scholarly journals Pharmacokinetic analysis of high-dose methotrexate treatments in children with hematologic malignancies

2011 ◽  
Vol 152 (40) ◽  
pp. 1609-1617
Author(s):  
Katalin Csordás ◽  
Olivér Eipel ◽  
Márta Hegyi ◽  
Monika Csóka ◽  
Éva Pap ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Serum Levels ◽  
Hematologic Malignancies ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Serum Concentrations ◽  
Toxicity Evaluation ◽  
Dose Methotrexate

Monitoring the pharmacokinetic parameters of different anticancer drugs is necessary because they might have several side effects. Aim: Pharmacokinetic and toxicity evaluation of high-dose methotrexate treatments in children with acute lymphoblastic leukemia. Patients and methods: 43 children (28 boys, 15 girls, mean age: 7.03 years) in 147 cases were treated with 5 g/m2/24h MTX according to ALL-BFM 1995 and 2002 protocols. Methotrexate and 7-hydroxi-methotrexate levels were measured with high pressure liquid chromatography at 24, 36, 48 hours. Authors registered the development of hepatotoxicity, nephrotoxicity, grade III/IV oral mucositis. Results: Therapeutic methotrexate serum concentrations (30-100µmol/l) were achieved in 72.5% of the cases. Repeated treatments resulted similar serum levels. Hepatotoxicity and hypoproteinemia occurred in 17% and in 48.9% of the cases. There was significant correlation between serum 7-hydroxi-methotrexate and creatinine levels (p<0.05). Conclusion: 5 g/m2methotrexate resulted reliable therapeutic serum levels with mild and reversible toxicity. 7-hydroxi-methotexate measurements might be more useful than methotrexate levels to detect toxicity. Orv. Hetil., 2011, 152, 1609–1617.

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

Pharmacodynamics of High-Dose Methotrexate in Pediatric Patients

2002 ◽  
Vol 36 (9) ◽  
pp. 1344-1350 ◽  
Author(s):  
Irene Aquerreta ◽  
Azucena Aldaz ◽  
Joaquín Giráldez ◽  
Luis Sierrasesúmaga
Keyword(s):  
High Risk ◽  
Daily Practice ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
High Dose ◽  
Hematologic Toxicity ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Nonhematologic Toxicity ◽  
The Relationship

OBJECTIVE: To establish a relationship between the pharmacokinetics of high-dose methotrexate (MTX) and toxicity in children of a pediatric oncology department and to reassess MTX concentrations at which the patients would be at high risk for toxic effects. METHODS: This study included 37 patients (227 treatment courses) who received a median dose of 4.87 g/m2 of MTX in a 4-hour infusion. The population pharmacokinetic parameters of MTX were estimated by parametric (IT2B) and nonparametric methods (NPEM). Gastrointestinal, renal, and hematologic toxicity were evaluated. The relationship between pharmacokinetic parameters and toxicity was analyzed by logistic regression and multiple linear regression. RESULTS: Equations to predict hematologic and nonhematologic toxicity were obtained. An increase of 100 μmol/L in the MTX peak concentration meant a 12% (p = 0.03) higher risk of vomiting; a significant delay in MTX elimination implied a 5.76-fold higher risk of mucositis (p < 0.001). An increase of 1 μmol/L in the MTX concentration 24 hours after the end of the infusion (Cp24h) led to a 43% increase in the risk of renal toxicity (p < 0.001). Hematologic toxicity was significantly conditioned by the baseline leukocyte count and Cp24h (p < 0.001). CONCLUSIONS: The analysis of high-dose MTX pharmacokinetic/pharmacodynamic relationship to toxicity has led to equations able to predict toxicity that are easily applicable to daily practice. Cp24h >3.5 μmol/L was confirmed as an indicator of high risk of toxicity.

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

Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia

2013 ◽  
Vol 24 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Katalin Csordas ◽  
Marta Hegyi ◽  
Oliver T. Eipel ◽  
Judit Muller ◽  
Daniel J. Erdelyi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate
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