Etiological Profile and Clinical Outcomes Of Acute Neurotoxicity During Pediatric ALL Treatment in a Developing Country
DOI:
https://doi.org/10.51253/pafmj.v76iSUPPL-5.12747Keywords:
Acute lymphoblastic leukemia, Leukoencephalopathy, Meningoencephalitis, NeurotoxicityAbstract
Objective: To determine the causes, clinical manifestations, and consequences of acute neurotoxicity in pediatric patients undergoing therapy for acute lymphoblastic leukemia (ALL).
Study Design: A prospective longitudinal study.
Place and Duration of Study: Pediatric Oncology Department, Indus Hospital and Health Network, Karachi, Pakistan, from May to Oct 2021.
Methodology: Patients presenting within 48 hours of developing neurological changes were labeled to have acute neurotoxicity. Cerebrospinal fluid (CSF) analysis, neuroimaging, metabolic profile, and an electroencephalogram (EEG) were performed as needed. Neurotoxicity types, causes, and outcomes were analyzed.
Results: Among the 511 children studied, 36 (7.0%) developed neurotoxicity, while the remaining 475 showed no signs of neurotoxicity at six months of follow-up and were censored from the analysis. Methotrexate leukoencephalopathy (MLE) was the most common type of neurotoxicity, affecting 16 children during intensive and maintenance treatment. Meningoencephalitis and posterior reversible encephalopathy syndrome (PRES) were identified in seven and four children, respectively. Of the 36 children with neurotoxicity, 29 (80.5%) achieved full recovery. However, seven children (19.5%) died; one due to disease recurrence and six from various complications.
Conclusion: Most patients with neurotoxicity had complete recovery. The major causes of morbidity and mortality were MTX toxicity and CNS infections. More severe methotrexate neurotoxicity in our cohort is an important finding and needs further studies to understand the underlying cause.
Downloads
References
1. PDQ Pediatric Treatment Editorial Board. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Health Professional Version. 2025 Apr 21. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–.
2. Jabbar N, Mansoor N, Nadeem K, Maqsood S, Butt Z, Ashraf S. Prednisolone Prophase for a Week Versus Upfront Multiagent Chemotherapy in Childhood Acute Lymphoblastic Leukemia: An Analysis With Reference to Induction Mortality in a Developing Country. J Pediatr Hematol Oncol 2020; 42(3): 181-184. https://doi.org/10.1097/MPH.0000000000001636
3. Ahmad I, Ghafoor T, Ullah A, Naz S, Tahir M, Ahmed S, et al. Pediatric Acute Lymphoblastic Leukemia: Clinical Characteristics, Treatment Outcomes, and Prognostic Factors: 10 Years' Experience From a Low- and Middle-Income Country. JCO Glob Oncol 2023; 9: e2200288.
https://doi.org/10.1200/GO.22.00288
4. Millan NC, Pastrana A, Guitter MR, Zubizarreta PA, Monges MS, Felice MS. Acute and sub-acute neurological toxicity in children treated for acute lymphoblastic leukemia. Leuk Res 2018; 65: 86-93.
https://doi.org/10.1016/j.leukres.2017.12.010
5. Parasole R, Petruzziello F, Menna G, Mangione A, Cianciulli E, Buffardi S, et al. Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution. Leuk Lymphoma 2010; 51(6): 1063-1071.
https://doi.org/10.3109/10428191003754608
6. Anastasopoulou S, Nielsen RL, Als-Nielsen B, Banerjee J, Eriksson MA, Helenius M, et al. Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes. Haematologica 2022; 107(10): 2318-2328.
https://doi.org/10.3324/haematol.2021.280016
7. Aytaç S, Yetgin S, Tavil B. Acute and long-term neurologic complications in children with acute lymphoblastic leukemia. Turk J Pediatr 2006; 48(1): 1-7.
8. Masqati N, Fadoo Z, Sajid MI, Bhatti OA, Bhatti A. Neurological complications in children with acute lymphoblastic leukemia. Med J South Punjab 2023; 5(1): 33-40.
https://doi.org/10.61581/MJSP.VOL05/01/6
9. Rahiman EA, Rajendran A, Sankhyan N, Singh P, Muralidharan J, Bansal D, et al. Acute neurological complications during acute lymphoblastic leukemia therapy: A single-center experience over 10 years. Indian J Cancer 2021; 58(4): 545-552.
https://doi.org/10.4103/ijc.IJC_422_19
10. Hamoda A, Bedair M, Semary SF, Youssef A, Hafez H. Patterns and Outcomes of Acute Central Nervous System Complications During Treatment of Childhood Acute Lymphoblastic Leukemia: A Single-center Experience. J Pediatr Hematol Oncol 2024; 46(2): 72-79.
https://doi.org/10.1097/MPH.0000000000002797
11. Sági JC, Gézsi A, Egyed B, Jakab Z, Benedek N, Attarbaschi A, et al. Pharmacogenetics of the Central Nervous System-Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia. Cancers 2021; 13(10): 2333.
https://doi.org/10.3390/cancers13102333
12. Filbin M, Monje M. Developmental origins and emerging therapeutic opportunities for childhood cancer. Nat Med 2019; 25(3): 367-376. https://doi.org/10.1038/s41591-019-0383-9
13. Amatruda JF. Modeling the developmental origins of pediatric cancer to improve patient outcomes. Dis Model Mech 2021; 14(2): dmm048930. https://doi.org/10.1242/dmm.048930
14. Ramalingam R, Kaur H, Scott JX, Sneha LM, Arunkumar G, Srinivasan A, et al. Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients. Cancer Chemother Pharmacol 2022; 89(3): 393-400.
https://doi.org/10.1007/s00280-022-04405-7
15. Akshay L, Prabodha D, Sonali M, Suprava N, Ashutosh P, Biswajit B. Methotrexate (MTX) Induced Leukoencephalo-pathy(LE) and Relation of Vitamin B12, Folate and/or Homocysteine Levels with MTX Toxicity: A Prospective Study. Blood 2021; 138(Suppl 1): 4374.
https://doi.org/10.1182/blood-2021-153241
16. Xiao X, Chu SJ, Tang JH, Zhang LY, Zhang BB. Leukoencephalopathy in children with acute lymphoblastic leukemia after chemotherapy: a retrospective monocenter study. Transl Cancer Res 2023; 12(2): 340-350.
https://doi.org/10.21037/tcr-22-2180
17. Lin W, Xie J, Zhang J, Cheng H, Cui H, Zhang Y, et al. Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia during remission induction chemotherapy: a single-center retrospective study. Minerva Pediatr 2023; 75(6): 808-816.
https://doi.org/10.23736/S2724-5276.19.05675-5
18. Sabin ND, Cheung YT, Reddick WE, Bhojwani D, Liu W, Glass JO, et al. The Impact of Persistent Leukoencephalopathy on Brain White Matter Microstructure in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Chemotherapy Only. AJNR Am J Neuroradiol 2018; 39(10): 1919-1925.
https://doi.org/10.3174/ajnr.A5791
19. Gandy K, Scoggins MA, Jacola LM, Litten M, Reddick WE, Krull KR. Structural and Functional Brain Imaging in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia Treated with Chemotherapy: A Systematic Review. JNCI Cancer Spectr 2021; 5(5): pkab069. https://doi.org/10.1093/jncics/pkab069
20. Salvador C, Salvador R, Willeit P, Kuntner C, Haid A, Müller T, et al. Hyponatremia During Induction Therapy in Distinct Pediatric Oncological Cohorts: A Retrospective Study. Front Oncol 2021; 11: 708875.
Downloads
Published
License
Copyright (c) 2026 Sundus Hashmani, Anushe Mohsin Feroze, Zohra Rafique, Syed Ahmer Hamid, Muhammad Rafie Raza, Muhammad Shamvil Ashraf

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.





