Clinical and Neurophysiological Features of Vincristine-Induced Peripheral Neuropathy in Indonesian Children with Acute Lymphoblastic Leukemia
DOI:
https://doi.org/10.37287/ijghr.v7i6.584Keywords:
ALL children, vincristine, vincristine induced peripheral neuropathyAbstract
Vincristine-induced peripheral neuropathy (VIPN) is a common complication clinical pattern vary across populations, and data from Indonesian children remain limited. Objectives to describe the clinical and nerve conduction study (NCS) features of VIPN in children with ALL treated at a tertiary hospital in Indonesia. We conducted a cross-sectional study of children with ALL receiving chemotherapy recruited consecutively at Mohammad Hoesin Hospital, Palembang, from November 2023 to August 2025. Data were collected from detailed neurological and NCS examinations. Diagnosis of VIPN was made using NCS. Severity was graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Clinical features and NCS findings were evaluated. Comparisons were made between induction and maintenance phases, including the proportions of severity groups, clinical symptoms, individual nerve involvements, number of symptoms and nerves, as well as the type of lesions. A total of 118 children were enrolled; 65 (55.1%) had VIPN by NCS criteria. Neuropathy incidence was similar in induction (56.9%) and maintenance (52.8%) phases (p=0.66). Most cases were CTCAE grade 2–3. Weakness was the most frequent symptom (56.9%), while paresthesia was significantly more common in the induction phase (p=0.008). Peroneal motor nerve involvement was the most frequent NCS abnormality (91.1%), followed by median motor (50.0%) and ulnar nerves (33.7%). The induction phase was characterized by additional upper extremity nerve involvement compared to the maintenance phase, including the median (p=0.004) and ulnar (p=0.025) nerves. Sural sensory nerve abnormalities were significantly more prevalent during the maintenance phases (p=0.002). All cases demonstrated axonal, motor-predominant neuropathy, with no isolated sensory cases. VIPN is highly prevalent among Indonesian children with ALL, with motor-predominant, axonal involvement. The induction phase has more widespread nerve involvement that includes upper extremities, while the maintenance phase has more sensory sural nerve involvement, albeit more likely asymptomatic or milder. Phase-specific patterns suggest distinct pathophysiological mechanisms.
References
Abaji, R., Ceppi, F., Patel, S., Gagné, V., Xu, C. J., Spinella, J. F., Colombini, A., Parasole, R., Buldini, B., Basso, G., Conter, V., Cazzaniga, G., Leclerc, J. M., Laverdière, C., Sinnett, D., & Krajinovic, M. (2018). Genetic risk factors for VIPN in childhood acute lymphoblastic leukemia patients identified using whole-exome sequencing. Pharmacogenomics, 19(15), 1181–1193. https://doi.org/10.2217/pgs-2018-0093
Au, N. P. B., Fang, Y., Xi, N., Lai, K. W. C., & Ma, C. H. E. (2014). Probing for chemotherapy-induced peripheral neuropathy in live dorsal root ganglion neurons with atomic force microscopy. Nanomedicine: Nanotechnology, Biology, and Medicine, 10(6), 1323–1333. https://doi.org/10.1016/j.nano.2014.03.002
Cancer Therapy Evaluation Program. (2017). Common terminology criteria for adverse event (CTCAE) version 5.0. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm
Courtemanche, H., Magot, A., Ollivier, Y., Rialland, F., Leclair-Visonneau, L., Fayet, G., Camdessanché, J. P., & Péréon, Y. (2015). Vincristine-induced neuropathy: Atypical electrophysiological patterns in children. Muscle and Nerve, 52(6), 981–985. https://doi.org/10.1002/mus.24647
Diouf, B., Crews, K. R., Lew, G., Pei, D., Cheng, C., Bao, J., Zheng, J. J., Yang, W., Fan, Y., Wheeler, H. E., Wing, C., Delaney, S. M., Komatsu, M., Paugh, S. W., Robert McCorkle, J., Lu, X., Winick, N. J., Carroll, W. L., Loh, M. L., Hunger, S. P., Devidas, M, Pui, C. H., Dolan, M. E., Relling, M. V., & Evans, W. E. (2015). Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia. JAMA, 313(8), 815–823. https://doi.org/10.1001/jama.2015.0894.Association
Garniasih, D., Susanah, S., Sribudiani, Y., & Hilmanto, D. (2022). The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis. PLoS ONE, 17(6 June), 1–13. https://doi.org/10.1371/journal.pone.0269706
Gunawan, P., Hardiyani, K., & Ugrasena, I. (2023). Total Neuropathy Scale Pediatric Vincristine to detect vincristine induced peripheral neuropathy in children with Acute Lymphoblastic Leukemia. Rawal Medical Journal, 48(1), 1. https://doi.org/10.5455/rmj20220613092311
Gutierrez-Camino, A., Martin-Guerrero, I., Lopez-Lopez, E., Echebarria-Barona, A., Zabalza, I., Ruiz, I., Guerra-Merino, I., & Garcia-Orad, A. (2016). Lack of association of the CEP72 RS924607 TT genotype with vincristine-related peripheral neuropathy during the early phase of pediatric acute lymphoblastic leukemia treatment in a Spanish population. Pharmacogenetics and Genomics, 26(2), 100–102. https://doi.org/10.1097/FPC.0000000000000191
Han, Y., & Smith, M. T. (2013). Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). Frontiers in Pharmacology, 4 (December), 1–16. https://doi.org/10.3389/fphar.2013.00156
Jeong, J. G., Ahn, C. H., Min, Y. S., Kim, S. E., Kim, J. Y., & Jung, T. Du. (2023). Electrophysiologic Patterns of Symptomatic Vincristine-Induced Peripheral Neuropathy in Children with Acute Lymphocytic Leukemia. Journal of Clinical Medicine, 12(2), 1-10. https://doi.org/10.3390/jcm12020686
Kang, P. B. (2007). Pediatric nerve conduction studies and EMG. In Blum, A. S. & Rutkove , S. B. (Eds.), The clinical neurophysiology primer (First edition, pp. 369–392). Humana Press Inc.
Kaplan, J. A. (2019). Leukemia in children. Pediatrics in Review, 40(7), 319–331. https://doi.org/10.1542/pir.2018-0192
Li, T., Kandula, T., Cohn, R. J., Kiernan, M. C., Park, S. B., & Farrar, M. A. (2023). Prospective assessment of vincristine-induced peripheral neuropathy in paediatric acute lymphoblastic leukemia. Clinical Neurophysiology, 154, 157–168. https://doi.org/10.1016/j.clinph.2023.08.002
Lopez-Lopez, E., Gutierrez-Camino, A., Astigarraga, I., Navajas, A., Echebarria-Barona, A., Garcia-Miguel, P., Garcia De Andoin, N., Lobo, C., Guerra-Merino, I., Martin-Guerrero, I., & Garcia-Orad, A. (2016). Vincristine pharmacokinetics pathway and neurotoxicity during early phases of treatment in pediatric acute lymphoblastic leukemia. Pharmacogenomics, 17(7), 731–741. https://doi.org/10.2217/pgs-2016-0001
Madsen, M. L., Due, H., Ejskjær, N., Jensen, P., Madsen, J., & Dybkær, K. (2019). Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review. Cancer Chemotherapy and Pharmacology, 84(3), 471–485. https://doi.org/10.1007/s00280-019-03884-5
Ryan, C. S., Conlee, E. M., Sharma, R., Sorenson, E. J., Boon, A. J., & Laughlin, R. S. (2019). Nerve conduction normal values for electrodiagnosis in pediatric patients. Muscle and Nerve, 60(2), 155–160. https://doi.org/10.1002/mus.26499
Skiles, J. L., Chiang, C. W., Li, C. H., Martin, S., Smith, E. L., Olbara, G., Jones, D. R., Vik, T. A., Mostert, S., Abbink, F., Kaspers, G. J., Li, L., Njuguna, F., Sajdyk, T. J., & Renbarger, J. L. (2018). CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer. Pediatric Blood and Cancer, 65(3), 1–7. https://doi.org/10.1002/pbc.26854
Smith, E. M. L., Kuisell, C., Kanzawa-Lee, G. A., Bridges, C. M., Alberti, P., Cavaletti, G., Saad, R., & Park, S. (2020). Approaches to measure paediatric chemotherapy-induced peripheral neurotoxicity: a systematic review. The Lancet Haematology, 7(5), e408–e417. https://doi.org/10.1016/S2352-3026(20)30064-8
Smolik, S., Arland, L., Hensley, M. A., Schissel, D., Shepperd, B., Thomas, K., & Rodgers, C. (2018). Assessment Tools for Peripheral Neuropathy in Pediatric Oncology: A Systematic Review From the Children’s Oncology Group. Journal of Pediatric Oncology Nursing, 35(4), 267–275. https://doi.org/10.1177/1043454218762705
Starobova, H., & Vetter, I. (2017). Pathophysiology of chemotherapy-induced peripheral neuropathy. Frontiers in Molecular Neuroscience, 10(May), 1–21. https://doi.org/10.3389/fnmol.2017.00174
Tay, N., Laakso, E. L., Schweitzer, D., Endersby, R., Vetter, I., & Starobova, H. (2022). Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients. Frontiers in Molecular Biosciences, 9(1), 1-27. https://doi.org/10.3389/fmolb.2022.1015746
Triarico, S., Romano, A., Attinà, G., Capozza, M. A., Maurizi, P., Mastrangelo, S., & Ruggiero, A. (2021). Vincristine-induced peripheral neuropathy (Vipn) in pediatric tumors: Mechanisms, risk factors, strategies of prevention and treatment. International Journal of Molecular Sciences, 22(8), 1-13. https://doi.org/10.3390/ijms22084112
Tunjungsari, D. A., Gunawan, P. I., & Ugrasena, I. D. G. (2021). Risk factors of vincristine-induced peripheral neuropathy in acute lymphoblastic leukaemia children. Journal of Medical Investigation, 68(3.4), 232–237. https://doi.org/10.2152/jmi.68.232
Uittenboogaard, A., Neutel, C. L. G., Ket, J. C. F., Njuguna, F., Huitema, A. D. R., Kaspers, G. J. L., & van de Velde, M. E. (2022). Pharmacogenomics of Vincristine-Induced Peripheral Neuropathy in Children with Cancer: A Systematic Review and Meta-Analysis. Cancers, 14(3), 1-24. https://doi.org/10.3390/cancers14030612
UKK Hematologi Onkologi IDAI. (2018). Buku panduan protokol leukemia limfoblastik akut 2018. Balai Penerbit Ikatan Dokter Anak Indonesia.
UKK Hematologi Onkologi IDAI. (2024). Protokol Nasional Leukemia Limfoblastik Akut pada Anak 2024. UKK Hematologi Onkologi IDAI.
Viinikainen, K., Isohanni, P., Kanerva, J., Lönnqvist, T., & Lauronen, L. (2024). Without ENMG, detecting pediatric vincristine neuropathy is a challenge. Clinical Neurophysiology Practice, 9, 94–101. https://doi.org/10.1016/j.cnp.2024.01.005
Wang, L., Yao, X., & Yang, L. (2025). Global, regional, and national burden of children and adolescents with acute lymphoblastic leukemia from 1990 to 2021: a systematic analysis for the global burden of disease study 2021. Frontiers in Public Health, 13(January), 1-9. https://doi.org/10.3389/fpubh.2025.1525751
Zajaczkowską, R., Kocot-Kępska, M., Leppert, W., Wrzosek, A., Mika, J., & Wordliczek, J. (2019). Mechanisms of chemotherapy-induced peripheral neuropathy. International Journal of Molecular Sciences, 20(6), 1-29. https://doi.org/10.3390/ijms20061451.
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