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1.
Ann Oncol ; 35(6): 559-568, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38142939

RESUMO

BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.


Assuntos
Biomarcadores Tumorais , Neoplasias Ósseas , DNA Tumoral Circulante , Osteossarcoma , Humanos , Osteossarcoma/genética , Osteossarcoma/sangue , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Osteossarcoma/mortalidade , Osteossarcoma/diagnóstico , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Masculino , Feminino , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/sangue , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/mortalidade , Adulto , Adolescente , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Estudos Prospectivos , Adulto Jovem , Criança , Variações do Número de Cópias de DNA , Gradação de Tumores , Pessoa de Meia-Idade , Sequenciamento Completo do Genoma , Intervalo Livre de Progressão
2.
J Immunother Cancer ; 6(1): 159, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30591082

RESUMO

BACKGROUND: Microphthalmia Transcription Factor (MITF)family translocation renal cell carcinoma (tRCC) is a rare RCC subtype harboring TFE3/TFEB translocations. The prognosis in the metastatic (m) setting is poor. Programmed death ligand-1 expression was reported in 90% of cases, prompting us to analyze the benefit of immune checkpoint inhibitors (ICI) in this population. PATIENTS AND METHODS: This multicenter retrospective study identified patients with MITF family mtRCC who had received an ICI in any of 12 referral centers in France or the USA. Response rate according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. Genomic alterations associated with response were determined for 8 patients. RESULTS: Overall, 24 patients with metastatic disease who received an ICI as second or later line of treatment were identified. Nineteen (82.6%) of these patients had received a VEGFR inhibitor as first-line treatment, with a median PFS of 3 months (range, 1-22 months). The median PFS for patients during first ICI treatment was 2.5 months (range, 1-40 months); 4 patients experienced partial response (16,7%) and 3 (12,5%) had stable disease. Of the patients whose genomic alterations were analyzed, two patients with mutations in bromodomain-containing genes (PBRM1 and BRD8) had a clinical benefit. Resistant clones in a patient with exceptional response to ipilimumab showed loss of BRD8 mutations and increased mutational load driven by parallel evolution affecting 17 genes (median mutations per gene, 3), which were enriched mainly for O-glycan processing (29.4%, FDR = 9.7 × 10- 6). CONCLUSIONS: MITF family tRCC is an aggressive disease with similar responses to ICIs as clear-cell RCC. Mutations in bromodomain-containing genes might be associated with clinical benefit. The unexpected observation about parallel evolution of genes involved in O-glycosylation as a mechanism of resistance to ICI warrants exploration.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/genética , Imunomodulação/efeitos dos fármacos , Neoplasias Renais/genética , Fator de Transcrição Associado à Microftalmia/genética , Família Multigênica , Translocação Genética , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Criança , Pré-Escolar , Feminino , Genômica/métodos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Fator de Transcrição Associado à Microftalmia/antagonistas & inibidores , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
3.
J Infect ; 76(5): 483-488, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29432826

RESUMO

OBJECTIVES: Definitive diagnosis of invasive candidiasis (IC) may be difficult to achieve in patients with haematological malignancy (PHM). We aimed to evaluate the performance of BDG for the diagnosis and the follow-up of IC in PHM. PATIENTS AND METHODS: We retrospectively reviewed the serological data of BDG assay in adult and paediatric PHM, who developed candidemia or chronic disseminated candidiasis (CDC) through a 4-year period. Sensitivity and kinetics of BDG were determined for both clinical forms. RESULTS: In a panel of 3027 PHM, incidence rates of candidemia and CDC ranged between 0.74 and 0.77 and 0.30 and 0.44 according to the group of patients. At the time of diagnosis, 43.5% and 73% of cases of candidemia and CDC had a positive BDG assay, respectively. We found a significant correlation between the level of BDG at diagnosis and the outcome of candidemia (p = 0.022). In all cases of CDC, BDG negative results were obtained 2 to 6 months before recovery of the CT-scan lesions. CONCLUSIONS: BDG exhibits a low sensitivity to detect IC in PHM, but its kinetics correlates the clinical outcome. Additional studies are warranted in patients with CDC to evaluate the interest of monitoring BDG levels to anticipate the discontinuation of antifungal maintenance therapy.


Assuntos
Candidemia/diagnóstico , Candidíase Invasiva/diagnóstico , Candidíase/diagnóstico , Neoplasias Hematológicas/microbiologia , beta-Glucanas/sangue , Idoso , Anticorpos Antifúngicos , Antifúngicos/uso terapêutico , Candida , Candidemia/tratamento farmacológico , Candidíase/tratamento farmacológico , Candidíase Invasiva/tratamento farmacológico , Seguimentos , Humanos , Unidades de Terapia Intensiva , Cinética , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
4.
Arch Pediatr ; 24(4): 317-326, 2017 Apr.
Artigo em Francês | MEDLINE | ID: mdl-28242151

RESUMO

BACKGROUND: Considering the remarkable efficacy of the strategies for preventing mother-to-child transmission of HIV infection (PMTCT), failures are rare in high-resource countries and deserve further investigation. Moreover, infants have been found to be at increased risk of viral failure. We analyzed the factors related to the children's environment, including maternal psychological factors that may be associated with viral failure in children diagnosed before the age of 1 year. PATIENTS AND METHODS: Retrospective study of all HIV-infected infants, born in France between July 2003 and July 2013, diagnosed before the age of 1 year, cared for in a single reference center, comparing the group of children in viral success to the group of children presenting at least one episode of viral failure, using data available in their medical, psychological and social files. RESULTS: Out of 1061 infants included in the prospective PMTCT follow-up, eight infants were found HIV-positive and an additional six cases were referred from other centers before the age of 1 year, for a total of 14 children born to 13 mothers. Seven children presented durable optimal viral control (VL<50 c/mL) whereas seven others did not reach or maintain optimal viral control over time. The main difference between the two groups was the presence among the mothers of children with viral failure of severe psychological disorders, leading to treatment adherence problems in the mothers who were aware of their HIV status before pregnancy, and difficulties in giving their children's treatments correctly. CONCLUSIONS: Although seroconversion during pregnancy is responsible for a significant proportion of residual transmission in high-resource countries, severe psychological or psychiatric conditions in HIV-positive mothers play an important role on the risk of both MTC residual transmission and viral failure in their infants.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Feminino , Seguimentos , Infecções por HIV/psicologia , HIV-1/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Masculino , Adesão à Medicação/psicologia , Mães/psicologia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
6.
Bone Marrow Transplant ; 52(1): 80-87, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27595286

RESUMO

Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucémie de l'Enfant et de l'Adolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level ⩾350 ng/mL) was 42.2% (95%CI 37.2-47.2%). Factors significantly associated with IO were: 1) in univariate analysis: older age at transplant (P<0.001), allogeneic versus autologous transplantation (P<0.001), radiation-based preparative regimen (P=0.035) and recent period of transplantation (P<0.001); 2) in multivariate analysis: older age at transplant in quartiles (Odds Ratio (OR)=7.64, 95% CI: 3.73-15.64 for age >12.7 years and OR=5.36, 95% CI: 2.63-10.95 for age from 8.2 to 12.7 years compared to age < 4.7 years), acute myeloid leukemia (OR=3.23, 95% CI: 1.47-7.13), allogeneic graft (OR=4.34, 95% CI: 2.07-9.12 for alternative donors and OR=2.53, 95% CI: 1.2-5.33 for siblings, compared to autologous graft) and radiation-based conditioning regimen (OR=2.45, 95% CI: 1.09-5.53). Graft-versus-host disease was an additional risk factor for allogeneic graft recipients. In conclusion, IO is a frequent complication in pediatric long-term survivors after transplantation for acute leukemia, more frequently observed in older children, those transplanted from alternative donors or with graft-versus-host disease.


Assuntos
Sobreviventes de Câncer , Ferritinas/sangue , Transplante de Células-Tronco Hematopoéticas , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/epidemiologia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante , Fatores Etários , Aloenxertos , Criança , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/epidemiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Prevalência , Fatores de Risco , Doadores de Tecidos
7.
Bone Marrow Transplant ; 50(11): 1438-44, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26191949

RESUMO

We evaluated prospectively the incidence and risk factors of the metabolic syndrome (MS) and its components in 170 adult patients (mean age at evaluation: 24.8±5.4 years) who received an hematopoietic stem cell transplantation for childhood ALL, n=119, or AML, n=51. TBI was carried out in 124 cases; a busulfan-based conditioning was done in 30 patients. Twenty-nine patients developed a MS (17.1%, 95% confidence intervals: 11.7-23.6). The cumulative incidence was 13.4% at 25 years of age and 35.5% at 35 years of age. A higher body mass index (BMI) before transplantation and a growth hormone deficiency were associated with increased MS risk (P=0.002 and 0.01, respectively). MS risk was similar for patients who received TBI or busulfan-based conditioning. The TBI use increased the hyperglycemia risk (odds ratio (OR): 4.7, P=0.02). Women were at the risk of developing increased waist circumference (OR: 7.18, P=0.003) and low levels of high-density lipoprotein cholesterol (OR: 2.72, P=0.007). The steroid dose was not a risk factor. The MS occurs frequently among transplanted survivors of childhood leukemia. Its incidence increases with age. Both intrinsic (BMI, gender) and extrinsic factors (TBI, alkylating agents) contribute to its etiopathogenesis.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndrome Metabólica/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sobreviventes , Condicionamento Pré-Transplante/efeitos adversos , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Glicemia/análise , Índice de Massa Corporal , Bussulfano/uso terapêutico , HDL-Colesterol/sangue , Terapia Combinada , Feminino , Humanos , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Agonistas Mieloablativos/efeitos adversos , Agonistas Mieloablativos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Circunferência da Cintura , Irradiação Corporal Total/efeitos adversos , Adulto Jovem
9.
Arch Pediatr ; 20(1): 1-8, 2013 Jan.
Artigo em Francês | MEDLINE | ID: mdl-23266171

RESUMO

OBJECTIVES: To assess whether maternal HIV-positive status negatively affects family construction and the child's psychological environment. Could this be responsible for behavioral problems observed in children infected with or affected by HIV? MATERIAL AND METHODS: Interviews were conducted with 60 HIV+ mothers and their infants during the perinatal period, within 3 months of delivery, collected at the time of a pediatric outpatient visit within a PMTCT program. RESULTS: Half of the 60 mothers did not live with the infant's father, 56% of multiparous mothers were separated from their previous children. Sixty-five percent of the fathers were informed of the mother's HIV-positive status, although 90% of fathers who lived with the mothers were informed. During pregnancy, 80% of mothers reported psychological stress; after delivery, 72% of mothers suffered from not being allowed to breastfeed their infants, 43.5% expressed a fear of transmitting the infection to the child, and 40% avoided contacts with the infant. The impact of the mother's psychological stress and anxiety related to the risk of HIV transmission through breastfeeding and casual contacts were already noticeable in the first mother-child interrelations. CONCLUSIONS: Although the risk of MTC transmission in now very small, psychological troubles related to maternal HIV status may negatively affect the children's well-being and behavior, psychological support should be provided for mothers and children as part of comprehensive services.


Assuntos
Ansiedade , Aleitamento Materno/psicologia , Infecções por HIV/psicologia , Comportamento Materno/psicologia , Período Pós-Parto , Refugiados/psicologia , Estresse Psicológico , Adulto , África , Ansiedade/psicologia , Características da Família , Conflito Familiar/psicologia , Feminino , França/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Humanos , Lactente , Comportamento do Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Relações Mãe-Filho , Gravidez , Refugiados/estatística & dados numéricos , Fatores de Risco , Meio Social , Apoio Social , Inquéritos e Questionários
11.
Eur J Surg Oncol ; 35(1): 11-5, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17689043

RESUMO

EASL/AASLD guidelines clearly define indications for liver surgery for HCC: patients with single HCC and completely preserved liver function without portal hypertension. These guidelines exclude from operation many patients that could benefit from radical resection and that are daily scheduled for hepatectomy in surgical centers. Patients with large tumors or with portal vein thrombosis cannot be transplanted or treated by interstitial treatments. In selected cases liver resection may obtain good long-term outcomes, significantly better than non-curative therapies. In cases of multinodular HCC, liver transplantation is the treatment of choice within Milan criteria; patients beyond these limits can benefit from liver resection, especially if only two nodules are diagnosed: even if they have a worse prognosis, survival results after liver surgery are better than those reported after TACE or conservative treatments. EASL/AASLD guidelines excluded from operating patients with portal hypertension but data about this topic are not conclusive and further studies are necessary. Selected patients with mild portal hypertension could probably be scheduled for liver resection and, considering the shortage of donors, listing for transplantation could be avoided. In conclusion, guidelines for HCC treatment should consider good results of liver resection for advanced HCC, and indications for hepatectomy should be expanded in order not to exclude from radical therapy patients that could benefit from it.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Neoplasias Hepáticas/cirurgia , Guias de Prática Clínica como Assunto , Carcinoma Hepatocelular/complicações , Humanos , Neoplasias Hepáticas/complicações , Seleção de Pacientes
12.
Minerva Med ; 99(2): 219-22, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18431330

RESUMO

Sporadic descriptions of acute onset of watery diarrhea within a few hours to a few weeks azathioprine administration beginning have been reported, particularly in inflammatory bowel disease patients. This article reports the case of a woman treated with azathioprine because of type I autoimmune hepatitis, who developed acute watery diarrhea after more than two months of therapy. In two occasions the patient reassumed the drug and in a few hours diarrhea recurred. Subsequent 6-mercaptopurine treatment was well tolerated, suggesting that the previous side-effect could be due to the nitroimidazole moiety of azathioprine.


Assuntos
Azatioprina/efeitos adversos , Diarreia/induzido quimicamente , Imunossupressores/efeitos adversos , Doença Aguda , Idoso , Feminino , Hepatite Autoimune/tratamento farmacológico , Humanos
13.
Arch Pediatr ; 14(5): 461-6, 2007 May.
Artigo em Francês | MEDLINE | ID: mdl-17306514

RESUMO

OBJECTIVE: To study the feelings of HIV infected mothers during the perinatal period regarding circumstances of HIV diagnosis, disclosure to partner and fear of contamination. POPULATION AND METHODS: A study based upon personal interviews was carried out from November 2003 to January 2004 upon routine pediatric outpatient visits for infants born to HIV positive mothers. RESULTS: This study included 54 women of which 70% were from Sub-Saharan Africa. Fifty-nine per cent discovered their HIV status during a pregnancy. Seventy-seven per cent of partners were informed of maternal status. Among the women reluctant to inform their partner, the main reasons given were fear of violence and separation. Seventy-two per cent of interviewed women refused their spouses to be informed by the medical staff. Medical care during pregnancy (moral support, delivery) was judged as good by a majority of women (90%) who found the behavior of the staff mostly satisfactory. Final child serology remains the most definitive test for mothers, 47% of whom fear the risk of a potential postnatal contamination of their children. CONCLUSION: In these isolated women, many of whom have recently discovered their HIV status, a multidisciplinary approach including psychosocial support is essential.


Assuntos
Infecções por HIV/psicologia , Complicações Infecciosas na Gravidez/psicologia , África/etnologia , Estudos Transversais , Feminino , França , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Entrevistas como Assunto , Masculino , Satisfação do Paciente , Assistência Perinatal , Gravidez , Parceiros Sexuais , Revelação da Verdade
15.
Eur J Surg Oncol ; 33(1): 61-6, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17175128

RESUMO

AIM: To evaluate the impact of postoperative injection into the hepatic artery of 131-iodine-labeled lipiodol on disease-free and overall survival rates in patients who underwent liver surgical resection for hepatocellular carcinoma. METHODS: Ten consecutive patients with HCV (hepatitis C virus)-related cirrhosis who underwent liver surgical resection for hepatocellular carcinoma were treated with adjuvant injection of 131-iodine-labeled lipiodol. They were matched with 20 HCV-positive cirrhotic controls who underwent liver resection alone; patients were paired in terms of age, Child-Pugh class, tumor size, microscopic vascular invasion, tumor histological pattern, presence of satellite nodules and type of surgical resection. Recurrence was defined as the development of a new hypervascularizated nodule in the liver. RESULTS: No significant differences were found between the two groups in clinical, biologic and histologic characteristics, except a lower platelet count in the control group. None of the treated patients developed an intrahepatic recurrence until the 15th month from liver resection, whereas recurrences occurred in nine of the 20 patients in the control group (p=0.01). From 18 months onwards, recurrences appeared also in the treated patients, and after 36 months of follow-up both recurrence rate and overall survival were not significantly different between the two groups. CONCLUSIONS: Intrahepatic injection of 131-iodine-labeled lipiodol improves the disease-free survival rate following liver resection of hepatocellular carcinoma in the short term up to 15 months; this advantage fades, however, away after 36 months.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Hepatite C Crônica/complicações , Óleo Iodado/uso terapêutico , Cirrose Hepática/etiologia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Seguimentos , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/análise , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Incidência , Radioisótopos do Iodo , Itália/epidemiologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
16.
Leukemia ; 21(2): 238-47, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17170721

RESUMO

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Encefalopatias Metabólicas/induzido quimicamente , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Fatores Etários , Encefalopatias Metabólicas/epidemiologia , Encefalopatias Metabólicas/prevenção & controle , Criança , Pré-Escolar , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Neurotoxinas , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Medição de Risco
18.
Aliment Pharmacol Ther ; 24(7): 1079-86, 2006 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-16984502

RESUMO

BACKGROUND: There is yet no established treatment for chronic hepatitis C patients non-responder to standard interferon and ribavirin. AIM: To evaluate efficacy and safety of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in such patients. METHODS: 161 non-responders to standard interferon and ribavirin were randomized into two groups: 81 patients (Group 1) were given weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily for 12 months, 80 patients (Group 2) received weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily and amantadine 200 mg/daily for 12 months. RESULTS: At the end of follow-up, HCV-RNA was negative in 29.6% of Group 1 and in 21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded better to bi-therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among patients with genotypes 2 and 3 there was a trend towards a higher sustained virological response rate when retreated with triple treatment (80% vs. 75%, P = 0.82). On multivariate analysis, genotype 1 or 4, high body mass index and >20% reduction of Peg-interferon were associated with the treatment failure. CONCLUSIONS: The addition of amantadine does not improve the overall SVR rate in non-responder patients retreated with Peg-IFN and ribavirin; however, about 30% of non-responders may achieve a sustained response, in particular patients with genotypes 2 and 3 show a high SVR (75%).


Assuntos
Amantadina/uso terapêutico , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Quimioterapia Combinada , Seguimentos , Humanos , Interferon alfa-2 , Pessoa de Meia-Idade , Proteínas Recombinantes , Resultado do Tratamento
20.
Minerva Gastroenterol Dietol ; 52(1): 47-52, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16554706

RESUMO

Mortality due to hepatocellular carcinoma (HCC) is still high, because of its development in liver with impaired function due to underlying cirrhosis, of its chemoresistance and of its high rate of recurrence. Liver transplantation is considered the most efficacious treatment for patients with HCC. However, the low availability of organs limits the offer of this option to all candidates. Furthermore, liver transplantation is not lacking in risk of tumour recurrence. Other curative options include surgical resection and ablation using percutaneous techniques. Such approaches give similar and satisfactory survival rates, providing that patient selection is optimal in terms of tumour size and liver function. Since even in the presence of a radical therapeutic result this cancer maintains a high tendency for local recurrence, it is very important to explore the adjuvant ways to increase the disease-free survival in patients surgically treated. Treatment with interferon a and intrahepatic injection of (131)-Iodine labelled lipiodol ((131)I-Lipiodol) are instead showing encouraging results. This review presents a concise update on this issue.


Assuntos
Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Antivirais/uso terapêutico , Humanos , Interferon-alfa/uso terapêutico
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