Impact of Obesity on Chemotherapy Pharmacokinetics, Toxicity, and Survival Outcomes in Pediatric Acute Lymphoblastic Leukemia.
6 affiliations
- 1Pediatric Hematology Oncology, Cohen Children's Medical Center, New Hyde Park, USA.
- 2Pediatrics, Cohen Children's Medical Center, New Hyde Park, USA.
- 3Epidemiology and Biostatistics, The City University of New York (CUNY) Graduate School of Public Health and Health Policy, New York City, USA.
- 4General Practice, Jagadguru Sri Shivarathreeshwara (JSS) University, Mysore, IND.
- 5Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, USA.
- 6Pediatrics, Saint Peter's University Hospital, New Brunswick, USA.
Abstract
Obesity is increasingly prevalent among children and adolescents and may influence chemotherapy pharmacokinetics, treatment-related toxicity, and clinical outcomes in pediatric acute lymphoblastic leukemia (ALL). This narrative review evaluates current evidence regarding the effects of obesity on drug disposition, chemotherapy-associated toxicity, dosing considerations, and survival outcomes in pediatric ALL. Obesity alters body composition and may affect hepatic and renal physiology; however, its pharmacokinetic effects vary among therapeutic agents. Studies demonstrate associations between greater body size or adiposity and delayed high-dose methotrexate elimination, modestly reduced pegaspargase clearance, and lower thioguanine nucleotide concentrations during mercaptopurine maintenance, although these findings have not consistently translated into differences in systemic exposure or treatment efficacy. Obesity has also been associated with hepatotoxicity, pancreatitis, conjugated hyperbilirubinemia, and vincristine-induced peripheral neuropathy. Importantly, persistent overweight or obesity and extreme obesity have been associated with inferior survival outcomes or increased relapse risk in some cohorts, although the mechanisms underlying these associations remain incompletely understood. Current evidence does not support generalized chemotherapy dose reduction based solely on obesity. Instead, management should remain drug- and protocol-specific and incorporate organ function, pharmacogenetics, therapeutic drug monitoring when available, and observed toxicity. Prospective studies integrating longitudinal body composition with pharmacokinetic, pharmacodynamic, toxicity, and survival measures are needed to define whether specific patient subgroups may benefit from individualized dosing strategies.
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BibTeX
@article{nair2026impact,
title = {{Impact of Obesity on Chemotherapy Pharmacokinetics, Toxicity, and Survival Outcomes in Pediatric Acute Lymphoblastic Leukemia.}},
author = {Arun Nair and Gillian Graifman and U Tahir and Riddhi Modi and Ranya Parekh and Rajesh Varma Cp and Akash Khanal},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.116568},
url = {https://europepmc.org/article/MED/42903475},
note = {CC BY},
}
RIS
TY - JOUR
TI - Impact of Obesity on Chemotherapy Pharmacokinetics, Toxicity, and Survival Outcomes in Pediatric Acute Lymphoblastic Leukemia.
AU - Arun Nair
AU - Gillian Graifman
AU - U Tahir
AU - Riddhi Modi
AU - Ranya Parekh
AU - Rajesh Varma Cp
AU - Akash Khanal
PY - 2026
DA - 2026/09/20
JO - Cureus
DO - 10.7759/cureus.116568
UR - https://europepmc.org/article/MED/42903475
AB - Obesity is increasingly prevalent among children and adolescents and may influence chemotherapy pharmacokinetics, treatment-related toxicity, and clinical outcomes in pediatric acute lymphoblastic leukemia (ALL). This narrative review evaluates current evidence regarding the effects of obesity on drug disposition, chemotherapy-associated toxicity, dosing considerations, and survival outcomes in pediatric ALL. Obesity alters body composition and may affect hepatic and renal physiology; however, its pharmacokinetic effects vary among therapeutic agents. Studies demonstrate associations between greater body size or adiposity and delayed high-dose methotrexate elimination, modestly reduced pegaspargase clearance, and lower thioguanine nucleotide concentrations during mercaptopurine maintenance, although these findings have not consistently translated into differences in systemic exposure or treatment efficacy. Obesity has also been associated with hepatotoxicity, pancreatitis, conjugated hyperbilirubinemia, and vincristine-induced peripheral neuropathy. Importantly, persistent overweight or obesity and extreme obesity have been associated with inferior survival outcomes or increased relapse risk in some cohorts, although the mechanisms underlying these associations remain incompletely understood. Current evidence does not support generalized chemotherapy dose reduction based solely on obesity. Instead, management should remain drug- and protocol-specific and incorporate organ function, pharmacogenetics, therapeutic drug monitoring when available, and observed toxicity. Prospective studies integrating longitudinal body composition with pharmacokinetic, pharmacodynamic, toxicity, and survival measures are needed to define whether specific patient subgroups may benefit from individualized dosing strategies.
SN - 2168-8184
ER -