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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.
Eur J Pediatr ; 174(5): 675-86, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25804192

RESUMO

UNLABELLED: In a prospective multicentre study of bloodstream infection (BSI) from November 01, 2007 to July 31, 2010, seven paediatric cancer centres (PCC) from Germany and one from Switzerland included 770 paediatric cancer patients (58% males; median age 8.3 years, interquartile range (IQR) 3.8-14.8 years) comprising 153,193 individual days of surveillance (in- and outpatient days during intensive treatment). Broviac catheters were used in 63% of all patients and Ports in 20%. One hundred forty-two patients (18%; 95% CI 16 to 21%) experienced at least one BSI (179 BSIs in total; bacteraemia 70%, bacterial sepsis 27%, candidaemia 2%). In 57%, the BSI occurred in inpatients, in 79% after conventional chemotherapy. Only 56 % of the patients showed neutropenia at BSI onset. Eventually, patients with acute lymphoblastic leukaemia (ALL) or acute myeloblastic leukaemia (AML), relapsed malignancy and patients with a Broviac faced an increased risk of BSI in the multivariate analysis. Relapsed malignancy (16%) was an independent risk factor for all BSI and for Gram-positive BSI. CONCLUSION: This study confirms relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. On a unit level, data on BSIs in this high-risk population derived from prospective surveillance are not only mandatory to decide on empiric antimicrobial treatment but also beneficial in planning and evaluating preventive bundles. WHAT IS KNOWN: • Paediatric cancer patients face an increased risk of nosocomial bloodstream infections (BSIs). • In most cases, these BSIs are associated with the use of a long-term central venous catheter (Broviac, Port), severe and prolonged immunosuppression (e.g. neutropenia) and other chemotherapy-induced alterations of host defence mechanisms (e.g. mucositis). What is New: • This study is the first multicentre study confirming relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. • It describes the epidemiology of nosocomial BSI in paediatric cancer patients mainly outside the stem cell transplantation setting during conventional intensive therapy and argues for prospective surveillance programmes to target and evaluate preventive bundle interventions.


Assuntos
Bacteriemia/epidemiologia , Candidemia/epidemiologia , Infecção Hospitalar/epidemiologia , Leucemia Mieloide Aguda/epidemiologia , Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Bacteriemia/microbiologia , Patógenos Transmitidos pelo Sangue , Institutos de Câncer/estatística & dados numéricos , Candidemia/microbiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Criança , Infecção Hospitalar/microbiologia , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/microbiologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologia , Estudos Prospectivos , Fatores de Risco
4.
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
5.
Clin Exp Immunol ; 173(2): 372-80, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23607573

RESUMO

In 2009, a federally funded clinical and research consortium (PID-NET, http://www.pid-net.org) established the first national registry for primary immunodeficiencies (PID) in Germany. The registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID.


Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Sistema de Registros , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Alemanha , Humanos , Síndromes de Imunodeficiência/genética , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
6.
Transpl Infect Dis ; 14(6): 589-94, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23013490

RESUMO

BACKGROUND: For children with hemato-oncologic diseases, especially after hematopoietic stem cell transplantation (HSCT), the risk for developing complications related to pandemic influenza A (H1N1) 2009 (pH1N1) infection is largely unknown. METHODS: A retrospective chart study was performed of pH1N1 cases diagnosed between October 2009 to January 2010 in the hemato-oncologic unit of the University Children's Hospital of Düsseldorf, Germany. FINDINGS: In total, 21 children were diagnosed with laboratory-confirmed pH1N1; in 16 patients with malignancies (acute leukemia 7, lymphoma 4, solid tumors 2, others 3) and in 5 with benign hematologic disorders. Five patients had undergone prior HSCT, although 1 patient was diagnosed during conditioning therapy with high-dose chemotherapy in preparation for haploidentical HSCT. Most frequent symptoms were fever (>38.5°C) and cough (in 100%), and rhinorrhea (57%). The 2 patients acquiring pH1N1 infection under high-dose or intensive chemotherapy did not require intensive care or mechanical ventilation, and both recovered under antiviral therapy. Oseltamivir was administered to 11 patients; in 1 patient, therapy was switched, on a compassionate-use basis, to intravenous zanamivir because of lack of clinical improvement after oseltamivir therapy. Complications were hospitalization (19%), demand of oxygen supplementation, delay/interruption of antineoplastic therapy, and prolonged administration of antibiotics and antipyretics. CONCLUSION: In the investigated patient population, pH1N1 was mild in most cases, but was associated with substantial morbidity in a proportion of patients and led to interruption and delay in anticancer treatment.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/virologia , Neoplasias/complicações , Pandemias , Adolescente , Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Lactente , Influenza Humana/tratamento farmacológico , Masculino , Oseltamivir/uso terapêutico , Adulto Jovem
7.
Klin Padiatr ; 224(6): 353-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22821288

RESUMO

BACKGROUND: Risk stratification criteria for patients with Ewing's sarcoma family of tumors (ESFT) are still limited. We hypothesized divergent human leukocyte antigen (HLA) patterns in ESFT patients and compared HLA-A, -B and -DR phenotype frequencies of patients with advanced ESFT with those of healthy controls. PATIENTS: HLA types of all German Caucasian patients with advanced ESFT and available HLA-A, -B and -DR data registered in the European Group for Blood and Marrow Transplantation, Paediatric Registry for Stem Cell Transplantation and the MetaEICESS data bases (study group, n=30) were retrospectively compared with HLA types of healthy German stem cell donors (control group, n=8 862 for single HLA frequencies and n=8 839 for allele combinations). Study group patients had been immuno-typed due to eligibility for allogeneic stem cell transplantation for high risk of treatment failure, and thus constituted a selected subgroup of ESFT patients. RESULTS: After Bonferroni correction for multiple testing (PC), phenotype frequencies of HLA-A24 remained significantly higher in the study group compared to controls (PC<0.05). Furthermore, several HLA combinations were significantly more frequent in the study group compared to controls (all PC<0.05). CONCLUSION: We report an increased incidence of circumscribed HLA patterns in German Caucasians with advanced ESFT. The possible clinical significance of this observation has to be re-assessed in prospective trials comprising larger ESFT patient numbers of all risk groups.


Assuntos
Doadores de Sangue , Transplante de Medula Óssea , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-DR/genética , Transplante de Células-Tronco Hematopoéticas , Sarcoma de Ewing/genética , Sarcoma de Ewing/terapia , Doadores de Tecidos , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Progressão da Doença , Feminino , Frequência do Gene , Genética Populacional , Alemanha , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Estudos Retrospectivos , Sarcoma de Ewing/patologia , Adulto Jovem
8.
Klin Padiatr ; 224(3): 160-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22504775

RESUMO

Despite the implementation of new antifungal drugs, invasive aspergillosis (IA) still remains a considerable challenge in pediatric oncology with a severe mortality. Prophylactic and therapeutic measurement have to be evaluated in these rare but poor prognostic patients. Therefore the entire group of patients at risk of developing IA has to be defined before cooperative prospective trials. In a retrospective analysis including all our patients with malignancies we looked for patients with proven/probable IA. Cases of the period from 2003 to 2008 were analyzed in detail.In the period between 2003 to 2008 24 of 755 patients were affected by proven/ probable IA. Compared to former studies incidence increased from 1.3%in 1980 to 3.4% in 2008. AML patients with or without allogeneic/haploidentical stem cell transplantation were at highest risk (24% and 25% respectively, in comparison to 1% in ALL-patients). Survival after 2 years was 50% for patients with AML and IA. In patients with high risk to develop IA the effect of intensified, intravenous antimycotic prophylaxis has to be proven prospectively in a cooperative and randomized setting.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Infecções Oportunistas/tratamento farmacológico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Administração Oral , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infusões Intravenosas , Aspergilose Pulmonar Invasiva/mortalidade , Aspergilose Pulmonar Invasiva/prevenção & controle , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Masculino , Infecções Oportunistas/mortalidade , Infecções Oportunistas/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Voriconazol
9.
Leukemia ; 26(5): 963-71, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22289921

RESUMO

The purpose of this study was the appraisal of the clinical and functional consequences of germline mutations within the gene for the IL-2 inducible T-cell kinase, ITK. Among patients with Epstein-Barr virus-driven lymphoproliferative disorders (EBV-LPD), negative for mutations in SH2D1A and XIAP (n=46), we identified two patients with R29H or D500T,F501L,M503X mutations, respectively. Human wild-type (wt) ITK, but none of the mutants, was able to rescue defective calcium flux in murine Itk(-/-) T cells. Pulse-chase experiments showed that ITK mutations lead to varying reductions of protein half-life from 25 to 69% as compared with wt ITK (107 min). The pleckstrin homology domain of wt ITK binds most prominently to phosphatidylinositol monophosphates (PI(3)P, PI(4)P, PI(5)P) and to lesser extend to its double or triple phosphorylated derivates (PIP2, PIP3), interactions which were dramatically reduced in the patient with the ITK(R29H) mutant. ITK mutations are distributed over the entire protein and include missense, nonsense and indel mutations, reminiscent of the situation in its sister kinase in B cells, Bruton's tyrosine kinase.


Assuntos
Mutação em Linhagem Germinativa , Herpesvirus Humano 4/fisiologia , Transtornos Linfoproliferativos/virologia , Proteínas Tirosina Quinases/genética , Sítios de Ligação , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mutação de Sentido Incorreto , Linhagem , Fosforilação , Proteínas Tirosina Quinases/metabolismo
10.
Ann Oncol ; 22(7): 1614-1621, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21245159

RESUMO

BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Doença Enxerto-Hospedeiro/terapia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
11.
Pediatr Transplant ; 15(4): E80-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20214747

RESUMO

MHC class II deficiency is a rare and fatal form of primary combined immunodeficiency caused by a lack of T-cell-dependent humoral and cellular immune response to foreign antigens, which can only be cured by allogenic stem cell transplantation. In the literature search, we identified 68 cases of HSCT in MHC class II deficiency in the last 14 yr. Pre- and post-transplant MHC class II deficiency is complicated by overwhelming viral infections, a high incidence of GvHD, and graft failure with a poor overall survival rate below 50%. We report an eight-month-old boy presenting with severe respiratory infections and chronic diarrhea, whose sister died at the age of four yr from septicemia. MHC II deficiency was caused by an RFXANK-mutation and treated successfully by 4/6 mismatched unrelated CBT after a myeloablative conditioning regimen based on anti-thymocyte globulin, busulfane, fludarabine, and cyclophosphamide. At present, our patient is well with full immune reconstitution 3(4/12) yr after CBT. CB may represent an alternative source of stem cells for children with MHC class II deficiency without a suitable donor.


Assuntos
Sangue Fetal/transplante , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos de Histocompatibilidade Classe II/imunologia , Síndromes de Imunodeficiência/cirurgia , Seguimentos , Sobrevivência de Enxerto , Antígenos de Histocompatibilidade Classe II/genética , Teste de Histocompatibilidade , Humanos , Síndromes de Imunodeficiência/diagnóstico , Lactente , Masculino , Medição de Risco , Índice de Gravidade de Doença , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento
12.
AJNR Am J Neuroradiol ; 32(6): E110-2, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20651019

RESUMO

Subacute MTX-induced encephalopathy is characterized by an abrupt onset of focal neurologic deficits within days after intrathecal or systemic therapy. Demyelination is one proposed mechanism. We describe the neuroimaging features of 2 patients with clinical symptoms of subacute encephalopathy after intrathecal and systemic MTX therapy. DWI showed restricted diffusion, indicating cytotoxic edema. MTI yielded no evidence of demyelination in either patient because there was no loss of MTR in areas of restricted diffusion.


Assuntos
Encefalopatias/induzido quimicamente , Encefalopatias/diagnóstico , Doenças Desmielinizantes/diagnóstico , Aumento da Imagem/métodos , Metotrexato/efeitos adversos , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Adolescente , Antimetabólitos Antineoplásicos/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encefalopatias/prevenção & controle , Criança , Doenças Desmielinizantes/induzido quimicamente , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Síndromes Neurotóxicas/prevenção & controle
13.
Biol Blood Marrow Transplant ; 16(10): 1428-35, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20399877

RESUMO

Major advances in the monitoring and treatment of viral infections after hematopoietic stem cell transplantation (HSCT) have been achieved over the last decade. The appropriate extent of viral monitoring and antiviral therapy remains controversial, and reports in pediatric patients receiving allogeneic unmanipulated hematopoietic stem cells (HSCs) are sparse. A total of 40 pediatric patients who underwent HSCT with either peripheral blood stem cells (PBSCs, n = 30) or bone marrow (BM; n = 10) were prospectively monitored every week for viral DNAemia (VDNA) by simultaneous detection of cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV6), human adenovirus (ADV), and polyoma BK virus (BKV) using real-time TaqMan polymerase chain reaction (PCR). All patients received prophylactic acyclovir and preemptive ganciclovir (GCV) when 500 copies/microg DNA (EBV/HHV6) or >1 copy/microg DNA (CMV) were detected on 2 consecutive measurements. VDNA occurred in 25 of 40 recipients (CMV, 11/40 patients [28%]; EBV, 19/40 [48%]; HHV6, 2/40 [5%]; ADV/BKV, 1/40) and was found exclusively after neutrophil engraftment and in most cases up to day +100. Recurrent VDNA (P = .028) and (readily treatable) viral disease (P = .003) were observed predominantly in patients suffering from nonmalignant diseases, a cohort characterized by delayed lymphocyte engraftment. VDNA occurred more frequently in HLA-mismatched HSCT and in the 24 of 40 patients receiving antithymocyte globulin (ATG). The incidence of EBV, but not that of CMV, was increased in the ATG group. Yet, in these patients, viral loads of both EBV and CMV were higher, but with prompt initiation of preemptive GCV, no posttransplantation lymphoproliferative disorder or other life-threatening morbidities occurred. HHV6 was typically detected at low viral loads (<10(2) copies/microg DNA), with only 5% of HSC recipients fulfilling our HHV6 criteria for triggering GCV treatment. In multivariate analysis, ATG treatment, HLA mismatch, recipient CMV seropositivity, and stem cell source, but not severe acute graft-versus-host disease were identified as independent risk factors for VDNA. This comprehensive viral monitoring program with defined thresholds for initiation of preemptive GCV effectively prevents the development of critical viral disease, even in high-risk patients receiving ATG.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Complicações Pós-Operatórias/epidemiologia , Viroses/epidemiologia , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/prevenção & controle , Adolescente , Soro Antilinfocitário , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Vírus BK/isolamento & purificação , Transplante de Medula Óssea/estatística & dados numéricos , Criança , Pré-Escolar , DNA Viral/sangue , Feminino , Ganciclovir/uso terapêutico , Doença Enxerto-Hospedeiro/complicações , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/tratamento farmacológico , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/prevenção & controle , Humanos , Lactente , Masculino , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/tratamento farmacológico , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/prevenção & controle , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Pré-Medicação , Estudos Prospectivos , Transplante Homólogo , Viremia/diagnóstico , Viremia/epidemiologia , Viroses/diagnóstico , Viroses/tratamento farmacológico , Viroses/prevenção & controle , Adulto Jovem
14.
Z Rheumatol ; 69(6): 561-7, 2010 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-20174926

RESUMO

TNF inhibitors and other biologicals have greatly expanded the therapeutic options for juvenile idiopathic arthritis (JIA). While the efficacy of etanercept and adalimumab has been proven in randomized controlled clinical trials, their long-term safety remains the subject of ongoing investigations. Reports of leukaemia and tumours in children and adolescents treated with etanercept, infliximab and adalimumab have raised questions about an increased risk for malignancies, with lymphoma accounting for the largest group at 50% of all 48 malignancies reported by the FDA.Consequently, TNF inhibitors should be indicated under careful consideration of individual risk factors, such as increased family occurrence of malignancies, or pre-treatment with carcinogenic substances such as cyclophosphamide. This is particularly true for non-approved substances, and non-approved indications, and for combination therapy of TNF inhibitors with immunosuppressive drugs. On the other hand, however, treatment should not be stopped or started in any patient in whom treatment is necessary due to the current knowledge. Adequate patient information, surveillance and documentation of treatment in the registry of the GKJR is strongly recommended.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Neoplasias/induzido quimicamente , Sociedades Médicas , Fator de Necrose Tumoral alfa/antagonistas & inibidores , United States Food and Drug Administration , Adolescente , Adulto , Produtos Biológicos/uso terapêutico , Criança , Humanos , Leucemia/induzido quimicamente , Linfoma/induzido quimicamente , Uso Off-Label , Resultado do Tratamento , Estados Unidos , Adulto Jovem
15.
Bone Marrow Transplant ; 45(3): 483-9, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19684633

RESUMO

We examined the role of total body magnetic resonance imaging (TB-MRI)-governed involved compartment irradiation (ICI) and high-dose chemotherapy (HDC), followed by stem cell rescue (SCR) in patients with high-risk Ewing tumors (ETs) with multiple primary bone metastases (high-risk ET-MBM). Eleven patients with high-risk ET-MBM receiving initial assessment of involved bones by TB-MRI were registered from 1995 to 2000 (group A). In all, 6 patients out of 11 had additional lung disease at initial diagnosis; all had multifocal bone disease with more than three bones involved. After systemic induction with etoposide, vincristine, adriamycin (doxorubicin), ifosfamide, and actinomycin D (EVAIA) or VAIA chemotherapy, ICI of all sites positive by TB-MRI was administered, followed by HDC and SCR. A second group matched for observation period and consisting of 26 patients with more than three involved bones at diagnosis was treated with the European Intergroup Cooperative Ewing Sarcoma Study-92 (EICESS-92) protocol (group B). These patients did not receive TB-MRI and consequently did not receive TB-MRI-governed ICI, or HDC and SCR. Survival in group A vs group B was 45 vs 8% at 5 years and 27 vs 8% at 10 years after diagnosis (log rank and Breslow: P<0.005). We conclude that TB-MRI-governed ICI followed by HDC and SCR in ET-MBM is feasible and warrants further evaluation in prospective studies.


Assuntos
Neoplasias Ósseas/terapia , Sarcoma de Ewing/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Criança , Protocolos Clínicos , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/radioterapia , Sarcoma de Ewing/secundário , Irradiação Corporal Total/métodos , Adulto Jovem
16.
Klin Padiatr ; 221(3): 167-71, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19437365

RESUMO

BACKGROUND: Severe hemophilia A (HA) in females is a very rare phenomenon. Ignoring HA as a possible diagnose can result in fatal complications. PATIENTS: We report a 3-month old girl suffering from severe hemophilia A, presenting with intracranial hemorrhage three weeks after drop down from an infant carrier. Recurrent bleeding after neurosurgery led to the diagnosis of a HA by findings of low levels of factor VIII coagulation activity (F8:C) below 1% and normal levels of factor von Willebrand activity. METHODS: Diagnosis of hemophilia A by one stage clotting test and proof by molecular studies via long - range - PCR. Chromosome analysis in metaphases from peripheral blood lymphocytes. RESULTS: Molecular analysis showed inversion of intron 22 as the result of a maternally inherited, distal, F8 gene inversion and chromosome analyses a 45,X karyotype indicative of Turner syndrome in our patient. Diagnosis was hampered by the female sex and the presence of neither a family history of bleeding disorders nor clinical signs of Turner syndrome. CONCLUSION: Our case shows that, although uncommon in female infants, x-linked genetic bleeding disorders like HA are a possible diagnosis by very different reasons. Rare bleeding disorders, although not expected, might be present and the combined clinical, laboratory and genetic analysis are needed to establish the final diagnosis. Repetitive prolonged aPTT and clinical bleeding signs should lead to further hemostasiological investigations. An algorithm for hemostasiological investigations in case of unexplained clinical bleeding is given.


Assuntos
Hemofilia A/diagnóstico , Hemorragias Intracranianas/diagnóstico , Síndrome de Turner/diagnóstico , Inversão Cromossômica/genética , Diagnóstico Diferencial , Fator VIII/administração & dosagem , Feminino , Traumatismos Cranianos Fechados/complicações , Traumatismos Cranianos Fechados/cirurgia , Hematoma Epidural Craniano/diagnóstico , Hematoma Epidural Craniano/cirurgia , Hemofilia A/genética , Humanos , Lactente , Hemorragias Intracranianas/cirurgia , Íntrons/genética , Cariotipagem , Imageamento por Ressonância Magnética , Osso Parietal/lesões , Reação em Cadeia da Polimerase , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/cirurgia , Reoperação , Fraturas Cranianas/diagnóstico , Fraturas Cranianas/cirurgia , Tomografia Computadorizada por Raios X , Síndrome de Turner/genética
17.
J Med Virol ; 80(8): 1461-7, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18551595

RESUMO

Although chronic courses of norovirus infection have been described in immunocompromised patients, little is known about noroviral shedding and correlation with clinical symptoms in these patients. In this report, the quantitative courses of norovirus excretion in nine pediatric patients with hematologic and oncologic disorders and prolonged gastroenteritis were investigated. In a retrospective study multiple fecal samples from nine pediatric cancer patients were examined by a one-step real-time PCR. Clinical data of the patients were reviewed and virological data were correlated with clinical symptoms. All nine patients presented with prolonged illness and prolonged noroviral shedding. Vomiting and diarrhea were associated with high norovirus concentrations and norovirus excretion declined slowly in the patients. Retrospectively, initial PCR-testing for norovirus was performed with a median of 7 days after onset of symptoms. This finding hints at the difficulty of obtaining early diagnosis of the infection in these children. The patients were shedding high norovirus concentration over a long period of time. Results of sequential quantitative PCR-testing for norovirus correlated with clinical symptoms. Both clinical symptoms and quantitative PCR-testings help to define the severity of norovirus infection and to estimate the risk for transmission. To prevent the spread of the disease, usage of virocidal disinfectants and isolation procedures should be maintained as long as patients are positive for noroviruses. Since vomiting is frequent in pediatric patients with oncological conditions, a screening program for rapid detection of norovirus infection in this group of patients should be considered.


Assuntos
Gastroenterite/fisiopatologia , Gastroenterite/virologia , Neoplasias/complicações , Norovirus/isolamento & purificação , Eliminação de Partículas Virais , Adolescente , Infecções por Caliciviridae/fisiopatologia , Infecções por Caliciviridae/transmissão , Infecções por Caliciviridae/virologia , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Genótipo , Humanos , Hospedeiro Imunocomprometido , Lactente , Masculino , Norovirus/classificação , Norovirus/genética , RNA Viral/análise , RNA Viral/isolamento & purificação , Índice de Gravidade de Doença , Fatores de Tempo
18.
Klin Padiatr ; 220(3): 147-52, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18478486

RESUMO

Hematopoietic stem cell transplantation is the only permanent treatment for the hematological manifestations in Fanconi anemia (FA). As FA patients have a dramatically increased intrinsic propensity to develop malignancies later in life and the genotoxic stress afflicted during conditioning advances the manifestation age especially of squamous cell carcinomas, choosing an optimally suited treatment regimen appears critical for long-term, tumor-free survival after stem cell transplantation. Here, we report our experiences in 6 consecutive FA patients transplanted with HLA-matched sibling donors where we combined an established pre-transplantation treatment consisting of thoraco-abdominal irradiation (TAI), cyclophosphamide (CYC) and cyclosporine A graft-versus-host prophylaxis with antibody-mediated IN VIVO T-cell depletion strategies after infusion of the graft. This approach has ensured sustained engraftment with long-term survival and an excellent post transplant performance status without any evidence of secondary malignancies in all six patients after a median follow-up of more than 10 years.


Assuntos
Purging da Medula Óssea/métodos , Anemia de Fanconi/terapia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Depleção Linfocítica/métodos , Linfócitos T/imunologia , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Anemia de Fanconi/imunologia , Anemia de Fanconi/mortalidade , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imunossupressores/uso terapêutico , Irradiação Linfática/métodos , Masculino , Transplante Isogênico
19.
HNO ; 56(3): 312-20, 2008 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-17581692

RESUMO

BACKGROUND: Hemorrhage after tonsillectomy and adenoidectomy remains a serious complication. Therefore, routine preoperative coagulation screening, including activated partial thromboplastin time (aPTT), prothrombin time (PT) and platelet count (PLC), are regularly performed, also for medicolegal reasons. In the recently published statement of the German Society of Otorhinolaryngology, Head and Neck Surgery the need for routine preoperative coagulation screening is discussed, but so far no standardized procedure had been established. According to this statement - at least for children - routine preoperative coagulation screening is not mandatory as long as the thorough medical history provides no evidence for a coagulation disorder ( http://www.hno.org/kollegen/gerinnung_te_ae.html ). The present study was undertaken to determine the occurrence of postoperative hemorrhage on the one hand, and the incidence of abnormal preoperative routine coagulation parameters or pathological anamnesis findings on the other. PATIENTS AND METHODS: In 688 patients, a standardized clinical history was obtained using a questionnaire. Coagulation screening included aPTT, PT, and PLC was also carried out. Bleeding complications were then correlated with anamnesis features and abnormalities in coagulation screening. RESULTS: In 39 (5.7%) of the 688 patients we found abnormal coagulation values, which were confirmed in repeated analyses. In six of these a detailed analysis revealed occult coagulation disorders requiring correction only in the case of bleeding complications who were previously unknown. Fifteen patients were already known to have a coagulation disorder, and the anamnesis identified no additional patient at risk. Thus, 21 patients with coagulation disorders requiring correction in the case of a bleeding complication underwent surgery. However, only eight (38%) of these showed abnormal routine coagulation parameters. Surgical treatment of postoperative hemorrhage was required in 12 patients, all of whom had normal values for aPTT, PT and PLC. CONCLUSION: The frequently performed determination of routine coagulation parameters (aPTT, PT, PLC) is not able to reliably identify relevant coagulation disorders or to predict the risk for postoperative hemorrhagic complications after adenoidectomy or tonsillectomy.


Assuntos
Adenoidectomia/estatística & dados numéricos , Tempo de Tromboplastina Parcial/estatística & dados numéricos , Contagem de Plaquetas/estatística & dados numéricos , Hemorragia Pós-Operatória/diagnóstico , Hemorragia Pós-Operatória/epidemiologia , Tempo de Protrombina/estatística & dados numéricos , Tonsilectomia/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários
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