Akut Lenfoblastik Lösemili Çocuklarda Vinkristin İlişkili Periferik Nöropati: Prospektif Bir EMG Çalışması

Abstract

Amaç: Bu çalışmanın amacı, akut lenfoblastik lösemi (ALL) tanılı çocuklarda vinkristin tedavisine bağlı gelişen periferik nöropatinin sıklığını, elektrofizyolojik özelliklerini ve erken iyileşme paternini değerlendirmektir.
Materyal ve metod: Bu prospektif çalışmaya ALL-IC BFM 2009 protokolüne göre tedavi edilen 6–18 yaş arası 23 hasta dahil edildi. Tüm hastalara kemoterapi bitiminde ve tedavi tamamlandıktan üç ay sonra sinir iletim çalışmaları ve elektromiyografi (EMG) uygulandı. Elektrofizyolojik bulgulara göre nöropati; duyusal, motor veya mikst olarak sınıflandırıldı.
Bulgular: Tedavi sonunda hastaların %57’sinde periferik nöropati saptandı ve en sık mikst tip görüldü. Nöropati tipi ile tutulan ekstremite arasında anlamlı ilişki bulundu (p=0,037). Üç aylık takipte nöropati sıklığı %13’e geriledi. Duyusal nöropatilerin tamamı düzelirken, iki hastada motor bulguların devam ettiği görüldü. Bir hastada ise gecikmiş başlangıçlı motor nöropati gelişti.
Sonuç:  Vinkristine bağlı periferik nöropati (VIPN), ALL'li çocuklarda sıklıkla görülmekle birlikte, özellikle duyusal sinir tutulumunda belirgin erken iyileşme göstermektedir. Bununla birlikte, hastaların küçük bir kısmı kalıcı veya geç gelişen motor yetersizlikler yaşayabilir. Bu bulgular, seri elektrofizyolojik değerlendirmelerin, takip sürecinde VIPN'nin evrimi ve iyileşmesi hakkında ek bilgi sağlayabileceğini düşündürmektedir.

Keywords

• Akut lenfoblastik lösemi
• Nöropati
• Elektromiyografi
• Vinkristin

Supporting Institution

Bu çalışma herhangi bir kurum, kuruluş veya fon sağlayıcı tarafından desteklenmemiştir.

Ethical Statement

Ethical approval was obtained from the Van Yüzüncü Yıl University Faculty of Medicine Clinical Research Ethics Committee (approval no. 08, date: June 26, 2024).

Thanks

Nörofizyoloji laboratuvar ekibine ve pediatrik onkoloji hemşirelerine EMG değerlendirmelerinin koordinasyonundaki değerli katkılarından dolayı teşekkür ederiz. Ayrıca çalışmaya katılan tüm ailelere ve çocuklara da minnettarız.

Vincristine-induced Peripheral Neuropathy in Pediatric ALL: A Prospective EMG Study

Abstract

Background: The aim of this study was to evaluate the frequency, electrophysiological characteristics, and early recovery pattern of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia (ALL).
Materials and Methods: In this prospective study, 23 children aged 6 –18 years who were treated according to the ALL-IC BFM 2009 protocol were evaluated. Standardized nerve conduction studies and electromyography were performed at the end of chemotherapy and repeated three months after treatment completion. Based on electrophysiological findings, neuropathy was categorized as sensory, motor, or mixed.
Results: At the end of treatment, peripheral neuropathy was identified in 57% of the patients, most commonly as mixed-type neuropathy. Neuropathy subtype was significantly associated with the predominantly affected extremity, with motor neuropathy occurring mainly in the lower limbs (p=0.037). During follow-up, the prevalence of neuropathy decreased to 13%. All sensory neuropathies resolved completely, whereas persistent motor abnormalities remained in two patients. In addition, one patient developed motor neuropathy with delayed-onset. Conclusions: Vincristine-induced peripheral neuropathy (VIPN) is frequently observed in children with ALL but demonstrates marked early improvement, particularly in sensory nerve involvement. Nevertheless, a small proportion of patients may experience persistent or late-developing motor deficits. These findings suggest that serial electrophysiological assessments may provide additional information regarding the evolution and recovery of VIPN during follow-up.

Keywords

• Acute lymphoblastic leukemia
• Neuropathy
• Electromyography
• Vincristine

Supporting Institution

This study was not supported by any institution, organization, or funder.

Ethical Statement

Ethical approval was obtained from the Van Yüzüncü Yıl University Faculty of Medicine Clinical Research Ethics Committee (approval no. 08, date: June 26, 2024).

Thanks

We would like to thank the neurophysiology laboratory team and the pediatric oncology nurses for their valuable contributions in coordinating the EMG assessments. We are also grateful to all the families and children who participated in the study.

References

1. Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Curr Opin Neurol. 2015;28(5):500-7.
2. Stubblefield MD, Burstein HJ, Burton AW, Custodio CM, Deng GE, Ho M, et al. NCCN task force report: management of neuropathy in cancer. J Natl Compr Canc Netw. 2009;7(Suppl 5):S1-S26.
3. Triarico S, Romano A, Attinà G, Capozza MA, Maurizi P, Mastrangelo S, et al. Vincristine-induced peripheral neuropathy (VIPN) in pediatric tumors: mechanisms, risk factors, strategies of prevention and treatment. Int J Mol Sci. 2021;22(8):4112.
4. Canta A, Pozzi E, Carozzi VA. Mitochondrial dysfunction in chemotherapy-induced peripheral neuropathy (CIPN). Toxics. 2015;3(2):198-223.
5. Park SB, Cetinkaya-Fisgin A, Argyriou AA, Höke A, Cavaletti G, Alberti P. Axonal degeneration in chemotherapy-induced peripheral neurotoxicity: clinical and experimental evidence. J Neurol Neurosurg Psychiatry. 2023;94(11):962-72.
6. Sioka C, Kyritsis AP. Central and peripheral nervous system toxicity of common chemotherapeutic agents. Cancer Chemother Pharmacol. 2009;63(5):761-7.
7. Anghelescu DL, Tesney JM. Neuropathic pain in pediatric oncology: a clinical decision algorithm. Pediatr Drugs. 2019;21(2):59-70.
8. Jain P, Gulati S, Seth R, Bakhshi S, Toteja GS, Pandey RM. Vincristine-induced neuropathy in childhood acute lymphoblastic leukemia survivors: prevalence and electrophysiological characteristics. J Child Neurol. 2014;29(7):932-7.

9. Viinikainen K, Isohanni P, Kanerva J, Lönnqvist T, Lauronen L. Without ENMG, detecting pediatric vincristine neuropathy is a challenge. Clin Neurophysiol Pract. 2024;9:94-101.
10. Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD. Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996;77(7):1356-62.
11. Jeong JG, Ahn CH, Min YS, Kim SE, Kim JY, Jung TD. Electrophysiologic patterns of symptomatic vincristine-induced peripheral neuropathy in children with acute lymphocytic leukemia. J Clin Med. 2023;12(2):686.
12. Osmani K, Vignes S, Aissi M, Wade F, Milani P, Lévy BI, et al. Taxane-induced peripheral neuropathy has good long-term prognosis: a 1- to 13-year evaluation. J Neurol. 2012;259(9):1936-43.
13. Mattar M, Umutoni F, Hassan MA, Wamburu MW, Turner R, Patton JS, et al. Chemotherapy-induced peripheral neuropathy: a recent update on pathophysiology and treatment. Life (Basel). 2024;14(8):991.
14. Mora E, Smith EML, Donohoe C, Hertz DL. Vincristine-induced peripheral neuropathy in pediatric cancer patients. Am J Cancer Res. 2016;6(11):2416-30.
15. Thongmak T, Yuthasompop N. Vincristine and peripheral neuropathy in acute lymphoblastic leukemia children. J Health Sci Med Res. 2024;42(2):2023989.