Research Article
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Evaluation of clinical neurological complications and prognosis in children with acute lymphoblastic leukemia

Year 2023, Volume: 28 Issue: 2, 149 - 158, 23.05.2023
https://doi.org/10.21673/anadoluklin.1201526

Abstract

Aim: The aim of the present study is to evaluate the neurological complications, which occur during the treatment process, to determine the risk factors of these complications and their impact on children with acute lymphoblastic leukemia.

Methods: In our study, patients who were younger than 18 years of age with the diagnosis of acute lymphoblastic leukemia and who were treated with Berlin Frankfurt Munster (BFM) TR ALL-2000 chemotherapy protocol between January 2006 and December 2011 were retrospectively retrieved from our medical records. A total number of 200 patients were included in the study and 6 of them were excluded due to central nervous system involvement when diagnosed. Demographic, clinical, radiological, neurological findings and laboratory results of 194 patients were analyzed together. Patients were divided into two groups regarding the occurrence of neurological complications and were compared in terms of gender, age, laboratory findings, treatment, survival and relapse.

Results: Neurological complications were observed in 28 of 194 patients throughout the treatment process who did not have a central nervous system involvement at the time of diagnosis. The most common neurological complication was convulsion (7.7%). Although the majority of patients with neurological complications were male, no statistically significant correlation was found between gender, age and the complication occurrence. It was detected that the leukocyte levels at the time of diagnosis were high in patients with neurological complications. These high levels were found to be related with the increased the risk of complication occurrence during chemotherapy. Although the survival rate of patients with neurological complications were lower, no statistically significant difference was found in terms of survival rate between these two groups.

Conclusion: It should be kept in mind that high leukocyte level at the time of diagnosis, which is known to be a poor prognostic factor in pediatric patients with acute lymphoblastic leukemia, might also be a precursor of neurological complications those occur during the treatment.

References

  • Karbuz A, Yaralı N, Işık P, Bay A, Kara A, Tunç B. Akut lösemi hastalarının demografik özellikleri ve tedavi sırasında görülen komplikasyonları: tek merkez deneyimi. Türkiye Çocuk Hast Derg. 2017;1:19-26
  • Aricò M, Valsecchi MG, Rizzari C, et al. Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy. J Clin Oncol. 2008;26(2):283-9.
  • Chen CY, Zimmerman RA, Faro S, Bilaniuk LT, Chou TY, Molloy PT. Childhood leukemia: central nervous system abnormalities during and after treatment. AJNR Am J Neuroradiol. 1996;17(2):295-310.
  • Gervasini G, Vagace JM. Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia. Front Genet. 2012;3:249.
  • Vagace JM, de la Maya MD, Caceres-Marzal C, Gonzalez de Murillo S, Gervasini G. Central nervous system chemotoxicity during treatment of pediatric acute lymphoblastic leukemia/lymphoma. Crit Rev Oncol Hematol. 2012;84(2):274-86.
  • Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371(9617):1030-43.
  • Bhatia S. Disparities in cancer outcomes: lessons learned from children with cancer. Pediatr Blood Cancer. 2011;56(6):994-1002.
  • Banerjee J, Niinimäki R, Lähteenmäki P, et al. The spectrum of acute central nervous system symptoms during the treatment of childhood acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2020;67(2):e27999.
  • 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.
  • Baytan B, Evim MS, Güler S, Güneş AM, Okan M. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia. Pediatr Neurol. 2015;53(4):312-8.
  • Parasole R, Petruzziello F, Menna G, et al. Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution. Leuk Lymphoma. 2010;51(6):1063-71.
  • Aytac 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.
  • Vora A, Goulden N, Wade R, et al. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013;14(3):199-209.
  • Schmidt K, Schulz AS, Debatin KM, Friedrich W, Classen CF. CNS complications in children receiving chemotherapy or hematopoietic stem cell transplantation: retrospective analysis and clinical study of survivors. Pediatr Blood Cancer. 2008;50(2):331-6.
  • Mahoney DH Jr, Shuster JJ, Nitschke R, et al. Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy - a Pediatric Oncology Group study. J Clin Oncol. 1998;16(5):1712-22.
  • Anastasopoulou S, Heyman M, Eriksson MA, et al. Seizures during treatment of childhood acute lymphoblastic leukemia: A population-based cohort study. Eur J Paediatr Neurol. 2020;27:72-7.
  • Taylor OA, Brown AL , Brackett J, et al. Disparities in neurotoxicity risk and outcomes among pediatric acute lymphoblastic leukemia patients. Clin Cancer Res. 2018;24(20):5012-7.
  • Rahman AT, Mannan MA, Sadeque S. Acute and long-term neurological complications in children with acute lymphoblastic leukemia. Bangladesh Med Res Counc Bull. 2008;34(3):90-3.
  • Reddick WE, Glass JO, Helton KJ, et al. Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol. 2005;26(5):1263-9.
  • Kuskonmaz B, Unal S, Gumruk F, Cetin M, Tuncer AM, Gurgey A. The neurologic complications in pediatric acute lymphoblastic leukemia patients excluding leukemic infiltration. Leuk Res. 2006;30(5):537-41.
  • Apak H, Ekici B, Albayram S, et al. The impact of low dose methotrexate on cerebral complications in acute lymphoblastic leukemia treatment. Turk Arch Pediatr. 2009;44(2):62-7.
  • Dufourg MN, Landman-Parker J, Auclerc MF, et al. Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children. Leukemia. 2007;21(2):238-47.
  • Rubnitz JE, Relling MV, Harrison PL, et al. Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia. Leukemia 1998;12(8):1176-81.
  • Fisher MJ, Khademian ZP, Simon EM, Zimmerman RA, Bilaniuk LT. Diffusion-weighted MR imaging of early methotrexate-related neurotoxicity in children. AJNR Am J Neuroradiol. 2005;26(7):1686-9.
  • Lee AC, Li CH, Wong YC. Transient encephalopathy following high-dose methotrexate. Med Pediatr Oncol. 2003;41(1):101.
  • Kim H, Lee JH, Choi SJ, et al. Risk score model for fatal intracranial hemorrhage. Leukemia. 2006;20(5):770-6.
  • Pui CH, Campana D, Pei D, et al. Treatment of childhood acute lymphoblastic leukemia without prophylactic cranial irradiation. N Engl J Med. 2009;360(26):2730-41.
  • Lo Nigro L, Di Cataldo A, Schiliro G. Acute neurotoxicity in children with B-lineage acute lymphoblastic leukemia (B-ALL) treated with intermediate risk protocols. Med Pediatr Oncol. 2000;35(5):449-55.

Akut lenfoblastik lösemili çocuklarda nörolojik komplikasyonların ve prognozun değerlendirilmesi

Year 2023, Volume: 28 Issue: 2, 149 - 158, 23.05.2023
https://doi.org/10.21673/anadoluklin.1201526

Abstract

Amaç: Bu çalışmada, akut lenfoblastik lösemi (ALL) tanısıyla tedavi edilmiş çocuk hastaların tedavi esnasında görülen nörolojik komplikasyonların değerlendirilmesi, tanıda ve tedavide nörolojik komplikasyon görülme risk faktörlerinin saptanması ve nörolojik komplikasyonların prognoza etkisinin değerlendirilmesi amaçlanmıştır.

Yöntemler: Çalışmamızda kliniğimizce Ocak 2006 ile Aralık 2011 tarihleri arasında 18 yaş altı ALL tanısı almış ve Berlin Frankfurt Münster (BFM) TR ALL-2000 kemoterapi protokolü uygulanmış olan hastalar, hastane dosya ve kayıt sisteminden geriye dönük incelenmiştir. Çalışmaya dâhil edilen 200 hastanın 6’sı ilk tanıda merkezi sinir sistemi tutulumu olması nedeniyle çalışma dışı bırakıldı. Yüz doksan dört hastanın demografik, klinik, laboratuvar, radyolojik ve nörolojik bulguları değerlendirmeye alındı. Nörolojik komplikasyon görülen olgularla görülmeyen olgular iki gruba ayrılıp cinsiyet, yaş, laboratuvar, tedavi, sağ kalım ve relaps açısından kıyaslandı.

Bulgular: İlk tanıda merkezi sinir sistemi tutulumu olmayan 194 hastanın 28’inde tedavi esnasında nörolojik komplikasyon görüldü. En sık saptanan nörolojik komplikasyon konvülzyondu (%7,7). Nörolojik komplikasyon gelişen hastalarda erkeklerin çoğunlukta olduğu görülmekle birlikte, cinsiyet ve yaş ile nörolojik komplikasyon gelişimi açısından istatistiksel anlamlı ilişki saptanmadı. (p<0,05) Nörolojik komplikasyon görülen hastalarda ilk tanıda lökosit değerlerinin yüksek olduğu ve lökosit yüksekliğinin nörolojik komplikasyon riskini arttırdığı görüldü. Nörolojik komplikasyon görülen hastaların sağ kalım yüzdesinin daha düşük olduğu görülmesine rağmen bu iki grup arasında sağ kalım oranları karşılaştırıldığında istatiksel anlamlı farklılık bulunmadı. (p>0,05)

Sonuç: Çocukluk çağı ALL’sinde kötü bir prognostik faktör olduğu bilinen tanıdaki lökosit sayısının yüksekliğinin, tedavi esnasında görülebilecek nörolojik komplikasyonların habercisi olabileceği akılda tutulmalıdır.

References

  • Karbuz A, Yaralı N, Işık P, Bay A, Kara A, Tunç B. Akut lösemi hastalarının demografik özellikleri ve tedavi sırasında görülen komplikasyonları: tek merkez deneyimi. Türkiye Çocuk Hast Derg. 2017;1:19-26
  • Aricò M, Valsecchi MG, Rizzari C, et al. Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy. J Clin Oncol. 2008;26(2):283-9.
  • Chen CY, Zimmerman RA, Faro S, Bilaniuk LT, Chou TY, Molloy PT. Childhood leukemia: central nervous system abnormalities during and after treatment. AJNR Am J Neuroradiol. 1996;17(2):295-310.
  • Gervasini G, Vagace JM. Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia. Front Genet. 2012;3:249.
  • Vagace JM, de la Maya MD, Caceres-Marzal C, Gonzalez de Murillo S, Gervasini G. Central nervous system chemotoxicity during treatment of pediatric acute lymphoblastic leukemia/lymphoma. Crit Rev Oncol Hematol. 2012;84(2):274-86.
  • Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371(9617):1030-43.
  • Bhatia S. Disparities in cancer outcomes: lessons learned from children with cancer. Pediatr Blood Cancer. 2011;56(6):994-1002.
  • Banerjee J, Niinimäki R, Lähteenmäki P, et al. The spectrum of acute central nervous system symptoms during the treatment of childhood acute lymphoblastic leukaemia. Pediatr Blood Cancer. 2020;67(2):e27999.
  • 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.
  • Baytan B, Evim MS, Güler S, Güneş AM, Okan M. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia. Pediatr Neurol. 2015;53(4):312-8.
  • Parasole R, Petruzziello F, Menna G, et al. Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution. Leuk Lymphoma. 2010;51(6):1063-71.
  • Aytac 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.
  • Vora A, Goulden N, Wade R, et al. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial. Lancet Oncol. 2013;14(3):199-209.
  • Schmidt K, Schulz AS, Debatin KM, Friedrich W, Classen CF. CNS complications in children receiving chemotherapy or hematopoietic stem cell transplantation: retrospective analysis and clinical study of survivors. Pediatr Blood Cancer. 2008;50(2):331-6.
  • Mahoney DH Jr, Shuster JJ, Nitschke R, et al. Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy - a Pediatric Oncology Group study. J Clin Oncol. 1998;16(5):1712-22.
  • Anastasopoulou S, Heyman M, Eriksson MA, et al. Seizures during treatment of childhood acute lymphoblastic leukemia: A population-based cohort study. Eur J Paediatr Neurol. 2020;27:72-7.
  • Taylor OA, Brown AL , Brackett J, et al. Disparities in neurotoxicity risk and outcomes among pediatric acute lymphoblastic leukemia patients. Clin Cancer Res. 2018;24(20):5012-7.
  • Rahman AT, Mannan MA, Sadeque S. Acute and long-term neurological complications in children with acute lymphoblastic leukemia. Bangladesh Med Res Counc Bull. 2008;34(3):90-3.
  • Reddick WE, Glass JO, Helton KJ, et al. Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol. 2005;26(5):1263-9.
  • Kuskonmaz B, Unal S, Gumruk F, Cetin M, Tuncer AM, Gurgey A. The neurologic complications in pediatric acute lymphoblastic leukemia patients excluding leukemic infiltration. Leuk Res. 2006;30(5):537-41.
  • Apak H, Ekici B, Albayram S, et al. The impact of low dose methotrexate on cerebral complications in acute lymphoblastic leukemia treatment. Turk Arch Pediatr. 2009;44(2):62-7.
  • Dufourg MN, Landman-Parker J, Auclerc MF, et al. Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children. Leukemia. 2007;21(2):238-47.
  • Rubnitz JE, Relling MV, Harrison PL, et al. Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia. Leukemia 1998;12(8):1176-81.
  • Fisher MJ, Khademian ZP, Simon EM, Zimmerman RA, Bilaniuk LT. Diffusion-weighted MR imaging of early methotrexate-related neurotoxicity in children. AJNR Am J Neuroradiol. 2005;26(7):1686-9.
  • Lee AC, Li CH, Wong YC. Transient encephalopathy following high-dose methotrexate. Med Pediatr Oncol. 2003;41(1):101.
  • Kim H, Lee JH, Choi SJ, et al. Risk score model for fatal intracranial hemorrhage. Leukemia. 2006;20(5):770-6.
  • Pui CH, Campana D, Pei D, et al. Treatment of childhood acute lymphoblastic leukemia without prophylactic cranial irradiation. N Engl J Med. 2009;360(26):2730-41.
  • Lo Nigro L, Di Cataldo A, Schiliro G. Acute neurotoxicity in children with B-lineage acute lymphoblastic leukemia (B-ALL) treated with intermediate risk protocols. Med Pediatr Oncol. 2000;35(5):449-55.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section ORIGINAL ARTICLE
Authors

Özlem KALAYCIK ŞENGÜL
İstanbul Medemiyet Üniversitesi Göztepe Eğtim ve Araştırma Hastanesi Çocuk Sağlığı ve Hastalıkları Kliniği
0000-0001-9594-5231
Türkiye


Aylin CANBOLAT
İstanbul Medeniyet Üniversitesi Göztepe Eğitim ve Araştırma Hastanesi Çocuk Hematoloji Kliniği
0000-0001-6173-2350
Türkiye


Çetin TİMUR
İstanbul Medeniyet Üniversitesi Göztepe Eğitim ve Araştırma Hastanesi Çocuk Hematoloji Kliniği
0000-0002-5739-3146
Türkiye


Elif KARATOPRAK
İstanbul Medeniyet Üniversitesi Göztepe Eğitim ve Araştırma Hastanesi Çocuk Nöroloji Kliniği
0000-0003-2515-1764
Türkiye


Müferet ERGÜVEN
İstanbul Medeniyet Üniversitesi Göztepe Eğitim ve Araştırma Hastanesi Çocuk Sağlığı ve Hastalıkları Kliniği
0000-0002-3255-1208
Türkiye

Publication Date May 23, 2023
Published in Issue Year 2023 Volume: 28 Issue: 2

Cite

Vancouver Kalaycık Şengül Ö. , Canbolat A. , Timur Ç. , Karatoprak E. , Ergüven M. Akut lenfoblastik lösemili çocuklarda nörolojik komplikasyonların ve prognozun değerlendirilmesi. Anatolian Clinic the Journal of Medical Sciences. 2023; 28(2): 149-158.

13151 This Journal licensed under a CC BY-NC (Creative Commons Attribution-NonCommercial 4.0) International License.