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1.
Infect Dis Ther ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667696

RESUMO

INTRODUCTION: Immunocompromised patients infected with influenza exhibit prolonged viral shedding and higher risk of resistance. Optimized treatment strategies are needed to reduce the risk of antiviral resistance. This phase IIIb, randomized, double-blind study (NCT00545532) evaluated conventional-dose or double-dose oseltamivir for the treatment of influenza in immunocompromised patients. METHODS: Patients with primary or secondary immunodeficiency and influenza infection were randomized 1:1 to receive conventional-dose oseltamivir (75 mg adolescents/adults [≥ 13 years]; 30-75 mg by body weight in children [1-12 years]) or double-dose oseltamivir (150 or 60-150 mg, respectively), twice daily for an extended period of 10 days. Nasal/throat swabs were taken for virology assessments at all study visits. Co-primary endpoints were safety/tolerability and viral resistance. Secondary endpoints included time to symptom alleviation (TTSA) and time to cessation of viral shedding (TTCVS). RESULTS: Of 228 patients enrolled between February 2008 and May 2017, 215 (199 adults) were evaluable for safety, 167 (151 adults) for efficacy, and 152 (138 adults) for resistance. Fewer patients experienced an adverse event (AE) in the conventional-dose group (50.5%) versus the double-dose group (59.1%). The most frequently reported AEs were nausea, diarrhea, vomiting, and headache. Fifteen patients had post-baseline resistance, more commonly in the conventional-dose group (n = 12) than in the double-dose group (n = 3). In adults, median TTSA was similar between arms, while median TTCVS was longer with conventional dosing. CONCLUSIONS: Oseltamivir was well tolerated, with a trend toward better safety/tolerability for conventional dosing versus double dosing. Resistance rates were higher with conventional dosing in this immunocompromised patient population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00545532. FUNDING: F. Hoffmann-La Roche Ltd.

2.
Vox Sang ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667887

RESUMO

BACKGROUND AND OBJECTIVES: Administration of virus-specific T cells (VSTs) is a viable antiviral treatment strategy after allogeneic HSCT, even if conventional therapies fail. Third-party donors are often chosen for the generation of the VST product. The eligibility of the donor has to be tested in a rigorous donor screening procedure, since the isolation technology only targets pre-existing VSTs. MATERIALS AND METHODS: In a period of 3 years, we performed 32 VST treatments for 28 patients. Targeting four different viruses, 284 healthy individuals underwent 417 donor screening procedures. VSTs were counted by flow cytometry detecting interferon-gamma (IFN-γ) producing T cells. Generation of the VSTs was performed from leukapheresis products in a fully automated and closed system using magnetic cell separation. RESULTS: The mean circulating VST frequencies ranged from 0·006% to 0·328%. The average yield of viable VSTs in the product was 1·83·106 cells, while the average VST dose calculated for the patient's body weight was 4·63·104 /kg. The mean purity - percentage of VSTs within the T cells - of all T-cell products was 62·9%. Correlation was identified between the frequency of the VSTs in the peripheral blood of the donor and the VST numbers of the end product; the strongest correlation was seen for CMV. CONCLUSION: This paper focuses on the T-cell donors, highlighting some key points on the donor selection process. Based on the findings in connection with the CMV therapies, peripheral VST seems to be the best predictor of the VST content of the final product administered to the patient.

3.
Immunotherapy ; 11(12): 1057-1065, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31268374

RESUMO

Aim: This pooled analysis evaluated the safety and tolerability of the subcutaneous immunoglobulin 20% product, Ig20Gly, in primary immunodeficiency diseases using data from two Phase II/III studies conducted in North America and Europe. Patients & materials/methods: Patients received Ig20Gly (volumes, ≤60 ml/site; rates, ≤60 ml/h/site). Adverse events (AEs), tolerability and infusion parameters were assessed. Results: Patients (2-83 years; N = 122) received 6676 Ig20Gly infusions. No causally related serious or severe AEs were reported. Thirty-five patients (28.7%) reported 232 causally related local AEs. Twenty-seven patients (22.1%) reported 165 causally related systemic AEs. There was no association between the infusion volume or rate and causally related local AEs. Conclusion: Ig20Gly was well tolerated in a broad population of patients with primary immunodeficiency diseases.

5.
J Allergy Clin Immunol ; 143(6): 2238-2253, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30660643

RESUMO

BACKGROUND: CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium species infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT). OBJECTIVE: We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. METHODS: We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables' relevance with respect to survival and cure. RESULTS: Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 78.2%, 58.1%, and 72.3% 5 years after HSCT. Results were better in transplantations performed in 2000 or later and in children less than 10 years old at the time of HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT at 2 years or less from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC), and bone marrow-derived stem cells. Most rejections occurred after reduced-intensity or nonmyeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was 50% or greater donor in 85.2%. CONCLUSION: HSCT is curative in patients with CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS, and DFS. Prospective studies are required to compare the risks of HSCT with those of lifelong supportive therapy.

6.
Magy Onkol ; 62(4): 230-236, 2018 Dec 12.
Artigo em Húngaro | MEDLINE | ID: mdl-30540865

RESUMO

The survival of children treated with Ewing sarcoma at Semmelweis University were investigated. Pediatric patients with Ewing sarcoma treated at Semmelweis University from 2001 through 2013 were analyzed in terms of overall survival and clinical factors (age, primary localization and extent of the tumor, time interval from primary complaints to diagnosis). For statistical analysis Kaplan-Meier estimated survival and log rank test were applied. Mean age and follow-up time of the 78 patients were 11.16 and 6.29 years, respectively. In 57% of patients time interval from primary symptoms to diagnosis was less than half year. In 53.8% of the patients the disease was metastatic at primary diagnosis (pulmonary only: 29.5%, any other: 24.3%). 5- and 10-year overall survival of patients were 68.1% and 60.4%, respectively. Among the analyzed factors, the presence of metastasis impaired 5-year overall survival significantly (88.5% for localized disease, 63.5% for pulmonary only and 40.9% for any other metastasis). The survival rate of pediatric patients with Ewing sarcoma treated at Semmelweis University is similar to the result in Western European countries.


Assuntos
Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Adolescente , Fatores Etários , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , Hospitais Universitários , Humanos , Hungria , Estimativa de Kaplan-Meier , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Sarcoma de Ewing/patologia , Fatores Sexuais , Análise de Sobrevida
7.
Orv Hetil ; 159(42): 1710-1719, 2018 10.
Artigo em Húngaro | MEDLINE | ID: mdl-30334483

RESUMO

INTRODUCTION: Acquired bone marrow failures are rare but fatal diseases in childhood. Since 2013, Hungary has been participating as a full member in the work of the European Working Group on uniform diagnostics and therapy in patients with acquired bone marrow failure syndromes. Hypocellular refractory cytopenia of childhood has been emphasized as a frequent entity, transplanted by reduced intensity conditioning with excellent outcomes. AIM: To analyse and compare the results of treatment before and after our joining. METHOD: A total of 55 patients have been treated in the 8 centres of the Hungarian Pediatric Oncology Network during 5 years between 2013 and 2017 (severe aplastic anemia: 9, myelodysplastic syndrome: 41, juvenile myelomonocytic leukemia: 5 patients). Allogeneic hematopoietic stem cell transplantation was performed in severe aplastic anemia in 7 cases, while antithymocyte globulin was administered in one case and one patient died before diagnosis. In patients with myelodysplastic syndromes, watch and wait strategy was applied in 4, while transplantation in 37 cases. Reduced intensity conditioning was used in 54 percent of these cases. Transplantation was the treatment of choice in all 5 patients with juvenile myelomonocytic leukemia. RESULTS: In the whole patient cohort, the time from diagnosis to treatment was median 92 (3-393) days, while in severe aplastic anemia median 28 (3-327) days only. Grade II-IV acute graft versus host disease occurred in 22.6%, grade III-IV in 6.8% and chronic in 11.2%. All the patients treated with severe aplastic anemia are alive and in complete remission (100%). The overall estimated survival rate is 85.1% in myelodysplastic syndrome, while 75% in juvenile myelomonocytic leukemia. The median follow-up was 30.4 (1.1-62.5) months. There was a remarkable increase in overall survival comparing the data before (1992-2012) and after (2013) joining the international group, 70% vs. 100% (p = 0.133) in severe aplastic anemia and 31.3% vs. 85.1% (p = 0.000026) in myelodysplastic syndrome. CONCLUSION: Due to a change in the paradigm of the conditioning regimen in hypocellular refractory cytopenia of childhood, the overall survival rate has significantly increased. Orv Hetil. 2018; 159(42): 1710-1719.

8.
Pediatr Transplant ; 22(8): e13302, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30345623

RESUMO

Primary CNS PTLD is an extremely rare complication after allogeneic HSCT. At our centre, an 11-year-old patient developed nausea, vomiting, and diplopy on day +82 following HSCT. On brain MRI, multiple white matter lesions were seen. Histology showed a diffuse large B-cell lymphoma with high load of EBV in tissue. Despite stopping immunosuppression, treatment with EBV-specific cytotoxic T cells, systemic rituximab, HD-MTX, and intrathecal chemotherapy, progression was observed. With a combination of HD-MTX and cytarabine, only a partial response could be achieved. Having all conventional modalities not only failed but resulted in significant toxicity, a salvage monotherapy with biweekly nivolumab has been instituted. The starting dose was 1.1 mg/kg, later escalated to 2.2 mg/kg. After 8 months of nivolumab therapy, PET-CT showed complete metabolic remission. Subsequently, the patient has been switched to a maintenance dosage of 1.1 mg/kg. No cytopenias, graft failure, GvHD, or any other alloimmune complications were seen during nivolumab therapy. In conclusion, nivolumab may be considered as an effective and safe option for CNS PTLD therapy when all other modalities have failed.

9.
Pathol Oncol Res ; 2018 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-29524166

RESUMO

In antithymocyte globulin (ATG) treated patients occasionally bradycardia has been noticed. Therefore, we retrospectively analyzed the occurrence of bradycardia in ATG-treated children. Using medical records between 2007 and 2012 we identified children undergoing a combined therapy with ATG and glucocorticoids (ATG group, n = 22). The incidence of bradycardia was compared to that registered in children treated with glucocorticoids alone (glucocorticoid alone group, n = 21). Heart rates (HR) were registered before and on days 0-3, 4-7 and 8-14 after the ATG or steroid administration. The rate of bradycardic episodes was higher during ATG therapy than in the steroid alone group, while severe bradycardia occurred only in the ATG group (97 versus 32, p = 0.0037, and 13 versus 0, p = 0.0029, respectively). There was an interaction between the time and treatment group on HR (p = 0.046). Heart rates in ATG and steroid alone groups differed significantly on day 0-3 and day 4-7 (p = 0.046, p = 0.006, respectively). Within the ATG group HR was lower on days 4-7 compared to the days before and the days 8-14 values (p < 0.001, 95%CI: 0.020-0.074). These findings indicate that transient asymptomatic bradycardia is probably more common with ATG therapy than previously reported. HR should be closely monitored during and after ATG therapy.

11.
Biol Blood Marrow Transplant ; 24(5): 989-996, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29339271

RESUMO

Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is a multifactorial complication, and its prediction is largely unresolved. Our aim was to analyze changes of complement profile after HSCT to identify potential markers of TA-TMA development. Thirty-three consecutive pediatric patients (9.6 ± 4.4 years old) who underwent allogeneic HSCT due to malignant (n = 17) or nonmalignant (n = 16) indications were included in this study. Graft-versus-host disease (GVHD) was diagnosed using Glucksberg criteria, viral reactivation was monitored, 5 different TA-TMA diagnostic criteria were applied, and all important clinical and laboratory parameters of TA-TMA activity were registered. Complement pathway activities, components and terminal pathway activation marker (sC5b-9) levels were systematically measured before transplantation and on days 28, 56, and 100 after HSCT. During the first 100 days after HSCT, 1 of 33 patients died (day 50, multiple organ failure), whereas 10 subjects met the criteria for TA-TMA, typically on day 61 (range, 16 to 98 days). TA-TMA was preceded by acute GVHD in 3 of 10 patients, by viral reactivation in 2 of 10, or by both in 4 of 10 cases. Baseline sC5b-9 levels did not differ in patients without (200 [interquartile range, 144 to 266] ng/mL), or with (208 [interquartile range, 166 to 271] ng/mL) subsequent TA-TMA; however, on day 28 significant differences were observed (201 [interquartile range, 185 to 290] ng/mL versus 411 [interquartile range, 337 to 471] ng/mL; P = .004). Importantly, all 10 patients with TMA showed increase in sC5b-9 level from baseline level to day 28, whereas in patients without TMA the same tendency was observed for only 9 of 23 patients (P = .031). No additional complement parameters were closely associated with the development of TA-TMA. Development of TA-TMA occurred in 30% of our patients, typically after GVHD and/or viral reactivation. However, early raise of sC5b-9 activation marker was predictive for later development of TA-TMA, and should therefore be considered as an alarming sign necessitating a careful monitoring of all TA-TMA activity markers. Further studies enrolling a higher number of patients are necessary to determine if terminal pathway activation is an independent predictor of TA-TMA.

12.
J Immunother ; 41(3): 158-163, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29239916

RESUMO

Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350-786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

13.
Am J Clin Exp Immunol ; 6(5): 76-83, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29181272

RESUMO

Immunoglobulin replacement therapy (IRT) is standard treatment for patients with primary immunodeficiency (PID). Because most of the patients with PID will require long life-time immunoglobulin replacement therapy, the quality of the prescribed products is of utmost importance. The IRT is generally administered either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG). Both routes have been demonstrated to be effective. The preferred route may vary at different times during a given patient's life. Options are therefore not fixed and the choice of route for immunoglobulin therapy will depend on several factors, including patient characteristics, clinical indication, venous access, side effects, rural or remote location, treatment compliance and patient preference. Many years ago, immunoglobulin therapy was associated with side effects which may compromise patient's compliance and quality of life of the patients. Most of the side effects were related to impurities. Recently, major advances in the manufacturing process have been made and new processes, such as the Quality by design (QbD) approach were added into the manufacturing steps to ensure patients tolerability and safety. Due to the improved purity of the immunoglobulin products obtained by these processes, the incidence of side effects is lower, while the ways of administration of Ig therapy and the choice of the regimen has widened to suit patient's preference and needs.

14.
J Clin Immunol ; 37(6): 539-547, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28711959

RESUMO

This multicentre, open-label, prospective, single-arm study was designed to evaluate the efficacy, pharmacokinetics, and safety of IqYmune®, a highly purified 10% polyvalent immunoglobulin preparation for intravenous administration in patients with primary immunodeficiency. IqYmune® was administered to 62 patients (aged 2-61 years) with X-linked agammaglobulinemia or common variable immune deficiency at a dose from 0.22 to 0.97 g/kg every 3 to 4 weeks for 12 months with an infusion rate up to 8 mL/kg/h. A pharmacokinetic study was performed at steady state between the 8th and the 9th infusion. A single case of serious bacterial infection was observed, leading to an annualized rate of serious bacterial infections/patient (primary endpoint) of 0.017 (98% CI: 0.000, 0.115). Overall, 228 infections were reported, most frequently bronchitis, chronic sinusitis, nasopharyngitis and upper respiratory tract infection. The mean annualized rate of infections was 3.79/patient. A lower risk of infections was associated with an IgG trough level > 8 g/L (p = 0.01). The mean annualized durations of absence from work or school and of hospitalization due to infections were 1.01 and 0.89 days/patient, respectively. The mean serum IgG trough level before the 6th infusion was 7.73 g/L after a mean dose of IqYmune® of 0.57 g/kg. The pharmacokinetic profile of IqYmune® was consistent with that of other intravenous immunoglobulins. Overall, 15.5% of infusions were associated with an adverse event occurring within 72 h post infusion. Headache was the most common adverse event. In conclusion, IqYmune® was shown to be effective and well tolerated in patients with primary immunodeficiency.


Assuntos
Agamaglobulinemia/terapia , Imunodeficiência de Variável Comum/terapia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia/métodos , Adolescente , Adulto , Agamaglobulinemia/imunologia , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Imunodeficiência de Variável Comum/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Europa (Continente) , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Imunoglobulinas Intravenosas/farmacocinética , Imunoterapia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
15.
Orv Hetil ; 158(27): 1043-1050, 2017 Jul.
Artigo em Húngaro | MEDLINE | ID: mdl-28670985

RESUMO

Hematopoietic stem cell transplantation associated thrombotic microangiopathy is a multifactorial complication, and has variable incidence in study populations due to different diagnostic criteria. The diversity of activity parameters, like elevated laktát-dehidrogenáz, hematological parameters and kidney function are not specific variables after stem cell transplantation. Dysregulation of the classical and alternative pathway can play an important role in the pathomechanism of thrombotic microangiopathy, but the understanding of the role of complement activation under transplantation conditions requires further investigation. Monitoring of complement parameters, including terminal complement pathway activation complex during transplantation may help physicians to improve diagnostic strategy, to evaluate therapeutical options and to predict and follow up efficacy of complement blockade methods and supportive therapy. This review focuses on the development of diagnostic criteria and therapeutical options in thrombotic microangiopathy, and presents some preliminary findings while using different diagnostic criteria in pediatric patients. Orv Hetil. 2017; 158(27): 1043-1050.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Microangiopatias Trombóticas/tratamento farmacológico
17.
Orv Hetil ; 155(20): 789-92, 2014 May 18.
Artigo em Húngaro | MEDLINE | ID: mdl-24819188

RESUMO

The biological therapy of Crohn's disease, such as infliximab is a powerful approach in the therapy of inflammatory bowel diseases. However, in some patients with aggressive disease course, even a combined immunosuppressive therapy will not result in permanent remission. Hematopoietic stem cell transplantation has emerged as a new potential therapeutic tool for inflammatory bowel diseases. The authors report the case of a 15-year-old boy with severe Crohn's disease resistant to combined immunosuppressive therapy. After a 3-years course of unsuccessful conventional therapy including infliximab, autologous hematopoietic stem cell transplantation was performed which resulted in a complete remission. One year after transplantation the patient has relapsed, but he could be treated effectively with conventional therapy regiments. To the best of knowledge of the authors, this is the first report in Hungary presenting hematopoietic stem cell therapy in patient with severe Crohn's disease.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Resistência a Medicamentos , Transplante de Células-Tronco Hematopoéticas , Adolescente , Anticorpos Monoclonais/administração & dosagem , Colonoscopia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Fármacos Gastrointestinais/administração & dosagem , Humanos , Hungria , Imunossupressores/administração & dosagem , Infliximab , Masculino , Índice de Gravidade de Doença , Transplante Autólogo , Resultado do Tratamento
18.
Orv Hetil ; 155(10): 389-95, 2014 Mar 09.
Artigo em Húngaro | MEDLINE | ID: mdl-24583560

RESUMO

Hemophagocytic lymphohistiocytosis is a multisystem inflammation, generated by the uncontrolled and excessive activation of cytotoxic T lymphocytes and natural killer cells. Severe immunodeficiency and generalized macrophage activation can often be detected in the background of this life threatening disorder. It is classified as a primary immunodeficiency. Functional abnormalities of the perforin protein or defects in granule secretory mechanisms are caused by gene mutations in most cases. Diagnostic criteria of hemophagocytic lymphohistiocytosis are the following: fever, splenomegaly, cytopenias affecting at least two of the 3 lineages in peripheral blood, hypertriglyceridemia and hyperferritinemia, elevated serum level of soluble interleukin-2 receptor (sCD25), hypofibrinogenemia, hemophagocytosis in bone marrow and decreased cytotoxic T cell and natural killer cell activity. In this case report the authors summarize the utility of functional flow cytometry in the diagnosis of hemophagocytic lymphohistiocytosis. Using flow cytometry, elevated intracellular perforin content, decreased killing activity of cytotoxic T cells and natural killer cells, and impaired cell surface expression of CD107a (LAMP1 protein) from in vitro stimulated blood lymphocytes were detected. Abnormal secretion of perforin was also demonstrated. Genetic testing revealed mutation of the MUNC 13-4 gene, which confirmed the base of the abnormal flow cytometric findings. This case report demonstrates the value of functional flow cytometry in the rapid diagnosis of genetically determined hemophagocytic lymphohistiocytosis, a condition in which early diagnosis is critical for optimal management. The authors emphasize the significance of functional flow cytometry in the differential diagnosis of immunodeficiencies.


Assuntos
Citometria de Fluxo , Células Matadoras Naturais/metabolismo , Linfo-Histiocitose Hemofagocítica/diagnóstico , Perforina/metabolismo , Ciclosporina/uso terapêutico , Diagnóstico Diferencial , Evolução Fatal , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Linfócitos/metabolismo , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/metabolismo , Linfo-Histiocitose Hemofagocítica/terapia , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Mutação , Perforina/genética
19.
Orv Hetil ; 155(8): 313-8, 2014 Feb 23.
Artigo em Húngaro | MEDLINE | ID: mdl-24534879

RESUMO

INTRODUCTION: Among possible complications of transplantation the post-transplant lymphoproliferative disease due to immunosuppressive therapy is of paramount importance. In most cases the direct modulating effect of Epstein-Barr virus on immune cells can be documented. AIM: The aim of the authors was to evaluate the incidence os post-transplant lymphoproliferative diseases in pediatric transplant patients in Hungary. METHOD: The study group included kidney, liver and lung transplant children followed up at the 1st Department of Pediatrics, Semmelweis University, Budapest and stem cell transplant children at Szent László Hospital, Budapest. Data were collected from 78 kidney, 109 liver and 17 lung transplant children as well as from 243 children who underwent allogenic stem cell transplantation. RESULTS: Between 1998 and 2012, 13 children developed post-transplant lymphoproliferative disorder (8 solid organ transplanted and 5 stem cell transplanted children). The diagnosis was based on histological findings in all cases. Mortality was 3 out of the 8 solid organ transplant children and 4 out of the 5 stem cell transplant children. The highest incidence was observed among lung transplant children (17.6%). CONCLUSIONS: These data indicate that post-transplant lymphoproliferative disease is a rare but devastating complication of transplantation in children. The most important therapeutic approaches are reduction of immunosuppressive therapy, chemotherapy and rituximab. Early diagnosis may improve clinical outcome and, therefore, routine polymerase chain reaction screening for Epstein-Barr virus of high risk patients is recommended.


Assuntos
Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Transplante de Órgãos/efeitos adversos , Adolescente , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Esquema de Medicação , Diagnóstico Precoce , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Hungria/epidemiologia , Imunossupressores/administração & dosagem , Incidência , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Transplante de Pulmão/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/mortalidade , Masculino , Transplante de Órgãos/mortalidade , Transplante de Órgãos/estatística & dados numéricos , Reação em Cadeia da Polimerase , Rituximab , Transplante de Células-Tronco , Transplante Homólogo
20.
J Perinat Med ; 40(4): 433-8, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22752776

RESUMO

OBJECTIVE: The objective of the study was to assess the efficacy and safety of subcutaneously (SC) and intramuscularly (IM) administered BT088 (Fovepta) human hepatitis B immunoglobulin in neonates of hepatitis B surface antigen (HBs/HBsAg)-positive mothers in the prevention of hepatitis B infection. METHODS: This was an open, prospective, multicenter trial, in which infants were randomized to receive a single SC or IM dose of BT088 (200 IU, 0.4 mL) within 12 h of birth simultaneously with active vaccination against hepatitis B. The primary efficacy variable was the response rate, defined as the proportion of infants whose anti-HBs concentration was negative at predose and ≥100 IU/L 48 to 72 h postdose. RESULTS: The full analysis set included 31 neonates (17 SC and 14 IM). Response was experienced by 30 (96.8%) of 31 infants who received BT088 by either route of administration. The median postdose anti-HBs concentration was 261.2 IU/L. One neonate had a postdose anti-HBs level lower than 100 IU/L (81.0 IU/L). No infant experienced seroconversion during the 7- to 15-month follow-up. BT088 was well tolerated, with no allergic-like, or injection-site reactions observed. CONCLUSION: SC and IM administration of 200 IU (0.4 mL) BT088 resulted in protective serum anti-HBs titers within 72 h of administration in newborn infants and was well tolerated and effective.


Assuntos
Hepatite B/prevenção & controle , Imunoglobulinas/administração & dosagem , Portador Sadio , Feminino , Hepatite B/imunologia , Hepatite B/transmissão , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Humanos , Imunoglobulinas/efeitos adversos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Injeções Intramusculares , Injeções Subcutâneas , Masculino , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Vacinação
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