Pharmacokinetics of 6-Thioguanine and 6-Mercaptopurine Combination Maintenance Therapy of Childhood ALL: Hypothesis and Case Report

Stine N Nielsen; Thomas L Frandsen; Jacob Nersting; Lisa L Hjalgrim; Kjeld Schmiegelow

doi:10.1097/MPH.0000000000000246

Pharmacokinetics of 6-Thioguanine and 6-Mercaptopurine Combination Maintenance Therapy of Childhood ALL: Hypothesis and Case Report

Stine N Nielsen, Thomas L Frandsen, Jacob Nersting, Lisa L Hjalgrim, Kjeld Schmiegelow

Institut for Klinisk Medicin

4 Citationer (Scopus)

Abstract

Methotrexate/6-mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia is challenged by treatment-related hepatotoxicity, failure to achieve the myelosuppressive target, and lack of direct parameters for monitoring treatment efficacy or even intensity. Patients with low thiopurine methyltransferase (TPMT) activity have lower levels of hepatotoxic methylated thiopurine metabolites (MeMPs), higher levels of thioguanine nucleotides (TGNs), and reduced relapse rates. Addition of 6-thioguanine to maintenance therapy of a child with ALL and high TPMT activity increased the TGN/MeMP index in erythrocytes 5.5-fold, mimicking the more favorable thiopurine metabolism seen in patients with low TPMT activity.

Originalsprog	Engelsk
Tidsskrift	Journal of Pediatric Hematology/Oncology
Vol/bind	37
Udgave nummer	3
Sider (fra-til)	e206-e209
Antal sider	4
ISSN	1077-4114
DOI	https://doi.org/10.1097/MPH.0000000000000246
Status	Udgivet - 7 apr. 2015

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10.1097/MPH.0000000000000246

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@article{e9f8d35ee3474ecf9959d2d1974dc28b,

title = "Pharmacokinetics of 6-Thioguanine and 6-Mercaptopurine Combination Maintenance Therapy of Childhood ALL: Hypothesis and Case Report",

abstract = "Methotrexate/6-mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia is challenged by treatment-related hepatotoxicity, failure to achieve the myelosuppressive target, and lack of direct parameters for monitoring treatment efficacy or even intensity. Patients with low thiopurine methyltransferase (TPMT) activity have lower levels of hepatotoxic methylated thiopurine metabolites (MeMPs), higher levels of thioguanine nucleotides (TGNs), and reduced relapse rates. Addition of 6-thioguanine to maintenance therapy of a child with ALL and high TPMT activity increased the TGN/MeMP index in erythrocytes 5.5-fold, mimicking the more favorable thiopurine metabolism seen in patients with low TPMT activity.",

keywords = "6-Mercaptopurine, Antimetabolites, Antineoplastic, Child, Erythrocytes, Female, Humans, Methyltransferases, Neoplasm Recurrence, Local, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Remission Induction, Thioguanine",

author = "Nielsen, {Stine N} and Frandsen, {Thomas L} and Jacob Nersting and Hjalgrim, {Lisa L} and Kjeld Schmiegelow",

year = "2015",

month = apr,

day = "7",

doi = "10.1097/MPH.0000000000000246",

language = "English",

volume = "37",

pages = "e206--e209",

journal = "Journal of Pediatric Hematology/Oncology",

issn = "1077-4114",

publisher = "Lippincott Williams & Wilkins",

number = "3",

}

TY - JOUR

T1 - Pharmacokinetics of 6-Thioguanine and 6-Mercaptopurine Combination Maintenance Therapy of Childhood ALL

T2 - Hypothesis and Case Report

AU - Nielsen, Stine N

AU - Frandsen, Thomas L

AU - Nersting, Jacob

AU - Hjalgrim, Lisa L

AU - Schmiegelow, Kjeld

PY - 2015/4/7

Y1 - 2015/4/7

N2 - Methotrexate/6-mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia is challenged by treatment-related hepatotoxicity, failure to achieve the myelosuppressive target, and lack of direct parameters for monitoring treatment efficacy or even intensity. Patients with low thiopurine methyltransferase (TPMT) activity have lower levels of hepatotoxic methylated thiopurine metabolites (MeMPs), higher levels of thioguanine nucleotides (TGNs), and reduced relapse rates. Addition of 6-thioguanine to maintenance therapy of a child with ALL and high TPMT activity increased the TGN/MeMP index in erythrocytes 5.5-fold, mimicking the more favorable thiopurine metabolism seen in patients with low TPMT activity.

AB - Methotrexate/6-mercaptopurine maintenance therapy of childhood acute lymphoblastic leukemia is challenged by treatment-related hepatotoxicity, failure to achieve the myelosuppressive target, and lack of direct parameters for monitoring treatment efficacy or even intensity. Patients with low thiopurine methyltransferase (TPMT) activity have lower levels of hepatotoxic methylated thiopurine metabolites (MeMPs), higher levels of thioguanine nucleotides (TGNs), and reduced relapse rates. Addition of 6-thioguanine to maintenance therapy of a child with ALL and high TPMT activity increased the TGN/MeMP index in erythrocytes 5.5-fold, mimicking the more favorable thiopurine metabolism seen in patients with low TPMT activity.

KW - 6-Mercaptopurine

KW - Antimetabolites, Antineoplastic

KW - Child

KW - Erythrocytes

KW - Female

KW - Humans

KW - Methyltransferases

KW - Neoplasm Recurrence, Local

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Prognosis

KW - Remission Induction

KW - Thioguanine

U2 - 10.1097/MPH.0000000000000246

DO - 10.1097/MPH.0000000000000246

M3 - Journal article

C2 - 25171455

SN - 1077-4114

VL - 37

SP - e206-e209

JO - Journal of Pediatric Hematology/Oncology

JF - Journal of Pediatric Hematology/Oncology

IS - 3

ER -

Pharmacokinetics of 6-Thioguanine and 6-Mercaptopurine Combination Maintenance Therapy of Childhood ALL: Hypothesis and Case Report

Abstract

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