Palabras clave
síndrome
pediatría
metotrexate
neurotoxicidad
Cómo citar
Resumen
Se describe el caso de un paciente pediátrico con leucemia linfoblástica aguda T (LLA-T) que durante su tratamiento presenta síntomas neurológicos como efecto adverso asociado a la quimioterapia.
Se discuten los posibles diagnósticos diferenciales, diagnóstico y conducta terapéutica a seguir.
Citas
Pui, C.-H. et al. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J. Clin. Oncol. 33, 2938–2948 (2015).
Millan, N. C. et al. Acute and sub-acute neurological toxicity in children treated for acute lymphoblastic leukemia. Leuk. Res. 65, 86–93 (2018).
Banerjee, J. et al. The spectrum of acute central nervous system symptoms during the treatment of childhood acute lymphoblastic leukaemia. Pediatr. Blood Cancer 67, e27999 (2020).
Parasole, R. et al. Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution. Leukemia & Lymphoma vol. 51 1063–1071 (2010).
Baytan, B., Evim, M. S., Güler, S., Güneş, A. M. & Okan, M. Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic Leukemia. Pediatr. Neurol. 53, 312–318 (2015).
Mateos, M. K. et al. Methotrexate-related central neurotoxicity: clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemia. Haematologica 107, 635–643 (2022).
Rubnitz, J. E. et al. Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia. Leukemia 12, 1176–1181 (1998).
Bhojwani, D. et al. Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia. J. Clin. Oncol. 32, 949–959 (2014).
Schmiegelow, K. et al. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus. Lancet Oncol. 17, e231–e239 (2016).
Kim, S. J. et al. Predisposing factors of posterior reversible encephalopathy syndrome in acute childhood leukemia. Pediatr. Neurol. 47, 436–442 (2012).
Anastasopoulou, S. et al. Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia: Clinical characteristics, risk factors, course, and outcome of disease. Pediatr. Blood Cancer 66, e27594 (2019).
Granata, G. et al. Posterior reversible encephalopathy syndrome--Insight into pathogenesis, clinical variants and treatment approaches. Autoimmun. Rev. 14, 830–836 (2015).
Ghali, M. G. Z., Davanzo, J., Leo, M. & Rizk, E. Posterior reversible encephalopathy syndrome in pediatric patients: pathophysiology, diagnosis, and management. Leuk. Lymphoma 60, 2365–2372 (2019).
Hafez, H. A. et al. Patterns, risk factors and outcome predictors of posterior reversible encephalopathy syndrome in pediatric cancer patients. Leuk. Lymphoma 62, 462–468 (2021).
Cordelli, D. M. et al. Posterior Reversible Encephalopathy Syndrome in infants and young children. Eur. J. Paediatr. Neurol. 30, 128–133 (2021).
McKinney, A. M. et al. Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am. J. Roentgenol. 189, 904–912 (2007).
Fugate, J. E. & Rabinstein, A. A. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 14, 914–925 (2015).
Ni, J. et al. The clinical and radiological spectrum of posterior reversible encephalopathy syndrome: a retrospective series of 24 patients. J. Neuroimaging 21, 219–224 (2011).
Bond, J. et al. ‘Stroke-like syndrome’ caused by intrathecal methotrexate in patients treated during the UKALL 2003 trial. Leukemia vol. 27 954–956 (2013).
Cole, P. D. et al. Folate homeostasis in cerebrospinal fluid during therapy for acute lymphoblastic leukemia. Pediatr. Neurol. 40, 34–41 (2009).
Kishi, S. et al. Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia. J. Clin. Oncol. 21, 3084–3091 (2003).
Quinn, C. T., Griener, J. C., Bottiglieri, T., Arning, E. & Winick, N. J. Effects of Intraventricular Methotrexate on Folate, Adenosine, and Homocysteine Metabolism in Cerebrospinal Fluid. Journal of Pediatric Hematology/Oncology vol. 26 386–388 (2004).
Quinn, C. T. et al. Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer. Journal of Clinical Oncology vol. 15 2800–2806 (1997).
Taylor, O. A. et al. Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients. Clinical Cancer Research vol. 24 5012–5017 (2018).
Bhojwani, D., Bansal, R. & Wayne, A. S. Managing therapy-associated neurotoxicity in children with ALL. Hematology vol. 2021 376–383 (2021).
Watanabe, K. et al. Characteristics of methotrexate-induced stroke-like neurotoxicity. International Journal of Hematology vol. 108 630–636 (2018).
Rollins, N., Winick, N., Bash, R. & Booth, T. Acute methotrexate neurotoxicity: findings on diffusion-weighted imaging and correlation with clinical outcome. AJNR Am. J. Neuroradiol. 25, 1688–1695 (2004).
Athale, U. H. & Chan, A. K. C. Thrombosis in children with acute lymphoblastic leukemia. Thrombosis Research vol. 111 125–131 (2003).
Nowak-Göttl, U., Kenet, G. & Mitchell, L. G. Thrombosis in childhood acute lymphoblastic leukaemia: epidemiology, aetiology, diagnosis, prevention and treatment. Best Practice & Research Clinical Haematology vol. 22 103–114 (2009).
Caruso, V. et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood 108, 2216–2222 (2006).
Kirkham, F. J. Stroke in childhood. Arch. Dis. Child. 81, 85–89 (1999).
Santoro, N. et al. Ischemic Stroke in Children Treated for Acute Lymphoblastic Leukemia. Journal of Pediatric Hematology/Oncology vol. 27 153–157 (2005).
Qureshi, A., Mitchell, C., Richards, S., Vora, A. & Goulden, N. Asparaginase-related venous thrombosis in UKALL 2003- re-exposure to asparaginase is feasible and safe. British Journal of Haematology vol. 149 410–413 (2010).
Musgrave, K. M. et al. Cerebral sinovenous thrombosis in children and young adults with acute lymphoblastic leukaemia - a cohort study from the United Kingdom. British Journal of Haematology vol. 179 667–669 (2017).
Ranta, S. et al. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology. British Journal of Haematology vol. 168 547–552 (2015).
Rank, C. U. et al. Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years. Blood 131, 2475–2484 (2018).
Bianchi, D., Maeder, P., Bogousslavsky, J., Schnyder, P. & Meuli, R. A. Diagnosis of cerebral venous thrombosis with routine magnetic resonance: an update. Eur. Neurol. 40, 179–190 (1998).
Badke, C. et al. Rechallenging With Intrathecal Methotrexate After Developing Subacute Neurotoxicity in Children With Hematologic Malignancies. Pediatr. Blood Cancer 63, 723–726 (2016).
Mahoney, D. H., Jr 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. 16, 1712–1722 (1998).
Cohen, I. J. Neurotoxicity after high-dose methotrexate (MTX) is adequately explained by insufficient folinic acid rescue. Cancer Chemotherapy and Pharmacology vol. 79 1057–1065 (2017).
Todo el material publicado en la revista Hematología (versión electrónica y versión impresa), será cedido a la Sociedad Argentina de Hematología. De conformidad con la ley de derecho de autor (ley 11723) se les enviara a los autores de cada trabajo aceptado formulario de cesión de derechos de autor que deberá ser firmado por todos los autores antes de la publicación. Los autores deberán retener una copia del original pues la revista, no acepta responsabilidad por daños o pérdidas del material enviado. Los autores deberán remitir una versión electrónica al correo: revista@sah.org.ar