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1.
Monatsschr Kinderheilkd ; 169(5): 443-450, 2021.
Artigo em Alemão | MEDLINE | ID: mdl-33746294

RESUMO

Febrile neutropenia is the most common potential emergency situation in children and adolescents with cancer. The host response of these patients is severely compromised by treatment-induced immunosuppression resulting in a lack of important defence mechanisms, so that bacterial infections and in certain risk groups also fungal infections can be life threatening. As the clinical course of these infectious complications may be rapid and fatal, early antibiotic treatment can save lives. This article aims to raise awareness to this emergency situation and gives an overview of the management of pediatric cancer patients with febrile neutropenia.

2.
Clin Microbiol Infect ; 25(9): 1096-1113, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158517

RESUMO

SCOPE: Presenting symptoms, distributions and patterns of diseases and vulnerability to invasive aspergillosis (IA) are similar between children and adults. However, differences exist in the epidemiology and underlying conditions, the usefulness of newer diagnostic tools, the pharmacology of antifungal agents and in the evidence from interventional phase 3 clinical trials. Therefore, the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) have developed a paediatric-specific guideline for the diagnosis and management of IA in neonates and children. METHODS: Review and discussion of the scientific literature and grading of the available quality of evidence was performed by the paediatric subgroup of the ESCMID-ECMM-European Respiratory Society (ERS) Aspergillus disease guideline working group, which was assigned the mandate for the development of neonatal- and paediatric-specific recommendations. QUESTIONS: Questions addressed by the guideline included the epidemiology of IA in neonates and children; which paediatric patients may benefit from antifungal prophylaxis; how to diagnose IA in neonates and children; which antifungal agents are available for use in neonates and children; which antifungal agents are suitable for prophylaxis and treatment of IA in neonates and children; what is the role of therapeutic drug monitoring of azole antifungals; and which management strategies are suitable to be used in paediatric patients. This guideline provides recommendations for the diagnosis, prevention and treatment of IA in the paediatric population, including neonates. The aim of this guideline is to facilitate optimal management of neonates and children at risk for or diagnosed with IA.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/normas , Aspergillus/efeitos dos fármacos , Criança , Gerenciamento Clínico , Monitoramento de Medicamentos , Humanos , Recém-Nascido
3.
Clin Microbiol Infect ; 24 Suppl 1: e1-e38, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29544767

RESUMO

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus/isolamento & purificação , Gerenciamento Clínico , Anticorpos Antifúngicos/sangue , Antifúngicos/farmacologia , Aspergilose/complicações , Aspergilose/imunologia , Aspergillus/efeitos dos fármacos , Aspergillus/imunologia , Biópsia/métodos , Lavagem Broncoalveolar , Diagnóstico Precoce , Flucitosina/farmacologia , Flucitosina/uso terapêutico , Galactose/análogos & derivados , Humanos , Hospedeiro Imunocomprometido , Testes Imunológicos , Aspergilose Pulmonar Invasiva/diagnóstico , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Imageamento por Ressonância Magnética , Mananas/análise , Testes de Sensibilidade Microbiana , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Tomografia Computadorizada por Raios X , Triazóis/farmacologia , Triazóis/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêutico
4.
Leukemia ; 31(12): 2807-2814, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28443606

RESUMO

We conducted a cytogenetic analysis of 642 children with de novo acute myeloid leukemia (AML) treated on the AML-Berlin-Frankfurt-Münster (BFM) 04 protocol to determine the prognostic value of specific chromosomal aberrations including monosomal (MK+), complex (CK+) and hypodiploid (HK+) karyotypes, individually and in combination. Multivariate regression analysis identified in particular MK+ (n=22) as a new independent risk factor for poor event-free survival (EFS 23±9% vs 53±2% for all other patients, P=0.0003), even after exclusion of four patients with monosomy 7 (EFS 28±11%, P=0.0081). CK+ patients without MK had a better prognosis (n=47, EFS 47±8%, P=0.46) than those with MK+ (n=12, EFS 25±13%, P=0.024). HK+ (n=37, EFS 44±8% for total cohort, P=0.3) influenced outcome only when t(8;21) patients were excluded (remaining n=16, EFS 9±8%, P<0.0001). An extremely poor outcome was observed for MK+/HK+ patients (n=10, EFS 10±10%, P<0.0001). Finally, isolated trisomy 8 was also associated with low EFS (n=16, EFS 25±11%, P=0.0091). In conclusion, monosomal karyotype is a strong and independent predictor for high-risk pediatric AML. In addition, isolated trisomy 8 and hypodiploidy without t(8;21) coincide with dismal outcome. These results have important implications for risk stratification and should be further validated in independent pediatric cohorts.


Assuntos
Variação Genética , Genótipo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Aberrações Cromossômicas , Cromossomos Humanos Par 7 , Ensaios Clínicos como Assunto , Feminino , Humanos , Cariótipo , Leucemia Mieloide Aguda/diagnóstico , Masculino , Monossomia , Mutação , Prognóstico , Análise de Sobrevida
5.
Klin Padiatr ; 228(6-07): 294-306, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27846659

RESUMO

Rare histiocytoses, also called non-Langerhans cell histiocytoses, include all proliferative disorders of histiocytes, macrophages and dendritic cells that are not classified as Langerhans cell histiocytosis (LCH) and do not belong to the hemophagocytic lymphohistiocytosis (HLH) group of diseases. Thus, the term includes numerous benign or malignant, localized or systemic, adult or pediatric diseases. The classification of the histiocytic disorders has been revised several times. Here, we follow the classification recently published by Jean Francois Emile and an international expert panel, defining subgroups of histiocytoses described as L-Group, C-Group, M-Group, R-Group, and H-Group, which stands for LCH-like, cutaneous or mucocutaneous, malignant, Rosai-Dorfman-Disease like and HLH like. Some of the diseases have an excellent prognosis after resection or even disappear spontanously, others progress rapidly, requiring intensive systemic therapies. The malignant non-Langerhans cell histiocytoses in general have a poor prognosis, here, complex chemotherapy protocols are usually applied, with inconsistant results. An interesting perspective in non-malignant rare histiocytoses might be small molecular inhibitors, in particular BRAF inhibitors, since BRAF mutations have been found in some subtypes of non-Langerhans cell histiocytoses. By prospective and retrospective collection of experiences in a new registry (the "International Rare Histiocytic Disorders Registry", IRHDR), knowledge about these rare diseases might hopefully be improved.


Assuntos
Histiocitose de Células não Langerhans/diagnóstico , Histiocitose de Células não Langerhans/terapia , Ensaios Clínicos como Assunto , Diagnóstico Diferencial , Histiocitose de Células não Langerhans/classificação , Humanos , Prognóstico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Resultado do Tratamento
6.
Blood Cancer J ; 6: e382, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26771808

RESUMO

Infections are an important cause for morbidity and mortality in pediatric acute myeloid leukemia (AML). We therefore characterized infectious complications in children treated according to the trial AML-BFM 2004. Patients with Down syndrome were excluded from the analysis. Data were gathered from the medical records in the hospital where the patients were treated. A total of 405 patients (203 girls; median age 8.4 years) experienced 1326 infections. Fever without identifiable source occurred in 56.1% of the patients and clinically and microbiologically documented infections in 17.5% and 32.4% of the patients, respectively. In all, 240 Gram-positive (112 viridans group streptococci) and 90 Gram-negative isolates were recovered from the bloodstream. Invasive fungal infection was diagnosed in 3% of the patients. Three children each died of Gram-negative bacteremia and invasive aspergillosis, respectively. As compared with the results of AML-BFM 93 with lower dose intensity, infection-related morbidity was slightly higher in AML-BFM 2004 (3.3. versus 2.8 infections per patient), whereas infection-related mortality significantly decreased (1.5% versus 5.4%; P=0.003). Specific anti-infective recommendations included in the treatment protocol, regular training courses for pediatric hematologists and increasing experience may be the reason for reduced infection-related mortality in children with AML. Further studies are needed to decrease infection-related morbidity.


Assuntos
Infecções/etiologia , Infecções/mortalidade , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/mortalidade , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Sepse/etiologia , Sepse/mortalidade
7.
Mycoses ; 58(12): 735-45, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26497302

RESUMO

The increasing incidence of invasive fungal diseases (IFD), most of all invasive aspergillosis (IA) in immunocompromised patients emphasises the need to improve the diagnostic tools for detection of fungal pathogens. We investigated the diagnostic performance of a multifungal DNA-microarray detecting 15 different fungi [Aspergillus, Candida, Fusarium, Mucor, Rhizopus, Scedosporium and Trichosporon species (spp.)] in addition to an Aspergillus specific polymerase chain reaction (PCR) assay. Biopsies, bronchoalveolar lavage and peripheral blood samples of 133 immunocompromised patients (pts) were investigated by a multifungal DNA-microarray as well as a nested Aspergillus specific PCR assay. Patients had proven (n = 18), probable (n = 29), possible (n = 48) and no IFD (n = 38) and were mostly under antifungal therapy at the time of sampling. The results were compared to culture, histopathology, imaging and serology, respectively. For the non-Aspergillus IFD the microarray analysis yielded in all samples a sensitivity of 64% and a specificity of 80%. Best results for the detection of all IFD were achieved by combining DNA-microarray and Aspergillus specific PCR in biopsy samples (sensitivity 79%; specificity 71%). The molecular assays in combination identify genomic DNA of fungal pathogens and may improve identification of causative pathogens of IFD and help overcoming the diagnostic uncertainty of culture and/or histopathology findings, even during antifungal therapy.


Assuntos
Aspergilose/diagnóstico , Aspergillus fumigatus/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adulto , Antifúngicos/uso terapêutico , Aspergilose/sangue , Aspergilose/diagnóstico por imagem , Aspergillus fumigatus/genética , Aspergillus fumigatus/imunologia , Sequência de Bases , Biópsia por Agulha , Lavagem Broncoalveolar , DNA Fúngico/isolamento & purificação , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Dados de Sequência Molecular , Radiografia , Sensibilidade e Especificidade
8.
Klin Padiatr ; 227(3): 116-22, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25985446

RESUMO

BACKGROUND: The outcome in children and adolescents with high-risk (HR) acute myeloid leukemia (AML) is still unsatisfactory. Therefore, in study AML-BFM 2004 we aimed to improve outcome of HR-patients by adding moderately dosed 2-Chloro-2-Deoxyadenosine (2-CDA) to the respective consolidation treatment backbone without increasing toxicity. The aim was to improve prognosis especially in FAB M4/M5/MLL patients, who represent the largest subgroup of HR patients. PATIENTS AND METHODS: In total, 343 children and adolescents with HR-AML were randomized to receive or not 2-CDA (6 mg/m²/d, days 1, 3) in combination with cytarabine/idarubicine (AI=500 mg/m² cytarabine 5 days continuous infusion plus 7 mg/m²/d idarubicin, days 3 and 5). RESULTS: RESULTS for patients of the AI/2-CDA arm (n=168) vs. the AI-arm (n=175) were similar: 5-year overall survival 68±4 vs. 72±4%, plogrank=0.38, event-free survival 53±4 vs. 49±4%, plogrank=0.77; cumulative incidence of relapse at 5 years: 35±4 vs. 37±4%, p(Gray)=0.89. RESULTS in patients with MLL rearrangement or FAB M4/M5 were also similar in the treatment groups. In addition, toxicities did not differ between the two arms. CONCLUSION: We conclude that additional, moderate dose 2-CDA does not improve prognosis in HR-patients when given during consolidation treatment. Its effect might be too low in this multidrug regimen, where the strongest effects are achieved during induction, or the chosen dose of 2-CDA might have been too low.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/administração & dosagem , Cladribina/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Idarubicina/administração & dosagem , Idarubicina/efeitos adversos , Infusões Intravenosas , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Prognóstico , Taxa de Sobrevida
10.
J Antimicrob Chemother ; 70(5): 1527-30, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25564562

RESUMO

BACKGROUND: Current guidelines recommend antifungal prophylaxis for children at high risk for invasive fungal disease (IFD), but the use of polyenes and triazoles may not be feasible in some patients due to toxicities and drug-drug interactions. Micafungin is well tolerated, with intravenous daily dosing being the current standard. Recent reports indicate safety and efficacy of intermittent dosing of micafungin. METHODS: We analysed safety, efficacy and micafungin serum concentrations of children at high risk for IFD receiving prophylactic micafungin between 3 and 4 mg/kg twice weekly. All children were intolerant or had contraindications to polyenes and triazoles. RESULTS: A total of 21 children (median age = 9 years) at high risk for IFD were included in the analysis. No significant clinical adverse event occurred, and end of treatment values of parameters of renal and hepatic function in serum were not different from baseline. Proven or probable breakthrough IFD did not occur in any of the patients. In 9 out of 11 patients in whom plasma micafungin concentrations were assessed, the first trough concentration exceeded 150 ng/mL, a concentration proposed to be effective for prophylaxis. CONCLUSIONS: Our data indicate that micafungin administered twice weekly at a dosage of 3-4 mg/kg of bodyweight could be a convenient, safe and efficient alternative for antifungal prophylaxis in children at high risk for IFD.


Assuntos
Antifúngicos/administração & dosagem , Quimioprevenção/métodos , Equinocandinas/administração & dosagem , Fungemia/prevenção & controle , Lipopeptídeos/administração & dosagem , Adolescente , Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Criança , Pré-Escolar , Equinocandinas/efeitos adversos , Equinocandinas/farmacocinética , Feminino , Humanos , Lactente , Testes de Função Renal , Lipopeptídeos/efeitos adversos , Lipopeptídeos/farmacocinética , Testes de Função Hepática , Masculino , Micafungina , Resultado do Tratamento
11.
Leukemia ; 28(10): 1941-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24762460

RESUMO

Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I antigens under resting conditions. These characteristics have made MSC an appealing candidate for cell therapy after hematopoietic stem cell transplantation (HSCT), for example, for treatment of graft-versus-host disease (GvHD) or for graft rejection prevention/treatment in allogeneic HSCT recipients. Unfortunately, information regarding the effect of MSC infusion on the host response to infectious agents is scarce, and study results on infectious complications in patients receiving MSC are conflicting. The present review focuses on the available data from in vitro studies and animal models regarding the interaction of MSC with bacterial, viral and fungal pathogens. In a clinical part, we present the current information on infectious complications in allogeneic HSCT recipients who had received MSCs as prophylaxis or treatment of GvHD disease.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Mesenquimais/citologia , Animais , Anti-Infecciosos/farmacologia , Infecções Bacterianas/complicações , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Antígenos HLA/metabolismo , Humanos , Imunossupressores/farmacologia , Micoses/complicações , Esteroides/farmacologia , Viroses/complicações
12.
J Clin Microbiol ; 51(12): 4178-85, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24108612

RESUMO

Although it is a severe complication in immunocompromised patients, diagnosing invasive fungal disease (IFD), especially invasive aspergillosis (IA), remains difficult. In certain clinical scenarios, examining tissue samples for identification of the infectious organism becomes important. As culture-based methods rarely yield results, the performance of an Aspergillus-specific nested PCR in fresh tissue or pleural effusion samples was evaluated. Fresh tissue (n = 59) and effusion (n = 47) specimens from 79 immunocompromised patients were subjected to an Aspergillus-specific PCR assay. Twenty-six patients had proven (n = 20) or probable (n = 6) IFD, according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, while the remaining patients were classified as having either possible IFD (n = 30) or no IFD (n = 23). IA was identified as the underlying IFD in 21/26 proven/probable cases. PCR positivity was observed for 18/21 proven/probable and 6 possible IA cases; cases classified as no IA did not show positive signals. Patients with proven IFD (n = 5) with cultures positive for non-Aspergillus molds also had negative Aspergillus PCR results. Aspergillus PCR performance analysis yielded sensitivity and specificity values of 86% (95% confidence interval [CI], 65% to 95%) and 100% (95% CI, 86% to 100%), respectively, thus leading to a diagnostic odds ratio of >200. In this analysis, good diagnostic performance of the PCR assay for detection of IA was observed for tissue samples, while effusion samples showed lower sensitivity rates. PCR testing represents a complementary tool; a positive PCR result strengthens the likelihood of IA, whereas IA seems unlikely in cases with negative results but findings could indicate non-Aspergillus IFD. Thus, PCR testing of these specimens enhances the diagnostic capabilities.


Assuntos
Aspergilose/diagnóstico , Aspergillus/isolamento & purificação , Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspergillus/genética , Criança , Pré-Escolar , Feminino , Humanos , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural/microbiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
13.
Transpl Infect Dis ; 15(4): 430-4, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23647945

RESUMO

Despite the availability of new antifungal compounds, invasive fungal disease is associated with a high mortality in hematopoietic stem cell transplant (HSCT) recipients. A growing body of evidence suggests that T lymphocytes from the T-helper type 1 (TH 1) play an important role in the antifungal host defense, and preliminary data indicate a potential benefit of infusing donor-derived antifungal TH 1 cells to HSCT patients suffering from invasive fungal disease. Unfortunately, it is unclear to date whether the function of these cells is affected by concomitantly administered antifungal agents. We therefore analyzed the effects of various concentrations of commonly used antifungal compounds such as amphotericin B, caspofungin, fluconazole, voriconazole, and posaconazole on the functional properties of cultivated human antifungal TH 1 cells. None of the antifungal compounds tested significantly influenced the secretion of interferon-γ and tumor necrosis factor-α, and only posaconazole at high concentrations slightly decreased proliferation of antifungal TH 1 cells. Our data indicate that the antifungal agents tested do not significantly affect the functional properties of antifungal TH 1 cells and can therefore be concomitantly administered.


Assuntos
Antifúngicos/farmacologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Antifúngicos/uso terapêutico , Células Cultivadas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Interferon gama/efeitos dos fármacos , Interferon gama/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Micoses/imunologia , Micoses/prevenção & controle , Células Th1/metabolismo , Triazóis/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
14.
Klin Padiatr ; 224(6): 404-15, 2012 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-23143768

RESUMO

BACKGROUND: Currently, management of antibody deficient patients differs significantly among caregivers. Evidence and consensus based (S3) guidelines for the treatment of primary antibody deficiencies were developed to improve the management of these patients. METHODS: Based on a thorough analysis of current evidence (systematic literature search in PubMed; deadline November 2011) 14 recommendations were finalized during a consensus meeting in Frankfurt in November 2011 using structured consensus methods (nominal group technique). Experts were nominated by their scientific societies/patient initiatives (Tab. 1). RESULTS: The guidelines focus on indication, practical issues and monitoring of immunoglobulin replacement therapy as well as on different routes of administration. Furthermore recommendations regarding supportive measures such as antiinfective therapy, vaccinations and physiotherapy are given. Combining literature evidence and experience of caregivers within this evidence and consensus based guidelines offers the chance to improve the quality of care for anti-body deficient patients.


Assuntos
Comportamento Cooperativo , Síndromes de Imunodeficiência/terapia , Comunicação Interdisciplinar , Adulto , Anti-Infecciosos/uso terapêutico , Pré-Escolar , Terapia Combinada , Medicina Baseada em Evidências , Humanos , Imunização Passiva , Modalidades de Fisioterapia , Melhoria de Qualidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinação
15.
Klin Padiatr ; 224(6): 377-81, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23047832

RESUMO

BACKGROUND: In adult cancer patients the negative predictive value of elevated CRP levels has been described for several malignancies. Only few studies have analyzed the prognostic role of CRP in children and adolescents with classical HL. In these studies elevated CRP levels correlate with the presence of classical risk factors and adverse outcome. PATIENTS AND METHODS: The prognostic role of CRP for patients with classical HL admitted to the GPOH-HD-2002 study was analyzed retrospectively. RESULTS: CRP levels were documented for 369 of 573 patients. Significant (p<0.05) increased median CRP levels were found in the presence of B-Symptoms (25.7 vs. 5.1 mg/l), extranodal involvement (21.5 vs. 7.5 mg/l), elevated erythrocyte sedimentation rate (ESR, 13.0 vs. 1.0 mg/l) and stage III/IV disease (15.5 vs. 5.3 mg/l). 83.9% of patients with elevated and 45.8% of patients with normal CRP had an ESR >30 mm/h. CONCLUSION: Elevated CRP levels were associated with classical risk factors of HL. CRP and ESR may reflect different biological processes. CRP was prognostic within early stage TG-1 patients treated with reduced treatment, but not within advanced stage TG-2+3.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Doença de Hodgkin/sangue , Doença de Hodgkin/diagnóstico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sedimentação Sanguínea , Criança , Estudos de Coortes , Esquema de Medicação , Feminino , Seguimentos , Alemanha , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
16.
Br J Cancer ; 106(10): 1626-37, 2012 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-22568999

RESUMO

BACKGROUND: Objectives were to compare systemic mould-active vs fluconazole prophylaxis in cancer patients receiving chemotherapy or haematopoietic stem cell transplantation (HSCT). METHODS: We searched OVID MEDLINE and the Cochrane Central Register of Controlled Trials (1948-August 2011) and EMBASE (1980-August 2011). Randomised controlled trials of mould-active vs fluconazole prophylaxis in cancer or HSCT patients were included. Primary outcome was proven/probable invasive fungal infections (IFI). Analysis was completed by computing relative risks (RRs) using a random-effects model and Mantel-Haenszel method. RESULTS: From 984 reviewed articles, 20 were included in this review. Mould-active compared with fluconazole prophylaxis significantly reduced the number of proven/probable IFI (RR 0.71, 95% CI 0.52 to 0.98; P=0.03). Mould-active prophylaxis also decreased the risk of invasive aspergillosis (IA; RR 0.53, 95% confidence interval (CI) 0.37-0.75; P=0.0004) and IFI-related mortality (RR 0.67, 95% CI 0.47-0.96; P=0.03) but is also associated with an increased risk of adverse events (AEs) leading to antifungal discontinuation (RR 1.95, 95% CI 1.24-3.07; P=0.004). There was no decrease in overall mortality (RR 1.0; 95% CI 0.88-1.13; P=0.96). CONCLUSION: Mould-active compared with fluconazole prophylaxis significantly reduces proven/probable IFI, IA, and IFI-related mortality in cancer patients receiving chemotherapy or HSCT, but increases AE and does not affect overall mortality. (PROSPERO Registration: CRD420111174).


Assuntos
Antifúngicos/uso terapêutico , Antineoplásicos/efeitos adversos , Fluconazol/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Micoses/prevenção & controle , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade
17.
Support Care Cancer ; 20(6): 1135-45, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22402749

RESUMO

BACKGROUND: There is no consensus on whether therapeutic intensity can be reduced safely in children with low-risk febrile neutropenia (FN). Our primary objective was to determine whether there is a difference in efficacy between outpatient and inpatient management of children with low-risk FN. Our secondary objective was to compare oral and parenteral antibiotic therapy in this population. METHODS: We performed electronic searches of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials, and limited studies to prospective pediatric trials in low-risk FN. Percentages were used as the effect measure. RESULTS: From 7,281 reviewed articles, 16 were included in the meta-analysis. Treatment failure, including antibiotic modification, was less likely to occur in the outpatient setting compared with the inpatient setting (15 % versus 28 %, P = 0.04) but was not significantly different between oral and parenteral antibiotic regimens (20 % versus 22 %, P = 0.68). Of the 953 episodes treated in the outpatient setting and 676 episodes treated with oral antibiotics, none were associated with infection-related mortality. CONCLUSION: Based on the combination of results from all prospective studies to date, outpatient and oral antibiotic management of low-risk FN are effective in children and should be incorporated into clinical care where feasible.


Assuntos
Antibacterianos/administração & dosagem , Febre/tratamento farmacológico , Neutropenia/tratamento farmacológico , Administração Oral , Assistência Ambulatorial , Criança , Febre/etiologia , Humanos , Neoplasias/tratamento farmacológico , Neutropenia/etiologia , Fatores de Risco , Falha de Tratamento , Resultado do Tratamento
18.
Klin Padiatr ; 224(3): 139-42, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22377741

RESUMO

Autologous stem cell transplantation (SCT) has become standard therapy in high risk stage IV neuroblastoma (NB) patients. Residual NB cells in the bone marrow (BM) shortly before SCT may shape the overall survival.Thus, we sought to thoroughly investigate minimal residual disease (MRD) in BM prior to SCT using conventional and real time RT-PCR for tyrosine hydroxylase (TH) as well as morphology. To avoid influence of residual NB cells in the stem cell harvest, 17 patients transplanted with MRD negative grafts (n=11 CD34-selected and n=6 unmanipulated) are included in the final analysis, only.35% of these patients are alive with a median follow up of 8.6 years. In the BM of 9/17 patients residual NB cells could be detected < 40 d before SCT. These patients had a significant lower overall survival compared to patients without BM involvement based on combined RT-PCR and morphology results (11% vs. 62%, p=0.026) or using RT-PCR, only (p=0.01). In contrast morphology on its own did not lead to a significant discrimination between both groups.Our results obtained in a small cohort of stage IV NB patients suggest that MRD diagnostic in the BM shortly before SCT might be a valuable predictive tool for these patients but requires conformation in a multicenter study.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neuroblastoma/cirurgia , Adolescente , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Medula Óssea/patologia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Reação em Cadeia da Polimerase , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Tirosina 3-Mono-Oxigenase/análise , Adulto Jovem
19.
Leukemia ; 26(4): 654-61, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21968880

RESUMO

Infants <1 year of age have a high prevalence of prognostically unfavorable leukemias and a presumed susceptibility to treatment-related toxicities. A total of 125 infants with acute myeloid leukemia (AML) were treated in studies AML-BFM-98 (n = 59) and -2004 (n = 66). Treatment regimens of both studies were comparable, consisting of intensive induction followed by four courses (mainly high-dose cytarabine and anthracyclines). Allogeneic-hematopoietic stem-cell-transplantation (allo-HSCT) in 1st remission was optional for high-risk (HR) patients. Most infants (120/125=96%) were HR patients according to morphological, cytogenetic/molecular genetic and response criteria. Five-year overall survival was 66 ± 4%, and improved from 61 ± 6% in study-98 to 75 ± 6% in study-2004 (P(logrank) 0.14) and event-free survival rates were 44 ± 6% and 51 ± 6% (P(logrank) 0.66), respectively. Results in HR infants were similar to those of older HR children (1-<2- or 2-<10-year olds, P(logrank) 0.90 for survival). Survival rates of HSCT in 1st remission, initial partial response and after relapse were high (13/14, 2/8 and 20/30 patients, respectively). The latter contributes to excellent 5-year survival after relapse (50±8%). Despite more severe infections and pulmonary toxicities in infants, treatment-related death rate was identical to that of older children (3%). Our data indicate that intensive frontline and relapse AML treatment is feasible in infants, toxicities are manageable, and outcome is favorable.


Assuntos
Leucemia Mieloide Aguda/terapia , Antraciclinas/administração & dosagem , Criança , Pré-Escolar , Citarabina/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Análise Multivariada , Proteína de Leucina Linfoide-Mieloide/genética , Terapia de Salvação , Resultado do Tratamento
20.
Eur J Clin Microbiol Infect Dis ; 31(7): 1435-42, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22048844

RESUMO

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.


Assuntos
Acetamidas/uso terapêutico , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Oxazolidinonas/uso terapêutico , Adolescente , Áustria , Criança , Pré-Escolar , Feminino , Alemanha , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Linezolida , Masculino , Uso Off-Label/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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