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Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity

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2009
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Authors
Vezmar, Sandra
Bode, Udo
Jaehde, Ulrich
Article (Published version)
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Abstract
Intrathecal and/or high-dose intravenous administration of methotrexate (MTX) in the treatment of malignancies such as acute lymphoblastic leukaemia (ALL) has been associated with cases of mild to severe neurotoxicity. The pathogenic mechanism of neurotoxicity is not clear possibly MTX-associated biochemical alterations of the folate and methyl-transfer metabolic pathways play an important role. We report a case of an adult patient treated for ALL relapse with signs of chronic leukoencephalopathy associated with MTX administration. In order to assess alterations in the folate and methyl-transfer pathway we determined 5-methyltetrahydrofolate (5-methyl-THF), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in the cerebrospinal fluid (CSF) of the patient. Three CSF samples were obtained by lumbar punction within a four-month period. Concentrations of the metabolites were measured using validated bioanalytical methods based on HPLC with UV and fluorescence detection. The result...s showed two-fold lower 5-methyl-THF levels (29.3-31.8 nmol/L) in all obtained samples compared to reference values. SAM concentrations were even more than five-fold lower in two samples (5-34.2 nmol/L). SAH concentrations were in the range 7.5-14.3 nmol/L. Our patient had pronounced alterations in the folate and methyl-transfer pathway which indicate that MTX-associated biochemical alterations of these pathways may play an important role in the development of leukoencephalopathy.

Keywords:
methotrexate / CSF / 5-methyltetrahydrofolate / S-adenosylmethionine / neurotoxicity
Source:
Journal of Medical Biochemistry, 2009, 28, 1, 11-15
Publisher:
  • Društvo medicinskih biohemičara Srbije, Beograd i Versita
Funding / projects:
  • German Academic Exchange Service (DAAD)

DOI: 10.2478/v10011-008-0027-y

ISSN: 1452-8258

WoS: 000270010700002

Scopus: 2-s2.0-60249101435
[ Google Scholar ]
2
2
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1167
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  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Vezmar, Sandra
AU  - Bode, Udo
AU  - Jaehde, Ulrich
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1167
AB  - Intrathecal and/or high-dose intravenous administration of methotrexate (MTX) in the treatment of malignancies such as acute lymphoblastic leukaemia (ALL) has been associated with cases of mild to severe neurotoxicity. The pathogenic mechanism of neurotoxicity is not clear possibly MTX-associated biochemical alterations of the folate and methyl-transfer metabolic pathways play an important role. We report a case of an adult patient treated for ALL relapse with signs of chronic leukoencephalopathy associated with MTX administration. In order to assess alterations in the folate and methyl-transfer pathway we determined 5-methyltetrahydrofolate (5-methyl-THF), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in the cerebrospinal fluid (CSF) of the patient. Three CSF samples were obtained by lumbar punction within a four-month period. Concentrations of the metabolites were measured using validated bioanalytical methods based on HPLC with UV and fluorescence detection. The results showed two-fold lower 5-methyl-THF levels (29.3-31.8 nmol/L) in all obtained samples compared to reference values. SAM concentrations were even more than five-fold lower in two samples (5-34.2 nmol/L). SAH concentrations were in the range 7.5-14.3 nmol/L. Our patient had pronounced alterations in the folate and methyl-transfer pathway which indicate that MTX-associated biochemical alterations of these pathways may play an important role in the development of leukoencephalopathy.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity
VL  - 28
IS  - 1
SP  - 11
EP  - 15
DO  - 10.2478/v10011-008-0027-y
UR  - conv_2217
ER  - 
@article{
author = "Vezmar, Sandra and Bode, Udo and Jaehde, Ulrich",
year = "2009",
abstract = "Intrathecal and/or high-dose intravenous administration of methotrexate (MTX) in the treatment of malignancies such as acute lymphoblastic leukaemia (ALL) has been associated with cases of mild to severe neurotoxicity. The pathogenic mechanism of neurotoxicity is not clear possibly MTX-associated biochemical alterations of the folate and methyl-transfer metabolic pathways play an important role. We report a case of an adult patient treated for ALL relapse with signs of chronic leukoencephalopathy associated with MTX administration. In order to assess alterations in the folate and methyl-transfer pathway we determined 5-methyltetrahydrofolate (5-methyl-THF), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in the cerebrospinal fluid (CSF) of the patient. Three CSF samples were obtained by lumbar punction within a four-month period. Concentrations of the metabolites were measured using validated bioanalytical methods based on HPLC with UV and fluorescence detection. The results showed two-fold lower 5-methyl-THF levels (29.3-31.8 nmol/L) in all obtained samples compared to reference values. SAM concentrations were even more than five-fold lower in two samples (5-34.2 nmol/L). SAH concentrations were in the range 7.5-14.3 nmol/L. Our patient had pronounced alterations in the folate and methyl-transfer pathway which indicate that MTX-associated biochemical alterations of these pathways may play an important role in the development of leukoencephalopathy.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity",
volume = "28",
number = "1",
pages = "11-15",
doi = "10.2478/v10011-008-0027-y",
url = "conv_2217"
}
Vezmar, S., Bode, U.,& Jaehde, U.. (2009). Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 28(1), 11-15.
https://doi.org/10.2478/v10011-008-0027-y
conv_2217
Vezmar S, Bode U, Jaehde U. Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity. in Journal of Medical Biochemistry. 2009;28(1):11-15.
doi:10.2478/v10011-008-0027-y
conv_2217 .
Vezmar, Sandra, Bode, Udo, Jaehde, Ulrich, "Methotrexate-associated biochemical alterations in a patient with chronic neurotoxicity" in Journal of Medical Biochemistry, 28, no. 1 (2009):11-15,
https://doi.org/10.2478/v10011-008-0027-y .,
conv_2217 .

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