Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline

Treatment regimens for childhood acute lymphoblastic leukemia have developed steadily over the last decades, significantly improving patient outcomes. This has been achieved mainly by intensifying therapy, which also increased the risk of associated toxicity. To address this issue, therapeutic drug...

Full description

Saved in:
Bibliographic Details
Main Authors: Miguel Vieira Martins, Anna Sofie Buhl Rasmussen, Jesper Heldrup, Linea Natalie Toksvang, Marianne Ifversen, Stine Nygaard Nielsen, Kjeld Schmiegelow, Inge Margriet van der Sluis
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:EJC Paediatric Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2772610X25000121
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850118005323726848
author Miguel Vieira Martins
Anna Sofie Buhl Rasmussen
Jesper Heldrup
Linea Natalie Toksvang
Marianne Ifversen
Stine Nygaard Nielsen
Kjeld Schmiegelow
Inge Margriet van der Sluis
author_facet Miguel Vieira Martins
Anna Sofie Buhl Rasmussen
Jesper Heldrup
Linea Natalie Toksvang
Marianne Ifversen
Stine Nygaard Nielsen
Kjeld Schmiegelow
Inge Margriet van der Sluis
author_sort Miguel Vieira Martins
collection DOAJ
description Treatment regimens for childhood acute lymphoblastic leukemia have developed steadily over the last decades, significantly improving patient outcomes. This has been achieved mainly by intensifying therapy, which also increased the risk of associated toxicity. To address this issue, therapeutic drug monitoring (TDM) has been introduced in clinical research and, for certain chemotherapeutic agents, as standard of care in protocols like the ALLTogether1. The goal of TDM is to optimize delivery of a given cytotoxic drug, while minimizing the risk of toxicity. Notwithstanding, only a subset of drugs included in the backbone of ALL treatment will be eligible for TDM, since specific pharmacokinetic and pharmacodynamic properties need to apply. Despite the recent rise of innovative therapies like immunotherapy, cytotoxic drugs remain a core component of ALL treatment, making the application of TDM crucial for improving patient outcomes. Among these chemotherapeutic agents, we focus on the monitoring of asparaginase, high-dose methotrexate, 6-mercaptopurine and low dose methotrexate in maintenance therapy, tyrosine kinase inhibitors and busulfan, in order to enhance clinical effectiveness. This narrative review further explains how TDM for these drugs should be conducted and offers practical recommendations for managing them in childhood ALL treatment. Moreover, ongoing research in TDM will allow for more personalized therapy delivery in frontline strategies, while optimizing care with lesser toxicity burden for patients.
format Article
id doaj-art-cd34bf92e8a5480c8be4a08ccde2a85c
institution OA Journals
issn 2772-610X
language English
publishDate 2025-06-01
publisher Elsevier
record_format Article
series EJC Paediatric Oncology
spelling doaj-art-cd34bf92e8a5480c8be4a08ccde2a85c2025-08-20T02:35:57ZengElsevierEJC Paediatric Oncology2772-610X2025-06-01510022510.1016/j.ejcped.2025.100225Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guidelineMiguel Vieira Martins0Anna Sofie Buhl Rasmussen1Jesper Heldrup2Linea Natalie Toksvang3Marianne Ifversen4Stine Nygaard Nielsen5Kjeld Schmiegelow6Inge Margriet van der Sluis7Princess Maxima Center for Paediatric Oncology, Heidelberglaan 25, Utrecht 3584 CS, the NetherlandsDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, DenmarkChildhood Cancer and Research Unit, Skåne University Hospital, Entregatan 7, Lund 222 42, SwedenDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, DenmarkDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, DenmarkDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, DenmarkDepartment of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, Denmark; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Blegdamsvej 3B, Copenhagen 2200, DenmarkPrincess Maxima Center for Paediatric Oncology, Heidelberglaan 25, Utrecht 3584 CS, the Netherlands; Corresponding author.Treatment regimens for childhood acute lymphoblastic leukemia have developed steadily over the last decades, significantly improving patient outcomes. This has been achieved mainly by intensifying therapy, which also increased the risk of associated toxicity. To address this issue, therapeutic drug monitoring (TDM) has been introduced in clinical research and, for certain chemotherapeutic agents, as standard of care in protocols like the ALLTogether1. The goal of TDM is to optimize delivery of a given cytotoxic drug, while minimizing the risk of toxicity. Notwithstanding, only a subset of drugs included in the backbone of ALL treatment will be eligible for TDM, since specific pharmacokinetic and pharmacodynamic properties need to apply. Despite the recent rise of innovative therapies like immunotherapy, cytotoxic drugs remain a core component of ALL treatment, making the application of TDM crucial for improving patient outcomes. Among these chemotherapeutic agents, we focus on the monitoring of asparaginase, high-dose methotrexate, 6-mercaptopurine and low dose methotrexate in maintenance therapy, tyrosine kinase inhibitors and busulfan, in order to enhance clinical effectiveness. This narrative review further explains how TDM for these drugs should be conducted and offers practical recommendations for managing them in childhood ALL treatment. Moreover, ongoing research in TDM will allow for more personalized therapy delivery in frontline strategies, while optimizing care with lesser toxicity burden for patients.http://www.sciencedirect.com/science/article/pii/S2772610X25000121Therapeutic drug monitoringAcute lymphoblastic leukemiaChildren and adolescents
spellingShingle Miguel Vieira Martins
Anna Sofie Buhl Rasmussen
Jesper Heldrup
Linea Natalie Toksvang
Marianne Ifversen
Stine Nygaard Nielsen
Kjeld Schmiegelow
Inge Margriet van der Sluis
Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline
EJC Paediatric Oncology
Therapeutic drug monitoring
Acute lymphoblastic leukemia
Children and adolescents
title Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline
title_full Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline
title_fullStr Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline
title_full_unstemmed Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline
title_short Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline
title_sort therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia a practical guideline
topic Therapeutic drug monitoring
Acute lymphoblastic leukemia
Children and adolescents
url http://www.sciencedirect.com/science/article/pii/S2772610X25000121
work_keys_str_mv AT miguelvieiramartins therapeuticdrugmonitoringinthetreatmentofchildhoodacutelymphoblasticleukemiaapracticalguideline
AT annasofiebuhlrasmussen therapeuticdrugmonitoringinthetreatmentofchildhoodacutelymphoblasticleukemiaapracticalguideline
AT jesperheldrup therapeuticdrugmonitoringinthetreatmentofchildhoodacutelymphoblasticleukemiaapracticalguideline
AT lineanatalietoksvang therapeuticdrugmonitoringinthetreatmentofchildhoodacutelymphoblasticleukemiaapracticalguideline
AT marianneifversen therapeuticdrugmonitoringinthetreatmentofchildhoodacutelymphoblasticleukemiaapracticalguideline
AT stinenygaardnielsen therapeuticdrugmonitoringinthetreatmentofchildhoodacutelymphoblasticleukemiaapracticalguideline
AT kjeldschmiegelow therapeuticdrugmonitoringinthetreatmentofchildhoodacutelymphoblasticleukemiaapracticalguideline
AT ingemargrietvandersluis therapeuticdrugmonitoringinthetreatmentofchildhoodacutelymphoblasticleukemiaapracticalguideline