Diabetes is a risk factor for high-dose methotrexate-associated AKI in lymphoma patients

Wang, Yujia; Li, Wei; Guan, Yi; Wang, Qian; Xie, Qionghong; Hao, Chuan‐Ming

doi:10.1080/0886022x.2020.1838926

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…After the establishment of LV rescue treatment, the incidence of HD-MTX-related deaths has reportedly improved from 6% to 0.08%. 6,7 Recently, a new HD-MTX protocol including support by the entire treatment team (nurse/pharmacist/physician) has been reported. 8 Despite these approaches, delayed elimination of MTX from the plasma, which can cause severe adverse effects such as acute renal failure, gastrointestinal toxicities, and myelosuppression, has been observed in some cases.…”

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confidence: 99%

Low Serum Albumin Level Is a Risk Factor for Delayed Methotrexate Elimination in High-Dose Methotrexate Treatment

et al. 2021

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Background In high-dose methotrexate (HD-MTX) therapy, delayed elimination of MTX from plasma leads to severe adverse effects. However, the risk factors for the delayed elimination of plasma MTX are still unclear. Objective The purpose of this study was to investigate the factors related to the delayed MTX elimination in HD-MTX monotherapy. Methods This retrospective study was performed on patients who received HD-MTX monotherapy between April 2009 and March 2019 at the Hiroshima University Hospital. Patients were divided into a “Normal” and a “Delayed” group according to their MTX plasma concentration at 48 or 72 hours after administration. Patient characteristics, dose of HD-MTX, MTX plasma concentration, and adverse effects were analyzed and compared between the 2 groups. Results A total of 74 patients were included in this study. Logistic analysis of patient baseline characteristics was performed to identify risk factors for delayed MTX elimination. Serum albumin (ALB) was detected as a risk factor. Univariate and multivariate analysis revealed that low ALB level (<3.7 g/dL) and type of cancer were associated with delayed MTX elimination (univariate analysis: odds ratio [OR] = 6.00, P = 0.004, and OR = 4.33, P = 0.039, respectively; multivariate analysis: adjusted OR [AOR] = 6.45, P = 0.006, and AOR = 8.11, P = 0.018, respectively). Adverse effects were not significantly different between the 2 groups, excluding renal impairment. Conclusions and Relevance Our study showed that low ALB is a risk factor for delayed MTX elimination in HD-MTX monotherapy. Pharmacokinetic analysis is needed to establish the dose of HD-MTX in patients with a low ALB level.

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confidence: 99%

Low Serum Albumin Level Is a Risk Factor for Delayed Methotrexate Elimination in High-Dose Methotrexate Treatment

et al. 2021

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“…In addition, we did not find that diabetes was associated with MTX‐induced toxicities, such as AKI. Previous studies have shown that type 2 diabetes is a risk factor for HD‐MTX‐associated AKI because patients with type 2 diabetes had lower urine pH values which contributed to MTX elimination delay and therefore AKI occurrence 19 . In our study, all patients were fully hydrated during treatment, and their urine was alkalized to pH > 7 before chemotherapy, which reduced the variation in patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 59%

“…Previous studies have shown that type 2 diabetes is a risk factor for HD-MTX-associated AKI because patients with type 2 diabetes had lower urine pH values which contributed to MTX elimination delay and therefore AKI occurrence. 19 In our study, all patients were fully hydrated during treatment, and their urine was alkalized to pH > 7 before chemotherapy, which reduced the variation in patients with type 2 diabetes. In addition, we also found that baseline values of ALT, Hb, WBC and NEUT were related to lower MTX clearance and thus higher concentrations of MTX (Table 5); However, considering that the patients enrolled in this study almost had normal baseline values, we could not use them as a biomarker for the toxicities induced by MTX.…”

Section: Discussionmentioning

confidence: 84%

Risk factors for high‐dose methotrexate associated toxicities in patients with primary central nervous system lymphoma

Sun

Tao

Ding

et al. 2022

Clinical Pharmacy Therapeu

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What is Known and Objective Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study aimed to explore the factors influencing major adverse events in patients with primary central nervous system lymphoma treated with high‐dose MTX (HD‐MTX), which could be useful in clinical practice. Methods Fifty‐four patients who received 175 courses of MTX at 3–8 g/m2 between January 2015 and December 2016 were enrolled in this study. We assessed the association between clinical characteristics, MTX pharmacokinetics, MTX delayed elimination, and adverse events, including hepatotoxicity, acute kidney injury (AKI), and myelosuppression. Results and Discussion A total of 124 adverse events occurred after MTX infusion. Using independent sample t‐tests, we found that patients with myelosuppression had higher MTX area under the concentration‐time curve up to 48 h after infusion (AUC0‐48h) (p = 0.001) and MTX peak concentration (Cmax) (p = 0.002). MTX concentrations at 48 and 72 h were higher in patients with AKI than in those without (p = 0.034 and p = 0.041, respectively). Using chi‐square tests, we found that AKI was correlated with MTX elimination at either 48 h or 72 h (22.1% vs. 8.2%, p = 0.010). By multivariate logistic regression model, our results showed that baseline level of ALT and WBC had a significant effect on hepatotoxicity (OR = 1.079, 95% CI 1.044–1.116, p = 6.9 × 10−6; OR = 0.808, 95% CI 0.711–0.917, p = 0.001, respectively). Patient's age, eGFR before MTX infusion, and co‐administration of vindesine had a significant effect on AKI (OR = 0.960, 95% CI 0.935–0.986, p = 0.003; OR = 1.009, 95% CI 1.001–1.017, p = 0.034; OR = 5.463, 95% CI 1.793–16.646, p = 0.003, respectively). LDH and Co‐administration of vindesine had a significant effect on myelosuppression (OR = 0.985, 95% CI 0.972–0.998, p = 0.025; OR = 3.070, 95% CI 1.032–9.133, p = 0.044). What is New and Conclusion Our study demonstrated that co‐administration of VDS, eGFR before MTX infusion, and the baseline index of laboratory examinations including ALT, WBC, LDH may be useful biomarkers for predicting MTX‐induced toxicities.

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“…In the second cycle of our patient’s treatment, considering our patient suffered from diabetes which is a proven risk factor for high-dose methotrexate-associated AKI in lymphoma patients. 11 Fotemustine, another alkylating agent, was also proved to be effective in glioma patients with MGMT promoter methylation compared to unmethylated MGMT. 12 Meanwhile, fotemustine, teniposide and dexamethasone (FTD) regimen has been applied in central nervous system lymphoma and been verified with no difference in 3 years PFS and OS when compared to HD-MA regimen (high-dose methotrexate plus cytarabine) in treating newly diagnosed primary central nervous system lymphoma.…”

Section: Case Presentationmentioning

confidence: 99%

Diagnosis and Individualized Treatment of Secondary Central Nervous System Lymphoma: A Case Report

Liu

et al. 2021

OTT

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Non-Hodgkin lymphoma can disseminate to the central nervous system at initiation of treatment for systemic lymphoma or spread during the relapse of systematic lymphoma with CNS involvement, which is defined as secondary central nervous system lymphoma (SCNSL). The incidence of SCNSL depends on the pathological type of lymphoma and is especially high in aggressive lymphoma. SCNSL has a poor prognosis because of the lack of effective treatment regimens. This article presents a rare case of SCNSL; an individualized treatment regimen was designed according to the genetic analyses of the patient tumor and included a Bruton's tyrosine kinase (BTK) inhibitor. After six cycles of treatment and another two cycles of rituximab, most lesions lost their metabolic activity. However, in the final stage of treatment, our patient unfortunately suffered from respiratory failure, which revealed that we should pay attention to Pneumocystis jirovecii pneumonia during ibrutinib treatment.

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Diabetes is a risk factor for high-dose methotrexate-associated AKI in lymphoma patients

Cited by 10 publications

References 33 publications

Low Serum Albumin Level Is a Risk Factor for Delayed Methotrexate Elimination in High-Dose Methotrexate Treatment

Low Serum Albumin Level Is a Risk Factor for Delayed Methotrexate Elimination in High-Dose Methotrexate Treatment

Risk factors for high‐dose methotrexate associated toxicities in patients with primary central nervous system lymphoma

Diagnosis and Individualized Treatment of Secondary Central Nervous System Lymphoma: A Case Report

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