scholarly journals Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Shi-Long Yang ◽  
Fen-Ying Zhao ◽  
Hua Song ◽  
Di-Ying Shen ◽  
Xiao-Jun Xu
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Serum Creatinine ◽  
Lymphoblastic Leukemia ◽  
Serum Creatinine Concentration ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Creatinine Ratio ◽  
Creatinine Concentration ◽  
Dose Methotrexate

Although Methotrexate (MTX) is an effective drug for the treatment of acute lymphoblastic leukemia (ALL), the toxicity remains a significant problem. In this prospective study, fifty-four patients with ALL were enrolled. 3 g or 5 g MTX/m2was administered over 24 hours. Serum MTX concentrations were determined in 24, 48, and 96 hours after MTX infusion. Serum creatinine concentrations and creatinine clearance rate (CCR) were determined before and 24 and 48 hours after MTX infusion. A total of 173 courses of MTX infusion were administered. The serum creatinine concentrations did not change much after MTX infusion while the CCR was gradually decreased. MTX clearance status was independently related to CCR decrease, with the risk of 8.07 to develop renal impairment in patients with delayed MTX elimination. Serum creatinine concentration, serum creatinine ratio, CCR, and CCR ratio at 24 hours were all related to MTX elimination delay. Patients with serum creatinine level >35.0 μmol/L, creatinine ratio >1.129, or CCR <100.0 mL/min were more likely to undergo MTX elimination delay. In conclusion, MTX could induce transient renal impairment and compromised renal function will delay MTX clearance. The serum creatinine concentration and the ratio and CCR are useful tools for evaluating MTX elimination status.

scholarly journals Population Pharmacokinetics of High-Dose Methotrexate in Chinese Pediatric Patients With Acute Lymphoblastic Leukemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuan Gao ◽  
Xiao-Wen Qian ◽  
Xiao-Hua Zhu ◽  
Yi Yu ◽  
Hui Miao ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Lymphoblastic Leukemia ◽  
Serum Creatinine ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Concentration Data ◽  
Dose Methotrexate ◽  
Population Pk

High-dose methotrexate (HD-MTX) is widely used in pediatric acute lymphoblastic leukemia (ALL) treatment regimens. In this study, we aimed to develop a population pharmacokinetic (PK) model of HD-MTX in Chinese pediatric patients with ALL for designing personalized dosage regimens. In total, 4,517 MTX serum concentration data for 311 pediatric patients with ALL, aged 0.75–15.2 years and under HD-MTX treatment, were retrospectively collected at a tertiary Children’s Hospital in China. The non-linear mixed-effect model was used to establish the population PK model, using NONMEM software. The potential covariate effects of age, body weight, and biochemical measurements (renal and liver function) on MTX PK disposition were investigated. The model was then evaluated using goodness-of-fit, visual predictive check. MTX PK disposition was described using a three-compartment model reasonable well. Body weight, implemented as a fixed allometric function on all clearance and volume of distribution parameters, showed a substantial improvement in model fit. The final population model demonstrated that the MTX clearance estimate in a typical child with body weight of 19 kg was 6.9 L/h and the central distribution of volume estimate was 20.7 L. The serum creatinine significantly affected the MTX clearance, with a 0.97% decrease in clearance per 1 μmol/L of serum creatinine. Other covariates (e.g., age, sex, bilirubin, albumin, aspartate transaminase, concomitant medication) did not significantly affect PK properties of MTX. The proposed population PK model could describe the MTX concentration data in Chinese pediatric patients with ALL. This population PK model combined with a maximum a posteriori Bayesian approach could be used to estimate individual PK parameters, and optimize personalized MTX therapy in target patients, thus aiming to reduce toxicity and improve treatment outcomes.

scholarly journals Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort

2021 ◽  
Author(s):  
Riitta Niinimäki ◽  
Henri Aarnivala ◽  
Joanna Banerjee ◽  
Tytti Pokka ◽  
Kaisa Vepsäläinen ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Optimal Dosage ◽  
High Dose Methotrexate ◽  
Reduced Dose ◽  
Dose Methotrexate ◽  
Antileukemic Effect ◽  
Folinic Acid Rescue ◽  
High Doses

Abstract Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

scholarly journals High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia

2018 ◽  
Vol 10 ◽  
pp. 44-51 ◽  
Author(s):  
Wasil Jastaniah ◽  
Naglla Elimam ◽  
Khalid Abdalla ◽  
Aeshah A. AlAzmi ◽  
Mohammed Aseeri ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Infections during high dose methotrexate therapy in childhood acute lymphoblastic leukemia (ALL)

2016 ◽  
Vol 45 (1) ◽  
pp. 6-13
Author(s):  
Taskina Mosleh ◽  
Gulsan Ara Zahan ◽  
Md Kamrul Ahsan Khan ◽  
Afiqul Islam
Keyword(s):  
Prospective Observational Study ◽  
Lymphoblastic Leukemia ◽  
Case Fatality ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Childhood All ◽  
Dose Methotrexate ◽  
Incidence Risk ◽  
To Receive ◽  
Hdmtx Therapy

High-dose methotrexate (HDMTX) therapy is an effective therapy for childhood ALL, which is frequently associated with side effects like infection in our centre. It prolongs hospital stay, delays chemotherapy and causes more economic burden on patients.This study was done to identify the incidence, risk factors and severity of infection among children with ALL during HDMTX therapy.This prospective observational study was conducted among 50 patients suffering from acute lymphoblastic leukemiascheduled to receive HDMTX at the Department of Pediatric Hemato-oncology of BSMMU. It was carried out from January 2012 to June 2012.The end result showed, 19 (38%) patients su_ered from infection; among them microbiologically documented infections found in 9 occasions, where gram negative bacilli - E.coli 4(44.4%) & Pseudomonas 3(33.33%) were predominant organisms. Gastrointestinal tract (GIT) was the most common site (8,42.11%).The rate of infection is significantly higher in children <5 yrs(78.94%). Mortality rate was 6%. As the infection and case fatality rate is quite high with HDMTX therapy, we recommend to use this drug with caution.Bangladesh Med J. 2016 Jan; 45 (1): 6-13

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