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1.
J Neurooncol ; 145(1): 177-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522324

RESUMO

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. METHODS: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. RESULTS: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. CONCLUSION: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

2.
Acta Neuropathol ; 136(2): 239-253, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29766299

RESUMO

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80% of cases. In the DLGNT-MC-1 group, age at diagnosis was significantly lower (median 5 vs 14 years, p < 0.01) and clinical course less aggressive (5-year OS 100, vs 43% in DLGNT-MC-2). Our study proposes an additional molecular layer to the current histopathological classification of DLGNT, of particular use for cases without typical morphological or radiological characteristics, such as diffuse growth and radiologic leptomeningeal dissemination. Recurrent 1p deletion and MAPK/ERK pathway activation represent diagnostic biomarkers and therapeutic targets, respectively-laying the foundation for future clinical trials with, e.g., MEK inhibitors that may improve the clinical outcome of patients with DLGNT.


Assuntos
Neoplasias Meníngeas/classificação , Neoplasias Meníngeas/genética , Oligodendroglioma/classificação , Oligodendroglioma/genética , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Metilação de DNA/genética , Feminino , Testes Genéticos , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Transdução de Sinais/genética , Transcriptoma , Adulto Jovem
3.
Childs Nerv Syst ; 33(5): 849-852, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28251325

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is an aggressive infiltrative glioma for which no curative therapy is available. Radiation therapy (RT) is the only potentially effective intervention in delaying tumor progression, but only transiently. At progression, re-irradiation is gaining popularity as an effective palliative therapy. However, at second progression, exclusive symptomatic treatment is usually offered. Here we report two patients with DIPG at second progression who were treated with a second re-irradiation course with good response. Importantly, treatment was well tolerated with no irradiation associated acute toxicity identified.


Assuntos
Neoplasias do Tronco Encefálico/radioterapia , Progressão da Doença , Glioma/radioterapia , Reirradiação/métodos , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Glioma/diagnóstico por imagem , Humanos , Masculino
5.
Artigo em Inglês | IBECS | ID: ibc-160159

RESUMO

Introduction: The routine use of a single aerobic bottle for blood culture in pediatric patients has become commonplace, as anaerobic bacteria are not frequently involved in clinically significant infections. The aim of this study was to assess the usefulness of routinely performing anaerobic blood cultures in pediatric oncology patients. Methods: Prospective study was conducted on pediatric (<18 years) patients affected with febrile syndrome after receiving chemotherapy for hematological or solid malignancies. Samples were inoculated into pediatric aerobic and standard anaerobic bottles (BacT/Alert automatic system). Strains were considered clinically significant, or deemed as contaminants, depending on isolation circumstances and clinical criteria. Results: A total of 876 blood cultures from 228 patients were processed during the 21-month study period (January 2014 to September 2015). Baseline diagnosis included 143 solid tumors and 67/18 cases of leukemia/lymphoma. Bacterial growth was detected in 90 (10.2%) blood cultures for 95 different isolates, of which 62 (7.1%)/63 isolates were considered clinically significant. Among the latter, 38 (60.3%) microorganisms grew in both aerobic and anaerobic bottles, 18 (28.6%) only in aerobic bottles, and 7 (11.1%) only in anaerobic bottles. Gram-negative bacilli (33; 52.4%), mainly from the Enterobacteriaceae family, were the most frequently isolated microorganisms. Overall, only 3 out of 90 isolates (3.3%) were strict anaerobes (Propionibacterium acnes), and all of them were deemed contaminants. Conclusion: Strict anaerobes did not cause significant infections in febrile pediatric oncology patients, and anaerobic blood culture bottles offered no additional advantages over aerobic media. Our results suggest that routine blood cultures should be solely processed in aerobic media in this group of patients (AU)


Introducción: En pacientes pediátricos es habitual el procesamiento de hemocultivos únicamente en medio aerobio, debido a la escasa relevancia de los microorganismos anaerobios en la etiología infecciosa habitual. El objetivo de este estudio es valorar la utilidad del uso rutinario del medio de cultivo anaerobio en pacientes oncológicos pediátricos. Métodos: Estudio prospectivo en pacientes pediátricos (<18años) en tratamiento quimioterápico de procesos oncológicos con síndrome febril. Las muestras se inocularon en botellas aerobias pediátricas y anaerobias estándar (sistema automático BacT/Alert). Las cepas aisladas fueron consideradas clínicamente significativas o contaminantes en función de las circunstancias de aislamiento y la clínica del paciente. Resultados: Durante el periodo de estudio (enero 2015-septiembre 2016) se procesaron 876 hemocultivos procedentes de 228 pacientes diagnosticados de tumores sólidos (143) y leucemia/linfoma (67/18). Se detectó crecimiento en 90 (10,2%) hemocultivos y se aislaron 95 cepas, de los cuales 62 (7,1%), correspondientes a 63 cepas, se consideraron clínicamente significativos. Entre estos últimos, 38 (60,3%) microorganismos crecieron en ambas botellas, 18 (28,6%) únicamente en aerobiosis y 7 (11,1%) únicamente en anaerobiosis. Bacilos gram negativos (33; 52,4%), mayoritariamente enterobacterias, fueron los más frecuentemente aislados. Solo 3 (3,3%) de los microorganismos aislados eran anaerobios estrictos (Propionibacterium acnes), y todos ellos fueron considerados contaminantes. Conclusión: Microorganismos anaerobios están raramente involucrados en infecciones en pacientes oncológicos pediátricos, y la utilización de botellas anaerobias no ofrece ninguna ventaja adicional. Según nuestros resultados es suficiente el uso de medio aerobio en el procesamiento de los hemocultivos en este tipo de pacientes (AU)


Assuntos
Humanos , Bactérias Anaeróbias/patogenicidade , Bacteriemia/microbiologia , Neoplasias/complicações , Técnicas Microbiológicas/métodos , Infecções Bacterianas/microbiologia , Estudos Prospectivos
6.
Enferm Infecc Microbiol Clin ; 35(1): 33-36, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27221161

RESUMO

INTRODUCTION: The routine use of a single aerobic bottle for blood culture in pediatric patients has become commonplace, as anaerobic bacteria are not frequently involved in clinically significant infections. The aim of this study was to assess the usefulness of routinely performing anaerobic blood cultures in pediatric oncology patients. METHODS: Prospective study was conducted on pediatric (<18 years) patients affected with febrile syndrome after receiving chemotherapy for hematological or solid malignancies. Samples were inoculated into pediatric aerobic and standard anaerobic bottles (BacT/Alert automatic system). Strains were considered clinically significant, or deemed as contaminants, depending on isolation circumstances and clinical criteria. RESULTS: A total of 876 blood cultures from 228 patients were processed during the 21-month study period (January 2014 to September 2015). Baseline diagnosis included 143 solid tumors and 67/18 cases of leukemia/lymphoma. Bacterial growth was detected in 90 (10.2%) blood cultures for 95 different isolates, of which 62 (7.1%)/63 isolates were considered clinically significant. Among the latter, 38 (60.3%) microorganisms grew in both aerobic and anaerobic bottles, 18 (28.6%) only in aerobic bottles, and 7 (11.1%) only in anaerobic bottles. Gram-negative bacilli (33; 52.4%), mainly from the Enterobacteriaceae family, were the most frequently isolated microorganisms. Overall, only 3 out of 90 isolates (3.3%) were strict anaerobes (Propionibacterium acnes), and all of them were deemed contaminants. CONCLUSION: Strict anaerobes did not cause significant infections in febrile pediatric oncology patients, and anaerobic blood culture bottles offered no additional advantages over aerobic media. Our results suggest that routine blood cultures should be solely processed in aerobic media in this group of patients.


Assuntos
Bactérias Anaeróbias/isolamento & purificação , Técnicas Bacteriológicas , Hemocultura , Neoplasias/microbiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
8.
Neurocir.-Soc. Luso-Esp. Neurocir ; 27(2): 58-66, mar.-abr. 2016. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-150772

RESUMO

Los tumores de plexo coroideo son tumores raros, con un pico de incidencia en los 2 primeros años de vida. La localización más frecuente en niños es el ventrículo lateral, mientras que en adultos es el IV ventrículo. La manifestación clínica más común son los signos y síntomas de hipertensión intracraneal. Histológicamente se clasifican en papiloma de plexo, papiloma atípico de plexo y carcinoma de plexo. Realizamos una revisión de los tumores de plexo coroideo tratados en el Hospital Sant Joan de Déu entre 1980 y 2014. Se han tratado 18 pacientes. Analizamos datos demográficos, clínicos, histológicos, tratamiento recibido y recidivas. El tratamiento de elección es la resección completa, que se acompaña de tratamiento adyuvante en carcinomas. En papilomas atípicos es controvertido el uso de tratamientos adyuvantes, reservándose la radioterapia para las recidivas. Los papilomas tienen un buen pronóstico, mientras que en papilomas atípicos y carcinomas el pronóstico es peor (AU)


Choroid plexus tumours are rare, with a peak incidence in the first two years of life. The most common location is the lateral ventricle in children, while in adults it is the fourth ventricle. The most common clinical manifestation is the signs and symptoms of intracranial hypertension. They are histologically classified as plexus papilloma, atypical plexus papilloma, and plexus carcinoma. A review is presented on choroid plexus tumours treated in the Hospital Sant Joan de Déu between 1980 and 2014. A total of 18 patients have been treated. An analysis was made of the demographic, clinical, histological data, treatment, and recurrences. The treatment of choice is complete resection, accompanied by adjuvant therapy in carcinomas. In atypical papillomas, the use of adjuvant therapies is controversial, reserving radiation therapy for recurrences. Papillomas have a good outcome, whereas atypical papillomas and carcinomas outcome is poor (AU)


Assuntos
Humanos , Masculino , Feminino , Lactente , Neoplasias do Plexo Corióideo/epidemiologia , Papiloma/epidemiologia , Hidrocefalia , Hipertensão Intracraniana/epidemiologia , Neoplasias do Plexo Corióideo/cirurgia , Hospitais Pediátricos/estatística & dados numéricos
9.
Neurocirugia (Astur) ; 27(2): 58-66, 2016.
Artigo em Espanhol | MEDLINE | ID: mdl-26209253

RESUMO

Choroid plexus tumours are rare, with a peak incidence in the first two years of life. The most common location is the lateral ventricle in children, while in adults it is the fourth ventricle. The most common clinical manifestation is the signs and symptoms of intracranial hypertension. They are histologically classified as plexus papilloma, atypical plexus papilloma, and plexus carcinoma. A review is presented on choroid plexus tumours treated in the Hospital Sant Joan de Déu between 1980 and 2014. A total of 18 patients have been treated. An analysis was made of the demographic, clinical, histological data, treatment, and recurrences. The treatment of choice is complete resection, accompanied by adjuvant therapy in carcinomas. In atypical papillomas, the use of adjuvant therapies is controversial, reserving radiation therapy for recurrences. Papillomas have a good outcome, whereas atypical papillomas and carcinomas outcome is poor.


Assuntos
Neoplasias do Plexo Corióideo , Carcinoma/diagnóstico , Carcinoma/terapia , Criança , Pré-Escolar , Neoplasias do Plexo Corióideo/diagnóstico , Neoplasias do Plexo Corióideo/terapia , Terapia Combinada , Feminino , Hospitais , Humanos , Lactente , Masculino , Papiloma do Plexo Corióideo/diagnóstico , Papiloma do Plexo Corióideo/terapia , Estudos Retrospectivos , Espanha
10.
Eur J Pediatr ; 174(8): 1069-76, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25749928

RESUMO

UNLABELLED: Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency associated with an increased risk of malignancy in adulthood, with lymphoma as one of the major causes of death. The aim of this study is to describe those malignancies detected in our cohort of pediatric CVID patients. We reviewed the clinical and laboratory data and the treatments and their outcomes in all pediatric CVID patients from our institution that developed a neoplasia. Four malignancies were diagnosed in three out of 27 pediatric CVID patients. Three malignancies were non-Hodgkin lymphoma (NHL) of B cell origin (mean age at diagnosis: 8 years old), and the remaining was a low-grade astrocytoma. Among NHL, two were mucosa-associated lymphoid tissue (MALT) lymphomas and one was associated with Epstein-Barr virus infection. NHL developed before CVID diagnosis in two patients. CVID patients showed different clinical phenotypes and belonged to different groups according Euroclass and Pediatric classification criteria. CONCLUSIONS: Malignancies, especially lymphoma, may develop in pediatric CVID patients with no previous signs of lymphoid hyperplasia and even before CVID diagnosis. Consequently, strategies for cancer prevention and/or early diagnosis are required in pediatric CVID patients.


Assuntos
Astrocitoma/diagnóstico , Imunodeficiência de Variável Comum/complicações , Linfoma não Hodgkin/diagnóstico , Adolescente , Astrocitoma/etiologia , Astrocitoma/imunologia , Criança , Imunodeficiência de Variável Comum/imunologia , Diagnóstico Precoce , Feminino , Humanos , Incidência , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/imunologia , Masculino , Fenótipo
11.
J Neurooncol ; 113(1): 127-34, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23459995

RESUMO

A multicenter, two stage phase II study, investigated irinotecan plus temozolomide in children with newly diagnosed high grade glioma. The primary endpoint was tumor response during a two-cycle treatment window, confirmed by external review committee. Patients received oral temozolomide 100 mg/(m(2) day) (days 1-5) and intravenous irinotecan 10 mg/(m(2) day) (days 1-5 and 8-12) for two 21-day cycles (three cycles for patients exhibiting objective tumor response). Standard treatment was then administered according to local investigator choice. In total 17 patients were enrolled and treated by local investigators. However, central pathology review found three patients did not have a diagnosis of high grade glioma and another four patients did not have evaluable disease according to independent central radiological review. The primary endpoint was based on the first ten evaluable patients as determined by the external review committee. Recruitment was stopped for futility after there were no complete or partial responses during the two-cycle treatment window in the first ten evaluable patients. Five patients had stable disease, and five progressed. Data for secondary endpoints including; time to tumor progression, time to treatment failure, and overall survival is reported. The safety profile of the treatment showed the combination was tolerable with two patients (11.8 %) having grade three nausea, and one (5.9 %) experiencing a grade four neutropenia, leading to permanent discontinuation from adjuvant treatment. Irinotecan plus temozolomide, although well tolerated did not improve outcome over historical controls in this setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Encefálicas/patologia , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Criança , Pré-Escolar , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Feminino , Glioma/patologia , Humanos , Irinotecano , Masculino , Gradação de Tumores , Temozolomida , Resultado do Tratamento
12.
Rev Neurol ; 54(12): 712-8, 2012 Jun 16.
Artigo em Espanhol | MEDLINE | ID: mdl-22673947

RESUMO

INTRODUCTION. High-dose methotrexate (MTX) has showed to increase the surveillance in children with acute lymphoblastic leukemia and other neoplasms. However, MTX may induce significant neurotoxicity. AIM. To evaluate, in our population of patients who have been treated with MTX, the incidence of neurotoxicity and to describe its main clinical and radiological characteristics. PATIENTS AND METHODS. We retrospectively review the patients who received treatment with systemic high-dose MTX and/or intrathecal MTX between 1994 and 2010. The children who presented clinical o radiological signs of neurotoxicity were reviewed. RESULTS. We identified 284 patients who received high-dose intravenous and/or intrathecal MTX. 9 patients presented neurotoxicity. The median age at diagnosis was 6 years; 6 patients were male. The diagnosis included: 6 acute lymphoblastic leukemia, 2 medulloblastoma and 1 lymphoma. 66% patients presented focal neurological dysfunction, 3 had non-specific symptoms. In 5 patients the symptomatology started the first 14 days after the MTX administration. 8 patients had complete clinical resolution, but only one presented neurological long term effects. All the patients except one showed signs of acute leukoencephalopathy in the brain MR study. These alterations resolved one year later in 3 patients; in the other patients the MR alterations persisted. The neurotoxicity management was corticosteroid, folinic acid, aminophylline and dextromethorphan. CONCLUSION. The MTX neurotoxicity it can present as acute or chronic. It has a wide clinical spectrum, ranging from sub-clinical manifestations with complete recovery to a chronic and progressive encephalopathy.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Metotrexato/efeitos adversos , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Estudos Retrospectivos
13.
Rev. neurol. (Ed. impr.) ; 54(12): 712-718, 16 jun., 2012. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-101742

RESUMO

Introducción. El metotrexato (MTX) en altas dosis ha demostrado aumentar la supervivencia en pacientes con diagnóstico de leucemia linfoblástica aguda y otro tipo de neoplasias. Sin embargo, es un fármaco neurotóxico. Objetivo. Evaluar, en nuestra población de pacientes tratados con MTX, la incidencia de neurotoxicidad y sus características clinicorradiológicas. Pacientes y métodos. Estudio retrospectivo de pacientes que recibieron tratamiento con MTX endovenoso en altas dosis o intratecal entre los años 1994-2010. Se recogen los casos que presentaron clínica o signos radiológicos de neurotoxicidad. Resultados. Un total de 284 pacientes recibió MTX endovenoso en altas dosis o intratecal. Nueve pacientes (3,1%) presentaron neurotoxicidad. Edad media al diagnóstico: 6 años; seis eran de sexo masculino. Sus diagnósticos de base fueron: en seis leucemia linfoblástica aguda, en dos meduloblastoma y en uno linfoma. Un 66% de los pacientes presentó síntomas neurológicos focales, y tres, síntomas inespecíficos. En cinco pacientes (55%) la clínica se inició dentro los primeros 14 días tras la administración de MTX. Ocho pacientes tuvieron una recuperación clínica completa; uno presentó secuelas neurológicas. Todos los pacientes excepto uno mostraban signos de leucoencefalopatía en la resonancia magnética cerebral. Estos hallazgos se normalizaron al año en tres pacientes; el resto mostraba persistencia de las lesiones. El tratamiento de la neurotoxicidad se basó en corticoides endovenosos (n = 2), ácido fólico (n = 2) o aminofilina y dextrometorfano (n = 1). Conclusiones. La neurotoxicidad por MTX tiene un espectro clínico amplio, con aparición precoz o tardía; puede cursar de forma subclínica o ser una ncefalopatía progresiva y grave (AU)


Introduction. High-dose methotrexate (MTX) has showed to increase the surveillance in children with acute lymphoblastic leukemia and other neoplasms. However, MTX may induce significant neurotoxicity. Aim. To evaluate, in our population of patients who have been treated with MTX, the incidence of neurotoxicity and to describe its main clinical and radiological characteristics. Patients and methods. We retrospectively review the patients who received treatment with systemic high-dose MTX and/or intrathecal MTX between 1994 and 2010. The children who presented clinical o radiological signs of neurotoxicity were reviewed. Results. We identified 284 patients who received high-dose intravenous and/or intrathecal MTX. 9 patients presented neurotoxicity. The median age at diagnosis was 6 years; 6 patients were male. The diagnosis included: 6 acute lymphoblastic leukemia, 2 medulloblastoma and 1 lymphoma. 66% patients presented focal neurological dysfunction, 3 had nonspecific symptoms. In 5 patients the symptomatology started the first 14 days after the MTX administration. 8 patients had complete clinical resolution, but only one presented neurological long term effects. All the patients except one showed signs of acute leukoencephalopathy in the brain MR study. These alterations resolved one year later in 3 patients; in the other patients the MR alterations persisted. The neurotoxicity management was corticosteroid, folinic acid, aminophylline and dextromethorphan. Conclusion. The MTX neurotoxicity it can present as acute or chronic. It has a wide clinical spectrum, ranging from subclinical manifestations with complete recovery to a chronic and progressive encephalopathy (AU)


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Metotrexato/toxicidade , Síndromes Neurotóxicas/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucoencefalopatias/tratamento farmacológico , Estudos Retrospectivos , Antineoplásicos/toxicidade , Corticosteroides/uso terapêutico
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