RESUMO
PURPOSE: To assess the efficacy and safety of liposomal cytarabine in the treatment of de novo and relapsed leptomeningeal involvement in children with primary CNS tumours. METHODS: Data from clinical charts were entered into a database for consecutive unselected patients (n=20) from nine Spanish centres. Diagnosis of leptomeningeal involvement was confirmed by cytology, MRI and/or CT scan. The dose of liposomal cytarabine used varied from 20 to 50 mg, by age. RESULTS: There were 8 females and 12 males, mean age 7.3 years (range 8 months to 18 years). The tumours were: 10 medulloblastomas, 4 ependymomas, 3 primitive neuroectodermal tumours and 3 other tumours. Fourteen had undergone previous chemotherapy and 12 radiotherapy. Nine received concurrent chemotherapy and 2 concurrent radiotherapy. Median follow-up was 244.5 days (range 12- 869). Patients received a median of 5 doses (range 1-9) of liposomal cytarabine. A neurological response (complete or partial) was seen in 11/19 (58%) and a cytological response in 7/10 (64%). Median time to neurological progression exceeded 180 days (range 12-869). Adverse effects were reported in 11/20 patients, but none was grade IV. DISCUSSION: Liposomal cytarabine was well tolerated and efficacious in this patient group, but prospective randomised trials are needed.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Citarabina/uso terapêutico , Lipossomos/uso terapêutico , Neoplasias Meníngeas/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Segurança do Paciente , Qualidade de Vida , Espanha , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Recent advances in treatment for childhood acute lymphoblastic leukaemia (ALL) have significantly increased outcome. High-dose methotrexate (MTX) is the most commonly used regimen during the consolidation period, but the optimal dose remains to be defined. We investigated the usefulness of the MTHFR genotype to increase the MTX dosage in the consolidation phase in 141 childhood ALL patients enrolled in the ALL/SHOP-2005 protocol. We also investigated the pharmacogenetic role of polymorphisms in genes involved in MTX metabolism on therapy-related toxicity and survival. Patients with a favourable MTHFR genotype (normal enzymatic activity) treated with MTX doses of 5 g m⻲ had a significantly lower risk of suffering an event than patients with an unfavourable MTHFR genotype (reduced enzymatic activity) that were treated with the classical MTX dose of 3 g m⻲ (P=0.012). Our results indicate that analysis of the MTHFR genotype is a useful tool to optimise MTX therapy in childhood patients with ALL.
Assuntos
Metotrexato , Metilenotetra-Hidrofolato Redutase (NADPH2) , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/farmacocinética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Farmacogenética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
Medulloblastoma is the most common infratentorial malignant tumour under 15 years of age. In recent protocols, the patients are stratified for treatment in standard risk or high risk, according to the clinical variables as age, localized or disseminated disease, degree of surgical resection and more recently expected biological behaviour based on retrospective and prospective studies of former samples analyzed. The objectives for future treatments are reduce morbidity without jeopardizing survival.
Assuntos
Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/terapia , Meduloblastoma/patologia , Meduloblastoma/terapia , Antineoplásicos/uso terapêutico , Criança , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Procedimentos Neurocirúrgicos , RadioterapiaRESUMO
BACKGROUND: Stage 4 and MYCN amplified (MNA) neuroblastoma in children have a poor prognosis. Our aim was to increase initial and long-term response in this population. PROCEDURE: High-risk children were studied according to the International Neuroblastoma Staging System, then treated with high-dose cyclophosphamide and high-dose carboplatin, followed by surgery and autologous stem cell transplant or maintenance chemotherapy. RESULTS: From June 1992 to December 1998, 83 children were admitted in the study (72 stage 4> 1 year, 5 stage 4 MNA infants, and 6 MNA stage 3 children); tumor tissue was obtained from 73, MYCN was performed in 65, being amplified in 21 (32%). Induction chemotherapy was administered in the expected time in 35% of patients. Its toxicity was mainly hematologic followed by infections, and there were 3 chemotherapy-related deaths. Delayed surgery was performed on 60 patients with complete or >90% resection in 80% of cases. Chemotherapy plus surgery produced some response in 90% of patients, 53% were in CR/VGPR; 49 children received autologous SCT, and 16 received maintenance chemotherapy for 9 months. Follow-up ranges are 1-87 months, mean 30 months. S and EFS at 4 years are 0.33 (SD 0.02). CONCLUSIONS: High-dose cyclophosphamide and high-dose carboplatin are effective in the initial treatment of neuroblastoma; combined with surgery they produce some response in most patients. Nevertheless, the CR/VGPR rate reaches only 53%. Survival time has also been prolonged but most patients relapse with metastases.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Neuroblastoma/tratamento farmacológico , Neuroblastoma/mortalidade , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Neuroblastoma/patologia , Neuroblastoma/cirurgia , Espanha , Análise de Sobrevida , Sobreviventes , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
Mutation analysis of retinoblastoma is considered important for genetic counseling purposes, as well as for understanding the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of an analysis of 43 hereditary retinoblastoma Spanish patients and kindred, using direct PCR sequencing, we have observed 29 mutations; most of them (62%) have not been reported previously. Of the mutations, 69% correspond to nonsense mutations (mainly CpG transitions) and frameshifts, with the expected outcome of a truncated Rb protein that lacks the functional pocket domains and tail. The remainder corresponds to splicing mutations, most of them (62%) targeted to invariant nucleotides, with the predicted consequence of out of frame exon skipping. Two of the splicing mutations in our study were found associated to families with a low-penetrance phenotype. Additionally, most of the mutations affecting splice junctions corresponded to retinoblastoma cases of either sporadic or hereditary nature with delayed onset (32 months on average). In contrast, most of the nonsense and frameshift mutations are associated with an early age at diagnosis (8.7 months on average). These differences are discussed in the context of the relationships between genotype and low expressivity phenotype. The differences in the spectrum of RB1 mutations found in this and other European surveys are also discussed in the context of alternate DNA methylation and mismatch repair phenotypes.
Assuntos
Mutação em Linhagem Germinativa/genética , Retinoblastoma/genética , Retinoblastoma/fisiopatologia , Idade de Início , Processamento Alternativo/genética , Sequência de Bases , Pré-Escolar , Códon sem Sentido/genética , Metilação de DNA , Análise Mutacional de DNA , Reparo do DNA , Éxons/genética , Feminino , Mutação da Fase de Leitura/genética , Testes Genéticos , Genótipo , Humanos , Lactente , Íntrons/genética , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Regiões Promotoras Genéticas/genética , Sítios de Splice de RNA/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Retinoblastoma/química , Retinoblastoma/epidemiologia , EspanhaAssuntos
Polimorfismo de Nucleotídeo Único/genética , Proteína do Retinoblastoma/genética , Retinoblastoma/genética , Análise Mutacional de DNA , Éxons , Frequência do Gene , Humanos , Íntrons , Dados de Sequência Molecular , Mutação de Sentido Incorreto/genética , Fases de Leitura Aberta/genética , Espanha , População Branca/genéticaRESUMO
BACKGROUND: Prognosis of relapsed and refractory neuroblastoma is uniformly fatal; new therapeutic approaches are needed. PROCEDURE: Relapsed and refractory neuroblastoma patients were treated with continuous infusion chemotherapy combined with MIBG. RESULTS: Over 4 years, 35 heavily pretreated patients were registered, 29 with bone or/and bone marrow metastases. Grade 3 or 4 hematologic toxicity was frequent, without toxic deaths. Sixteen patients responded. The probability of 5-year overall survival was 0.19. CONCLUSIONS: This approach is feasible and toxicity manageable; it rescued some patients and prolonged their survival. It merits assay in newly diagnosed high-risk neuroblastoma patients.
Assuntos
3-Iodobenzilguanidina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/secundário , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Neuroblastoma/mortalidade , Taxa de SobrevidaRESUMO
The aim of this study was to classify prospectively a series of neuroblastoma tumours according to the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) and to evaluate the difficulties and pitfalls involved in a multicentre setting. Each hospital provided their data for central review. The surgical procedures and their complications were reported. Kaplan-Meier estimates of survival and event-free survival were calculated according to stage and response to therapy. From June 1992 to December 1996, 194 patients were included in the study, with a mean age of 2 years. Initial studies were performed according to INSS recommendations without major problems. INSS stage was correctly applied to all patients except for 9 (95%). Post-operative complications were observed in 15 patients (8.3%). Response to therapy (INRC) was studied in 63 stage 4 patients, 11 of whom were not classified correctly (17%). Differences in survival according to stage (INSS) and group of response to therapy (INRC) were statistically significant (P < 0.001). In conclusion the INSS was easy to use and separated different prognostic groups. Surgical complications and mortality did not increase in this series because of using the INSS. The feasibility of INRC was evaluated in a small series of stage 4 patients and the designation of response was problematic in a relatively high proportion of cases. The prognostic value of the different responses was highly significant, but less informative than had been hoped for.
Assuntos
Estadiamento de Neoplasias/métodos , Neuroblastoma/patologia , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Crista Neural , Estudos ProspectivosRESUMO
Varicella vaccine has shown its efficacy to prevent the disease and complications in healthy and immunodeficient children. In this article the authors evaluate the immunologic status of acute lymphoblastic leukaemia at diagnosis and at follow up and the development of chickenpox and/or herpes zoster. Children with negative serology and continuous complete remission of acute lymphoblastic leukaemia for one year were vaccinated. Of 71 children diagnosed of acute lymphoblastic leukaemia from 1983 to 1996, 25 received the vaccine and seroconversion was obtained in 76% after one dose and 92% after the second dose. Vaccine tolerance was adequate. The incidence of herpes zoster infection was decreased in vaccinated children during chemotherapy compared to the wild-virus infected ones. Nowadays that vaccine for healthy children is recommended, we consider a priority to protect from chickenpox the children affected by leukaemia that are in continuous complete remission of the disease.
Assuntos
Vacina contra Varicela/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Varicela/prevenção & controle , Vacina contra Varicela/administração & dosagem , Criança , Pré-Escolar , Feminino , Herpes Zoster , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de RemissãoRESUMO
Interferon-alpha (IFN-alpha) is a biological response modifier with antiviral and tumoral effect that is used in the treatment of chronic myelogenous leukemias. Adverse effects are well documented and cardiovascular disturbances mostly include hypotension and tachycardia and rarely cardiomyopathy. We report on an infant with chronic myelomonocytic leukemia (CML) diagnosed at 3 months of age who was treated with increasing IFN-alpha dosage (2.5-5.5 million U/m2/day) given subcutaneously for 7.5 months. At that age, he presented anorexia, general malaise, and nocturnal sweating for about a week, followed by respiratory distress and tachycardia. Diagnosis of congestive heart failure was suspected and documented by cardiomegaly and echographic changes of left ventricular dilated cardiomyopathy, with a 40% left ventricular ejection fraction (EF) and 20% fractional shortening (FS). He was treated with digoxin, furosemide, and angiotensin converting inhibitors, and IFN-alpha was discontinued. Progressive improvement of cardiac function was observed within 7 months of the events with normalization of the echocardiographic findings (EF 60%, FS 31%). We should emphasize the possibility of severe and reversible cardiac toxicity of IFN-alpha in infancy.
Assuntos
Antineoplásicos/efeitos adversos , Cardiomiopatia Dilatada/induzido quimicamente , Interferon-alfa/efeitos adversos , Antineoplásicos/uso terapêutico , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiotônicos/uso terapêutico , Relação Dose-Resposta a Droga , Ecocardiografia , Seguimentos , Hemodinâmica/efeitos dos fármacos , Humanos , Lactente , Interferon-alfa/uso terapêutico , Leucemia Mielomonocítica Crônica/diagnóstico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Masculino , Resultado do TratamentoRESUMO
Although the acute renal toxicity of cisplatin has been well documented, long-term follow-up studies in cisplatin-treated children are scanty. We have evaluated the incidence and characteristics of both acute and chronic nephrotoxicity in 22 children (median age 8 years) treated with cisplatin as part of different chemotherapeutic protocols. All patients exhibited a significant and progressive decrease in plasma magnesium (Mg) values soon after cisplatin administration. Magnesiuria also increased immediately after therapy. Hypomagnesemia (plasma Mg < 1.4 mg/dl) occurred in 10 patients and it was dose-dependent. Minimal and mean cumulated doses inducing hypomagnesemia were 300 and 500 mg/m2, respectively. In 18 children we followed renal function prospectively for a mean time of 2.3 years after arrest of cisplatin therapy. Chronic hypomagnesemia and moderate elevation of plasma creatinine were observed in 6 children, hypocalciuria in 5 children, and hypokalemia in 1 child. Presence of hypomagnesemia was unrelated to the total dose received or the time elapsed since cisplatin therapy. Renal function studies, performed in the 6 children with chronic hypomagnesemia, revealed different degrees of impairment in Mg reabsorption. The functional characteristics of chronic cisplatin nephrotoxicity found in the present series-contrary to prior reports-are not comparable to those present in the inherited Gitelman's syndrome.
Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Homeostase/efeitos dos fármacos , Rim/fisiopatologia , Magnésio/metabolismo , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Cisplatino/uso terapêutico , Feminino , Humanos , Lactente , Rim/efeitos dos fármacos , Masculino , Estudos ProspectivosRESUMO
UNLABELLED: Fetal hydrops associated with neonatal tumours is an uncommon occurrence. The diagnosis can be established prenatally by ultrasound examination. The treatment of choice is surgery which may be curative. We report the case of a male born at 32 weeks gestation who presented with severe hydrops fetalis and a thoracic mass. The child could not be operated upon because of rapid clinical deterioration. The autopsy findings confirmed the diagnosis of congenital fibrosarcoma. This is, to our knowledge, the first case of hydrops fetalis associated with fibrosarcoma. CONCLUSION: The association of hydrops fetalis and fibrosarcoma is an exceptional observation but can be added to the long list of differential diagnoses of non-immune hydrops.
Assuntos
Fibrossarcoma/congênito , Hidropisia Fetal/complicações , Neoplasias Torácicas/congênito , Evolução Fatal , Fibrossarcoma/complicações , Fibrossarcoma/patologia , Humanos , Recém-Nascido , Masculino , Neoplasias Torácicas/complicações , Neoplasias Torácicas/patologiaRESUMO
Cerebral and meningeal involvement in patients with primary extracranial neuroblastoma (NB) is unusual although it is generally present in disseminated disease. The intensification of chemotherapy that has prolonged survival in these children has changed the pattern of relapse presentation, as occurs with isolated central nervous system (CNS) disease. We report 4 patients with secondary CNS metastases. Three infants of 16, 14, and 10 months of age, diagnosed with primary abdominal NB stage 4, presented neuromeningeal metastases during maintenance chemotherapy with seizures and cranial hypertension as the first manifestation. Another 8-year-old patient diagnosed with NB stage 3 presented local relapse with later neuromeningeal metastases. All died in the following 3 months. The possibility of CNS relapse in patients with NB should be considered when neurological symptoms and signs appear. These new relapse forms overshadow the prognosis of these children.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Meníngeas/secundário , Neuroblastoma/secundário , Neoplasias Abdominais/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Criança , Feminino , Humanos , Lactente , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patologia , Neuroblastoma/diagnóstico , Neuroblastoma/patologia , PrognósticoRESUMO
A child with AIDS is presented who developed L1-ALL while being treated for L3-AL. After achievement of complete remission of the former, he suffered a relapse with L3 morphology. Although the possibilities of a shift in both the morphology and the immunophenotype of ALL in relapse are well known, the rarity of L1-ALL in association with AIDS is stressed by the authors, along with the factors related with the morphologic and phenotypic changes shown by these patients.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Linfoma de Burkitt/complicações , Segunda Neoplasia Primária , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Linfoma de Burkitt/sangue , Linfoma de Burkitt/patologia , Pré-Escolar , Evolução Fatal , Humanos , Imunofenotipagem , Masculino , Segunda Neoplasia Primária/sangue , Segunda Neoplasia Primária/patologia , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Zidovudina/uso terapêuticoRESUMO
The Spanish Neuroblastoma Study Group has conducted a study on advanced neuroblastoma (N-I-87), which included 33 stage III and 60 stage IV neuroblastoma children more than 1 year of age, enrolled between October 1987 and April 1992. They were staged according to Evans and treated with induction chemotherapy (IC) consisting of 3 courses of cyclophosphamide-doxorubicin alternating with 3 of high-dose cisplatin-teniposide. Evaluation after IC and surgery demonstrated an overall response rate of 88% for stage III and 69% for stage IV. In the latter, complete responses and good partial responses were 33 and 14%, respectively. After surgery, children received maintenance chemotherapy (all stage III except 2 and 30 stage IV) or autologous bone marrow transplantation (ABMT) (11 stage IV), the distribution was not randomised. Probability of survival at 5 years was 0.60 +/- 0.12 for stage III and 0.24 +/- 0.07 for stage IV. A significant difference in survival at 5 years was found between "good responders" and "non-responders" to initial chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neuroblastoma/tratamento farmacológico , Adolescente , Transplante de Medula Óssea , Quimioterapia Adjuvante , Criança , Pré-Escolar , Humanos , Lactente , Estadiamento de Neoplasias , Neuroblastoma/patologia , Neuroblastoma/cirurgia , Taxa de SobrevidaRESUMO
The authors reviewed 92 patients diagnosed as ALL. Age range was 1 to 12 years (x = 5 years), 50 males and 42 females. The patients were classified as high risk, intermediate and low risk according to the following prognostic factors: sex, age at diagnosis, visceromegaly, adenopathy, initial WBC, HB, immunoglobulins, and platelets, FAB morphological classification, and bone marrow response to initial therapy, immunological markers, CNS infiltration and mediastinal mass. The previous factors were analyzed individually and also the results obtained with each risk group according to the treatment applied.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/classificação , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prognóstico , Fatores de RiscoRESUMO
Eighteen cases of histiocytosis X are presented and prognostic factors, such as localized or disseminated disease, organ dysfunction and age, are analyzed in relation to results of therapy. A new classification of childhood histiocytosis X, based on prognostic factors, seems to be justified.
Assuntos
Histiocitose de Células de Langerhans , Fatores Etários , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Histiocitose de Células de Langerhans/classificação , Histiocitose de Células de Langerhans/complicações , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/mortalidade , Humanos , Lactente , Masculino , Prognóstico , RadiografiaRESUMO
Paciente con antecedentes de enfermedad tuberculosa bilateral cavitariade predominio izquierdo que realiza tratamiento médico con tuberuclosis de preimera y segunda línea en los años 1974 a 1979. Se consideran imágenes residuales, dos imágenes cavitarias localizadas en los segmentos apicales de ambos lóbulos superiores. A partir de octubre de 1977 se inicia sintomatología de hemoptisis y espectoración hemoptoica en repetidas oportunidades. El 9 de noviembre de 1977 se diagnostica aspergillosis, razón por la que es intervenida quirurgicamente en fecha 10 de enero de 1980 de neumoneotomía, comprobándose histopatológicamente el diagnóstico pre-operatorio. Durante estos tres años el estado bronco-pulmonaar es satisfaactorio y se considera que se consiguió éxito con el tratamiento médico quirúrgico.