their own limitations. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is considered as the reference method; however, commercially availability of them is limited. We aimed to adapt/develop an in-house LC-MS/MS method for therapeutic monitoring of serum MTX. Materials and Methods Serum protein precipitation was performed using acetonitrile–water containing 250 μM solution of aminoacetophenone as internal standard (IS). Chromatographic separation was achieved on a C18 column with mobile phase of 0.1% solution of formic acid (solvent A) and acetonitrile (solvent B) at a flow rate of 0.4 mL/min. MS was performed under positive ion mode with mass transition for MTX and IS as m/z 455.1→308.1 and 136.2→94.1, respectively. The method was validated by following Bioanalytical Method Validation Guidance for Industry, 2018 and applied on leukemia patients' samples on MTX therapy. Results The correlation coefficient of eight serially diluted calibration standards of 0.09 to 12.5 μM was >0.99 and had linearity with > 95% precision and accuracy at analytical quality control levels. The lower limit of MTX quantification achieved was 0.09 μM with good intensity and sharp peak as compared with blank sample. The total run time of the assay was 5 minutes. The serum MTX levels obtained by this method in leukemia patients exhibited clinical correlation and an excellent agreement with commercial immunoassay used in parallel. Conclusion We were able to develop a rapid, sensitive, and cost-effective LC-MS/MS method suitable for therapeutic drug monitoring of MTX in routine clinical diagnostic laboratories.

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“…Other toxicities after high-dose methotrexate include high-grade myelosuppression in 5%-10% of patients (33,49,51,69,80,84,98,99) with a nadir at 2 weeks (52), hepatotoxicity in 8%-30% of patients (33,77,80,84,90,100-102), and mucositis in 10%-30% of patients (33,37,49,51,53,56,59,68,77,82,84,86,99,(101)(102)(103)(104)(105). In modern cohorts, inpatient mortality related to high-dose methotrexate is uncommon, but increases to approximately 4%-12% in those that develop AKI (58,71,73,85).…”

Section: Overview Of Methotrexate Toxicitymentioning

confidence: 99%

Extracorporeal Treatment for Methotrexate Poisoning

Ghannoum

Roberts

Goldfarb

et al. 2022

CJASN

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Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

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Efficacy and association analysis of high‑dose methotrexate in the treatment of children with acute lymphoblastic leukemia

Cited by 4 publications

References 26 publications

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

A Rapid Method for Determination of Serum Methotrexate Using Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry and Its Application in Therapeutic Drug Monitoring

Extracorporeal Treatment for Methotrexate Poisoning

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