Neurologic Toxicity in Children with Acute Lymphoblastic Leukemia

Yıl 2025, Cilt: 19 Sayı: 3, 105 - 112, 14.05.2025

Ahmet Serkan Özcan , Ayça Koca Yozgat , Yunus Murat Agcabelen , Melek Isik , Namık Yaşar Özbek , Hüsniye Neşe Yaralı

https://doi.org/10.12956/tchd.1584041

Öz

Objective: The objective of this study was to evaluate the occurence of neurological complications and long-term neurological sequelae in children with acute lymphoblastic leukemia (ALL). These complications were examined in relation to demographic characteristics, leukemia risk groups, and chemotherapy type.

Material and Methods: A total of 165 patients aged between 1 and 18 years of age who underwent ALL IC-BFM 2009 chemotherapy at the Pediatric Hematology Unit of Ankara Pediatric Hematology and Oncology Research and Training Hospital between June 2013 and December 2018 were retrospectively evaluated.

Results: Forty-two neurological complication episodes (1 to 3 per patient) were observed in 37 (22.4%) patients during chemotherapy. No significant differences between groups with or without neurological complications were detected in terms of age, gender, type of leukemia, risk group assignment, and relapse status (p=0.150, p= 0.170, p= 0.810, p= 0.370, and p=0.340, respectively). Complications were more likely to occur in preB-ALL patients with intermediate to high-risk status, and approximately half of the complications were identified during the early phases of treatment, i.e., induction and early consolidation; also, vincristine, methotrexate, and corticosteroids were more likely to lead to neurotoxicity. The two most common complications included polyneuropathy in 47.6% of the patients and posterior reversible encephalopathy syndrome in 16.7%. Other complications included cranial neuropathy, secondary intracranial hypertension, cortical atrophy, epilepsy, encephalopathy, myopathy, cranial thrombosis, psychotic disorder, and cerebral edema. While none of the neurological complications were associated with mortality, 21.4% of the patients had varying types of sequela, the most common being epilepsy.

Conclusion: Despite increased success rates with intense therapeutic approaches in pediatric ALL patients, 22.4% of this population experienced neurological complications. Long-term follow-up is warranted to evaluate the adverse effects and sequelae of chemotherapy more definitely.

Anahtar Kelimeler

Acute lymphoblastic leukemia, Neurologic complications, Polyneuropathy, Posterior reversible encephalopathy syndrome

Kaynakça

• Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med 2015;373:1541-52.
• Kutluk T. Çocukluk çağı kanserlerinin epidemiyolojisi. Klin Gelişim 2006: p. 11-5.
• Tekgunduz E, Demir M, Akpinar S. Prognostik faktörler ışığında akut lenfoblastik lösemi. Int J Hematol Oncol 2010;20:57–66.
• Carroll WL, Bhatla T. Acute lymphoblastic leukemia. in: Lanzkowsky P, Lipton JM, Fish JD, editors. Lanzkowsky’s Manual of Pediatric Hematology and Oncology. 6th ed. Academic Press 2016: 367–89.
• Ward E, DeSantis C, Robbins A, Kohler B, Jemal A. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 2014;64:83–103.
• Haddy TB, Mosher RB, Reaman GH. Late effects in long-term survivors after treatment for childhood acute leukemia. Clin Pediatr (Phila) 2009;48:601–8.
• Akyay A, Olcay L. Çocuklarda akut lenfoblastik lösemi tedavisinin erken ve geç yan etkileri. Turkish J Pediatr Dis 2014;1:46–54.
• Howard SC, Ribeiro RC, Pui C-H. Acute complications. in: Pui C-H, editor. Childhood Leukemias. 3rd ed. Cambridge University Press 2016: 660–700.
• ALL IC-BFM 2009. A Randomized Trial of the I-BFM-SG for the Management of Childhood non-B Acute Lymphoblastic Leukemia Final Version of Therapy Protocol from August-14-2009.
• Baytan B, Evim MS, Güler S, Güneş AM, Okan M. Acute central nervous system complications in pediatric acute lymphoblastic leukemia. Pediatr Neurol 2015;312-8.
• Nazir HF, AlFutaisi A, Zacharia M, Elshinawy M, Mevada ST, Alrawas A, et al. Vincristine-induced neuropathy in pediatric patients with acute lymphoblastic leukemia in Oman: Frequent autonomic and more severe cranial nerve involvement. Pediatr Blood Cancer 2017;64:1–5. doi: 10.1002/pbc.26677
• Hershman DL, Till C, Wright JD, Awad D, Ramsey SD, Barlow W E, et al. Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials. J Clin Oncol 2016;34:3014–22.
• Aytaç S, Yetgin S, Tavil B. Acute and long-term neurologic complications in children with acute lymphoblastic leukemia. Turk J Pediatr 2006;48:1–7.
• Diouf B, Crews KR, Lew G, Pei D, Cheng C, Bao J, et al. Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia. JAMA 2015;313:815–23.
• Wright GE, Amstutz U, Drögemöller BI, Shih J, Rassekh SR, Hayden MR, et al. Pharmacogenomics of vincristine-induced peripheral neuropathy implicates pharmacokinetic and inherited neuropathy genes. Clin Pharmacol Ther 2019;105:402–10.
• Winocur G, Wojtowicz JM, Huang J, Tannock Ian F. Physical exercise prevents suppression of hippocampal neurogenesis and reduces cognitive impairment in chemotherapy-treated rats. Psychopharmacology 2014;231:2311–20.
• Baytan B, Özdemir Ö, Demirkaya M, Evim MS, Gunes AM. Reversible posterior leukoencephalopathy induced by cancer chemotherapy. Pediatr Neurol 2010;43:197–201.
• Bilir ÖA, Dikme G, Malbora B, Evim MS, Siviş ZÖ, Tüfekçi Ö, et al. Posterior reversible encephalopathy syndrome in childhood hematological/oncological diseases: Multicenter results. J Pediatr Hematol Oncol 2020;43:462–5.
• Tang J-H, Tian J-M, Sheng M, Hu S-Y, Li Y, Zhang L-Y, et al. Study of posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia after induction chemotherapy. J Child Neurol 2016;31:279–84.
• Jeon J-S, Park S-P, Seo J-G. Posterior reversible encephalopathy syndrome due to hyponatremia. J Epilepsy Res 2014;4:31–3.
• Ranta S, Tuckuviene R, Makipernaa A, Albertsen BK, Frisk T, Tedgard U, et al. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology. Br J Haematol 2015;168:547–52.
• Ghanem KM, Dhayni RM, Al-Aridi C, Tarek N, Tamim H, Chan AKC, et al. Cerebral sinus venous thrombosis during childhood acute lymphoblastic leukemia therapy: Risk factors and management. Pediatr Blood Cancer 2017;64:1–6.
• dos Santos, AC, dos Santos, JMB, da Costa Lima, E, Land, MGP. L-asparaginase doses number as a prognostic factor in childhood acute lymphoblastic leukemia: A survival analysis study. Cancer Reports 2022; 5:e1533.
• Gillson N, Jones C, Reem RE, Rogers DL, Zumberge N, Aylward SC. Incidence and demographics of pediatric intracranial hypertension. Pediatr Neurol 2017;73:42–7.
• Peddi PF, Peddi S, Santos ES, Morgensztern D. Central nervous system toxicities of chemotherapeutic agents. Expert Rev Anticancer Ther 2014;14:857–63
• Fernández-García MÁ, Cantarin-Extremera V, Andion-Catalan M, Duat-Rodriguez A, Jimenez-Echevarria S, Bermejo-Arnedo I et al. Secondary intracranial hypertension in pediatric patients with leukemia. Pediatr Neurol 2017;77:48–53.