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1.
Orv Hetil ; 161(3): 103-109, 2020 Jan.
Artículo en Húngaro | MEDLINE | ID: mdl-31928060

RESUMEN

Introduction: Autologous hemopoietic stem cell transplantation remains a promising therapy in certain malignant and non-malignant conditions. The procedure, however, will increase the risk of complications, most notably early and late infections. Aim: To analyze the frequency and spectrum of pathogens in early (<+100 days) post-transplant infections and to evaluate risk factors for mortality. Method: Prospectively collected data from 699 patients undergoing autologous hemopoietic stem cell transplantation between 2007 and 2014 at our center were retrospectively reviewed and analyzed. Results: The median age of 699 patients was 56 (interquartile range: 43-62) years, 54% (376) were male. 25 patients have been transferred to other centers and 19 patients were lost to follow up. Neutropenic fever occurred in 69.8% (488) of patients. In addition, 102 infectious episodes in 96 patients were identified. Most commonly bacteremia occurred (49 episodes) with a median onset of 7 (5-11) days. The majority (33/49) of bacteremias have been observed during the pre-engraftment period. Their incidence proved to be higher in patients with malignant lymphoma compared to individuals with plasma cell disorders (p = 0.0005, OR: 2.41, 95% CI: 1.49-3.99). 12 episodes of viral infections and 8 cases of proven or probable invasive mycoses have been identified. Among the 655 patients with complete follow up, 16 in-hospital deaths (2.4%) occurred, 8 of them were associated with infections. Survival was adversely affected by early infections (p = 0.0001). Conclusion: In autologous stem cell transplantation, microbiologically unconfirmed neutropenic fever is common. Documented early bacteremia, however, is infrequent. Lymphoma patients have a significantly higher chance to develop bloodstream infections compared to individuals with plasma cell disorders. Early infections decrease the chance of survival; thus, an effective prophylaxis and therapy remains of paramount importance. Orv Hetil. 2020; 161(3): 103-109.


Asunto(s)
Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Fiebre/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neutropenia/microbiología , Trasplante Autólogo/efectos adversos , Adulto , Infecciones Bacterianas/mortalidad , Fiebre/epidemiología , Humanos , Hungría/epidemiología , Linfoma , Masculino , Persona de Mediana Edad , Neutropenia/epidemiología , Estudios Retrospectivos
2.
Vox Sang ; 115(1): 18-26, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31667887

RESUMEN

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.
Bone Marrow Transplant ; 55(1): 215-223, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31527815

RESUMEN

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for malignant hematopoietic diseases. Cytokines including transforming growth factor ß1 (TGFß1) play a pivotal role in immune reconstruction, and the development of graft versus host disease (GvHD) or infections. The aim of this study was to investigate the role of TGFB1 gene -1347C>T variant in the outcome of HSCT in a cohort of 409 adult recipient-donor pairs. TGFB1 variant was analysed from genomic DNA with LightCycler hybridisation probe method. In case of myeloablative conditioning, donor TGFB1 genotype correlated with overall survival (60-month OS for CC: 62.1 ± 4.8%; CT: 46.8 ± 4.8%; TT: 35.6 ± 9.3%; p = 0.032), which was independent of age, donor type and GvHD prophylaxis in multivariate analysis (HR:2.35, 95%CI:1.35-4.10, p = 0.003). The cumulative incidence of acute GvHD grade III-IV [CC:10%; CT:17%; TT:24%], and non-relapse mortality was higher in TT-carriers (24-month NRM: CC:24%; CT:26%; TT:46%, p = 0.035). We did not find any association between recipient TGFB1 -1347C>T polymorphism and HSCT outcome. Our results suggest that donor TGFB1 -1347C>T may exert an adverse influence on the outcome of myeloablative conditioning transplantation.

5.
Orv Hetil ; 160(10): 363-369, 2019 Mar.
Artículo en Húngaro | MEDLINE | ID: mdl-30829057

RESUMEN

Although cytomegalovirus is one of the most prevalent viral pathogens on the globe, in immunocompetent individuals infected with cytomegalovirus usually no specific antiviral therapy is required. In the case of impaired T-cell mediated immunity, however, latent infection can reactivate and occasionally a viral disease with organ involvement develops. The number of actually available anti-cytomegalovirus drugs is low, for prophylaxis or treatment ganciclovir, valganciclovir, foscarnet or cidofovir can be administered. The clinical use of these drugs is primarily hampered by their toxicity. In search for new treatment options, only letermovir, a terminase complex inhibitor compound showed appropriate activity and tolerability. In a placebo-controlled clinical trial on prophylactic letermovir in stem cell transplant patients, administration of the active compound resulted in a significant decrease in human cytomegalovirus reactivations as well as in prolonged survival. No toxicity affecting clinical use has been observed. For management of patients being at high risk for cytomegalovirus reactivation, appropriate antiviral strategy should be followed. Antiviral prophylaxis or diagnostics-guided pre-emptive therapy seem to be the most suitable options. Orv Hetil. 2019; 160(10): 363-369.


Asunto(s)
Acetatos/uso terapéutico , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/prevención & control , Quinazolinas/uso terapéutico , Trasplante de Células Madre/efectos adversos , Acetatos/administración & dosificación , Citomegalovirus/efectos de los fármacos , Infecciones por Citomegalovirus/fisiopatología , Foscarnet/uso terapéutico , Ganciclovir/uso terapéutico , Humanos , Huésped Inmunocomprometido , Quinazolinas/administración & dosificación
6.
Orv Hetil ; 160(3): 83-92, 2019 Jan.
Artículo en Húngaro | MEDLINE | ID: mdl-30640526

RESUMEN

Human cytomegalovirus is a DNA virus with a global prevalence of 40-100%. In humans, primary infection is followed by a lifelong latent persistent phase. Even in individuals developing adequate specific immunity, interactions with the resident virus do probably occur. Clinically significant problems, however, appear primarily in immunocompromised hosts. As a result of an impaired T-cell mediated immunity, viral reactivation as well as a viral disease resulting in organ damage can develop. Most severely affected are HIV positive persons in AIDS stage and individuals undergoing solid organ or stem cell transplantation. As vital functions and survival may adversely be affected by cytomegalovirus reactivation and disease, it is of paramount significance to evaluate evident risk factors. Viral reactivation and organ specific disease can be detected by several methods based on conventional and molecular biological and histological diagnostic techniques. An up-to-date management of affected patient groups requires a meticulous assessment of the possible risk for cytomegalovirus infection and development of an adequate antiviral strategy. Orv Hetil. 2019; 160(3): 83-92.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Citomegalovirus/efectos de los fármacos , Huésped Inmunocomprometido , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/inmunología , Humanos , Inmunidad Celular/inmunología
7.
Pathol Oncol Res ; 25(2): 487-492, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29524166

RESUMEN

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.


Asunto(s)
Suero Antilinfocítico/efectos adversos , Bradicardia/inducido químicamente , Inmunosupresores/efectos adversos , Adolescente , Bradicardia/epidemiología , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Lactante , Masculino , Metilprednisolona/uso terapéutico , Estudios Retrospectivos
8.
Pediatr Transplant ; 22(8): e13302, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30345623

RESUMEN

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.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Trastornos Linfoproliferativos/terapia , Nivolumab/uso terapéutico , Trasplante de Células Madre , Antineoplásicos/uso terapéutico , Niño , Citarabina/uso terapéutico , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Proteínas de Fusión bcr-abl/genética , Humanos , Inmunosupresión , Inyecciones Espinales , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Linfoma de Células B/inmunología , Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Periodo Posoperatorio , Inducción de Remisión , Rituximab/uso terapéutico , Trasplante Homólogo , Resultado del Tratamiento
9.
Biol Blood Marrow Transplant ; 24(5): 989-996, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29339271

RESUMEN

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.


Asunto(s)
Complejo de Ataque a Membrana del Sistema Complemento/análisis , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Microangiopatías Trombóticas/etiología , Adolescente , Biomarcadores/análisis , Niño , Preescolar , Enfermedad Injerto contra Huésped , Humanos , Valor Predictivo de las Pruebas , Microangiopatías Trombóticas/diagnóstico , Factores de Tiempo , Activación Viral
10.
J Immunother ; 41(3): 158-163, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29239916

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Especificidad del Receptor de Antígeno de Linfocitos T , Linfocitos T/inmunología , Virosis/etiología , Adolescente , Adulto , Factores de Edad , Antivirales/farmacología , Antivirales/uso terapéutico , Niño , Preescolar , Citocinas/metabolismo , Femenino , Humanos , Inmunoterapia Adoptiva , Lactante , Masculino , Persona de Mediana Edad , Linfocitos T/metabolismo , Donantes de Tejidos , Trasplante Homólogo , Carga Viral , Virosis/diagnóstico , Virosis/terapia
11.
Orv Hetil ; 158(39): 1528-1534, 2017 Oct.
Artículo en Húngaro | MEDLINE | ID: mdl-28942664

RESUMEN

In our days, growing incidence of antibiotic resistant bacteria has become an eminent public health problem. For survival Gram-negative species possess several different tools to withstand antibiotics: they produce degrading and modifying enzymes, decrease their permeability or expel drug molecules. An increasing proportion of severe nosocomial infections are caused by strains resistant to several antimicrobials (multiresistant, extensively resistant or panresistant species). Development of new antibiotic compounds may serve as a possible solution to this problem. Ceftolozane-tazobactam is a new beta-lactam+beta-lactamase-inhibitor combination resistant to most extended spectrum beta-lactamase enzymes showing excellent anti-Pseudomonas activity. It is also effective against strains when beta-lactam resistance is related to porin loss or efflux pump activity. The spectrum of ceftazidime-avibactam also includes carbapenemase-(KPC)-producing Enterobacteriaceae. In addition to novel therapy, an effective infection control system together with the prudent use of antimicrobials (antimicrobial stewardship) is of paramount importance. Orv Hetil. 2017; 158(39): 1528-1534.


Asunto(s)
Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Ceftazidima/uso terapéutico , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Ácido Penicilánico/análogos & derivados , Combinación de Medicamentos , Infecciones por Bacterias Gramnegativas/prevención & control , Humanos , Ácido Penicilánico/uso terapéutico , Tazobactam
12.
Orv Hetil ; 158(27): 1043-1050, 2017 Jul.
Artículo en Húngaro | MEDLINE | ID: mdl-28670985

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/etiología , Anticuerpos Monoclonales Humanizados/administración & dosificación , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Humanos , Microangiopatías Trombóticas/tratamiento farmacológico
13.
Magy Onkol ; 61(1): 75-80, 2017 Mar 08.
Artículo en Húngaro | MEDLINE | ID: mdl-28273191

RESUMEN

Invasive fungal diseases represent an ever changing field within infectology, profoundly affecting daily clinical activities of specialists in haematology. The dynamic development seen in oncohaematology creates novel risk groups of patients, consequently necessitating a re-evaluation of principles in antifungal therapy from time to time. Not even in 2017 may achievements of fungal diagnostics and therapy become a substitute for clinical thinking and adaptation of general guidelines according to local experience. For antifungal management all centres should elaborate appropriate strategies. By creating and operating a multidisciplinary team, decision making can effectively be supported.


Asunto(s)
Antifúngicos/uso terapéutico , Neoplasias Hematológicas/complicaciones , Infecciones Fúngicas Invasoras/complicaciones , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Humanos
14.
Mycoses ; 58 Suppl 5: 29-33, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26449504

RESUMEN

Valid data on the prevalence of serious fungal diseases are difficult to derive as in most countries these conditions are not reportable infections. To assess the burden of these infections in Hungary prevalence estimates from international peer-reviewed papers and population statistics were utilised. In the intensive care unit (ICU) population at least 370 cases of serious yeast and 52 mould infections can be expected yearly. The total number of candidaemia cases may be as high as 1110 annually. In patients with acute leukaemia and recipients of haematopoietic stem cell and solid organ transplants the predicted incidence is more than 55 every year. Recurrent vulvovaginal candidiasis--though not a life-threatening condition--can adversely affect the quality of life of more than 177,000 Hungarian women. According to organisation for economic co-operation and development (OECD), 4.7% of total population older than 15 will suffer from chronic obstructive pulmonary disease (COPD) and 4.4% from asthma, adding another very broad risk group to the aforementioned categories susceptible for mycotic complications. Here more than 17,000 can have severe asthma with fungal sensitisation (SAFS) and more than 13,000 are at risk for developing allergic bronchopulmonary aspergillosis (ABPA). The incidence of dermatomycoses and other superficial fungal infections is even more difficult to assess but--according to international estimations--can affect around 14.3% of the total population. More than 1.6 million Hungarians may suffer from fungal diseases annually, with 33,000 cases being life threatening or very serious. This is an under-recognised problem of special importance for public health.


Asunto(s)
Micosis/epidemiología , Adolescente , Adulto , Alérgenos , Aspergilosis Broncopulmonar Alérgica/epidemiología , Aspergilosis Broncopulmonar Alérgica/microbiología , Asma/epidemiología , Asma/etiología , Asma/microbiología , Candidemia/epidemiología , Candidemia/microbiología , Candidiasis Vulvovaginal/epidemiología , Candidiasis Vulvovaginal/microbiología , Costo de Enfermedad , Dermatomicosis/epidemiología , Dermatomicosis/microbiología , Femenino , Humanos , Hungría/epidemiología , Incidencia , Persona de Mediana Edad , Micosis/microbiología , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Calidad de Vida , Adulto Joven
15.
Orv Hetil ; 155(20): 789-92, 2014 May 18.
Artículo en Húngaro | MEDLINE | ID: mdl-24819188

RESUMEN

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.


Asunto(s)
Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/cirugía , Resistencia a Medicamentos , Trasplante de Células Madre Hematopoyéticas , Adolescente , Anticuerpos Monoclonales/administración & dosificación , Colonoscopía , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Fármacos Gastrointestinales/administración & dosificación , Humanos , Hungría , Inmunosupresores/administración & dosificación , Infliximab , Masculino , Índice de Severidad de la Enfermedad , Trasplante Autólogo , Resultado del Tratamiento
16.
J Antimicrob Chemother ; 68 Suppl 3: iii5-16, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24155144

RESUMEN

Invasive fungal disease (IFD), predominantly aspergillosis, is associated with significant morbidity and mortality in immunocompromised patients, especially those with haematological malignancies and recipients of allogeneic haematopoietic stem cell transplantation. There has been a great deal of scientific debate as to the effectiveness of antifungal prophylaxis in preventing infection in different patient groups and in which patients it is an appropriate management option. Deciding on an appropriate prophylaxis regimen for IFD is challenging as the incidence varies among different patient groups, due to the varied nature of their underlying haematological disease, and in different regions and centres. Attempts have been made to define risk factors and include them in treatment protocols. Impaired immune status of the patient, especially neutropenia, is a key risk factor for IFD and can sometimes be related to specific polymorphisms of genes controlling innate immunity. Risk factors also vary according to the type of fungal pathogen. Consequently, prophylaxis needs to be tailored to individual patient groups. Furthermore, the choice of antifungal agent for prophylaxis depends on the potential for drug-drug interactions with the patients' concomitant medications. Additional challenges are optimal timing of antifungal prophylaxis, when to change from prophylaxis to antifungal treatment and how to prevent recurrence of IFD. This article considers the use of antifungal prophylaxis for patients at risk of IFD in daily clinical practice, with clinical profiles that may be distinct from those covered by guidelines, and aims to provide practical advice for treatment of these patient groups.


Asunto(s)
Antifúngicos/uso terapéutico , Manejo de Caso/organización & administración , Quimioprevención/métodos , Neoplasias Hematológicas/complicaciones , Huésped Inmunocomprometido , Micosis/prevención & control , Medicina de Precisión/métodos , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Medición de Riesgo , Trasplante Homólogo/efectos adversos
17.
Future Microbiol ; 7(10): 1141-6, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23030421

RESUMEN

Twelve months after the WHO launched its global campaign to safeguard current antimicrobial medicines for future generations, antifungal stewardship initiatives were a major focus for the 2012 European Congress of Clinical Microbiology and Infectious Diseases, in London, UK. Speakers from Europe, North and South America and Asia reported significant variations in fungal epidemiology and resistance, and demonstrated the value of multidisciplinary infectious disease advisory teams in monitoring local trends and making recommendations about the most appropriate antifungal treatment.


Asunto(s)
Antifúngicos/administración & dosificación , Farmacorresistencia Fúngica , Quimioterapia/normas , Micosis/tratamiento farmacológico , Micosis/epidemiología , Salud Global , Humanos , Londres , Micosis/microbiología
18.
Metab Brain Dis ; 27(2): 193-6, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22350962

RESUMEN

Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation, delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation (HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable in LNS as well. Following a myeloablative conditioning regimen (busulphan 3.2 mg/kg/day for 4 days, cyclophosphamide 60 mg/kg/day for 2 days with ATG Thymoglobin 2.5 mg/kg/day for 4 days) an unrelated umbilical cord blood unit was transfused at the age of 2 years. The graft was a 6/6 HLA-matched at HLA-A, B loci by antigen level, and at DRB1 by allelic level typing. Infused total nucleated cell dose was 3.6 × 10e7 per kilogram body weight. Serum HPRT levels reached normal values by the end of the sixth month post transplant. Slow neurodevelopmental improvement seen during the three-year follow-up and the missing self-injuring behavior can be considered as a proof for the presence of enzyme-competent cells behind the blood-brain barrier.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Síndrome de Lesch-Nyhan/terapia , Busulfano/uso terapéutico , Desarrollo Infantil , Preescolar , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Ciclofosfamida/uso terapéutico , Distonía/etiología , Antígenos HLA-A/inmunología , Antígenos HLA-B/inmunología , Humanos , Hipoxantina Fosforribosiltransferasa/sangre , Inmunosupresores/uso terapéutico , Síndrome de Lesch-Nyhan/psicología , Masculino , Mucositis/etiología , Mucositis/patología , Espasticidad Muscular/etiología , Neutropenia/etiología , Conducta Autodestructiva/etiología , Conducta Autodestructiva/terapia
19.
Magy Onkol ; 55(3): 155-63, 2011 Sep.
Artículo en Húngaro | MEDLINE | ID: mdl-21918740

RESUMEN

Prognosis of malignant diseases is significantly influenced by infectious morbidity and mortality. Thus, up to date management of cancer patients, in addition to other supportive care modalities, should also incorporate diagnostic methods and therapy of infections. In order to improve outcome, patients developing febrile neutropenia following antitumour treatment should be adequately informed regarding the risk of infections. At the same time, centres responsible for cancer patient care should set up written protocols for basic workup and empirical antibiotic therapy. Here general characteristics of neutropenic infections developing in solid tumour patients are outlined and key points for risk assessment are highlighted. In addition, options and limits of anti-infective therapy as well as prophylaxis of infections are reviewed. Importance of a fully functional institutional infection control system and multidisciplinary patient management is also emphasised.


Asunto(s)
Antiinfecciosos/uso terapéutico , Antineoplásicos/efectos adversos , Infecciones Bacterianas/tratamiento farmacológico , Micosis/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neutropenia/complicaciones , Antibacterianos/uso terapéutico , Antiinfecciosos/administración & dosificación , Antifúngicos/uso terapéutico , Antineoplásicos/administración & dosificación , Infecciones Bacterianas/etiología , Ciprofloxacino/administración & dosificación , Protocolos Clínicos , Esquema de Medicación , Medicina Basada en la Evidencia , Fiebre/microbiología , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Micosis/etiología , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Ofloxacino/administración & dosificación , Grupo de Atención al Paciente , Medición de Riesgo
20.
Haematologica ; 96(11): 1613-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21791467

RESUMEN

BACKGROUND: Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia. DESIGN AND METHODS: Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent. RESULTS: The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P = 0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P = 0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P = 0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P = 0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P = 0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P = 0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P = 0.024) and overall survival (P = 0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype. CONCLUSIONS: Janus kinase 2 46/1 haplotype influences morphological distribution, increasing the predisposition towards an acute myelomonocytoid form. It may be a novel, independent unfavorable risk factor in acute myeloid leukemia with a normal karyotype.


Asunto(s)
Mutación de Línea Germinal , Janus Quinasa 2/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Haplotipos , Humanos , Janus Quinasa 2/metabolismo , Cariotipo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/enzimología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de Supervivencia
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