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1.
Trials ; 21(1): 96, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952545

RESUMO

BACKGROUND: Although there have been multiple randomised trials in newly diagnosed Ewing sarcoma family of tumours (ESFT) and these have been conducted over many years and involved many international cooperative groups, the outcomes for all stages of disease have plateaued. Internationally, the standard treatment of ESFT is not defined, and there is a need to add new agents other than conventional chemotherapy to improve outcomes. This trial will compare two different induction/consolidation chemotherapy regimens: (1) vincristine, ifosfamide, doxorubicin and etoposide (VIDE) induction and vincristine, actinomycin D, ifosfamide or cyclophosphamide, or busulfan and mephalan (VAI/VAC/BuMel) consolidation and (2) vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC/IE) induction and ifosfamide and etoposide, vincristine and cyclophosphamide, vincristine, actinomycin D and ifosfamide, or busulfan and mephalan (IE/VC/VAI/BuMel) consolidation (randomisation 1, or R1). A second randomisation (R2) will determine whether the addition of zoledronic acid to consolidation chemotherapy, as assigned at R1, is associated with improved clinical outcome. METHODS: EURO EWING 2012 is an international, multicentre, phase III, open-label randomised controlled trial. There are two randomisations: R1 and R2. Patients are randomly assigned at two different time points: at entry to the trial (R1) and following local control therapy (R2). The primary outcome measure is event-free survival. The secondary outcome measures include overall survival, adverse events and toxicity, histological response of the primary tumour, response of the primary tumour, regional lymph nodes or metastases (or both), and achievement of local control at the end of treatment. DISCUSSION: This study will establish which is the "standard regimen" of chemotherapy, taking into account both clinical outcomes and toxicity. This will form the chemotherapy backbone for future interventional studies where we may want to add new targeted agents. It will also determine the role of zoledronic acid in conjunction with the separate EE2008 trial. Any trial in ESFT needs to take into account the rarity of the tumour and consider that international cooperation is needed to provide answers in a timely manner. TRIAL REGISTRATION: Registered with EudraCT number 2012-002107-17 on 26 February 2012. Registered with ISRCTN number 54540667 on 4 November 2013.

2.
J Hum Genet ; 65(2): 165-174, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31772335

RESUMO

Somatic mutational mosaicism is a common feature of monogenic genetic disorders, particularly in diseases such as retinoblastoma, with high rates of de novo mutations. The detection and quantification of mosaicism is particularly relevant in these diseases, since it has important implications for genetic counseling, patient management, and probably also on disease onset and progression. In order to assess the rate of somatic mosaicism (high- and low-level mosaicism) in sporadic retinoblastoma patients, we analyzed a cohort of 153 patients with sporadic retinoblastoma using ultra deep next-generation sequencing. High-level mosaicism was detected in 14 out of 100 (14%) bilateral patients and in 11 out of 29 (38%) unilateral patients in whom conventional Sanger sequencing identified a pathogenic mutation in blood DNA. In addition, low-level mosaicism was detected in 3 out of 16 (19%) unilateral patients in whom conventional screening was negative in blood DNA. Our results also reveal that mosaicism was associated to delayed retinoblastoma onset particularly in unilateral patients. Finally we compared the level of mosaicism in different tissues to identify the best DNA source to identify mosaicism in retinoblastoma patients. In light of these results we recommended analyzing the mosaic status in all retinoblastoma patients using accurate techniques such as next-generation sequencing, even in those cases in which conventional Sanger sequencing identified a pathogenic mutation in blood DNA. Our results suggest that a significant proportion of those cases are truly mosaics that could have been overlooked. This information should be taking into consideration in the management and genetic counseling of retinoblastoma patients and families.

3.
Polymers (Basel) ; 11(9)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527526

RESUMO

Boron removal was evaluated in the present work by using calcium alginate beads (CA) and a novel composite based on alginate-alumina (CAAl) as sorbents in a batch system. The effects of different parameters such as pH, temperature, contact time, and composition of alginate (at different concentrations of guluronic and mannuronic acids) on boron sorption were investigated. The results confirm that calcium alginate beads (CA) exhibited a better adsorption capacity in a slightly basic medium, and the composite alginate-alumina (CAAl) exhibited improved boron removal at neutral pH. Sorption isotherm studies were performed and the Langmuir isotherm model was found to fit the experimental data. The maximum sorption capacities were 4.5 mmol g-1 and 5.2 mmol g-1, using CA and CAAl, respectively. Thermodynamic parameters such as change in free energy (ΔG0), enthalpy (ΔH0), and entropy (ΔS0) were also determined. The pseudo-first-order and pseudo-second-order rate equations (PFORE and PSORE, respectively) were tested to fit the kinetic data; the experimental results can be better described with PSORE. The regeneration of the loaded sorbents was demonstrated by using dilute HCl solution (distilled water at pH 3) as eluent for metal recovery.

4.
EBioMedicine ; 47: 156-162, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31427232

RESUMO

BACKGROUND: Up to 30-40% of Ewing sarcoma (EwS) patients with non-metastatic disease develop local or metastatic relapse within a time span of 2-10 years. This is in part caused by the absence of prognostic biomarkers that can identify high-risk patients and thus assign them to risk-adapted monitoring and treatment regimens. Since cancer stemness has been associated with tumour relapse and poor patient outcomes, we investigated in the current study the prognostic potential SOX2 (sex determining region Y box 2) - a major transcription factor involved in development and stemness - which was previously described to contribute to the undifferentiated phenotype of EwS. METHODS: Two independent patient cohorts, one consisting of 189 retrospectively collected EwS tumours with corresponding mRNA expression data (test-cohort) and the other consisting of 141 prospectively collected formalin-fixed and paraffin-embedded resected tumours (validation and cohort), were employed to analyse SOX2 expression levels through DNA microarrays or immunohistochemistry, respectively, and to compare them with clinical parameters and patient outcomes. Two methods were employed to test the validity of the results at both the mRNA and protein levels. FINDINGS: Both cohorts showed that only a subset of EwS patients (16-20%) expressed high SOX2 mRNA or protein levels, which significantly correlated with poor overall survival. Multivariate analyses of our validation-cohort revealed that high SOX2 expression represents a major risk-factor for poor survival (HR = 3·19; 95%CI 1·74-5·84; p < 0·01) that is independent from metastasis and other known clinical risk-factors at the time of diagnosis. Univariate analyses demonstrated that SOX2-high expression was correlated with tumour relapse (p = 0·002). The median first relapse was at 14·7 months (range: 3·5-180·7). INTERPRETATION: High SOX2 expression constitutes an independent prognostic biomarker for EwS patients with poor outcomes. This may help to identify patients with localised disease who are at high risk for tumour relapse within the first two years after diagnosis. FUNDING: The laboratory of T. G. P. Grünewald is supported by grants from the 'Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München (WiFoMed)', by LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the 'Mehr LEBEN für krebskranke Kinder - Bettina-Bräu-Stiftung', the Walter Schulz Foundation, the Wilhelm Sander-Foundation (2016.167.1), the Friedrich-Baur foundation, the Matthias-Lackas foundation, the Barbara & Hubertus Trettner foundation, the Dr. Leopold & Carmen Ellinger foundation, the Gert & Susanna Mayer foundation, the Deutsche Forschungsgemeinschaft (DFG 391665916), and by the German Cancer Aid (DKH-111886 and DKH-70112257). J. Li was supported by a scholarship of the China Scholarship Council (CSC), J. Musa was supported by a scholarship of the Kind-Philipp foundation, and T. L. B. Hölting by a scholarship of the German Cancer Aid. M. F. Orth and M. M. L. Knott were supported by scholarships of the German National Academic Foundation. G. Sannino was supported by a scholarship from the Fritz-Thyssen Foundation (FTF-40.15.0.030MN). The work of U. Dirksen is supported by grants from the German Cancer Aid (DKH-108128, DKH-70112018, and DKH-70113419), the ERA-Net-TRANSCAN consortium (project number 01KT1310), and Euro Ewing Consortium (EEC, project number EU-FP7 602,856), both funded under the European Commission Seventh Framework Program FP7-HEALTH (http://cordis.europa.eu/), the Barbara & Hubertus Trettner foundation, and the Gert & Susanna Mayer foundation. G. Hardiman was supported by grants from the National Science Foundation (SC EPSCoR) and National Institutes of Health (U01-DA045300). The laboratory of J. Alonso was supported by Instituto de Salud Carlos III (PI12/00816; PI16CIII/00026); Asociación Pablo Ugarte (TPY-M 1149/13; TRPV 205/18), ASION (TVP 141/17), Fundación Sonrisa de Alex & Todos somos Iván (TVP 1324/15).

5.
An. pediatr. (2003. Ed. impr.) ; 91(2): 127.e1-127.e10, ago. 2019. tab, graf
Artigo em Espanhol | IBECS-Express | ID: ibc-ET2-3942

RESUMO

La trombocitopenia inmune primaria, anteriormente conocida como púrpura trombocitopénica inmune, es una enfermedad cuyo manejo diagnóstico y terapéutico ha sido siempre controvertido. La Sociedad Española de Hematología y Oncología Pediátricas, a través del grupo de trabajo de la PTI, ha actualizado el documento con las recomendaciones protocolizadas para el diagnóstico y tratamiento de esta enfermedad, basándose en las guías clínicas disponibles actualmente, revisiones bibliográficas, ensayos clínicos y el consenso de sus miembros. El objetivo principal es disminuir la variabilidad clínica en los procedimientos diagnósticos y terapéuticos con el fin de obtener los mejores resultados clínicos, los mínimos efectos adversos y preservar la calidad de vida


Primary immune thrombocytopenia, formerly known as immune thrombocytopenic purpura, is a disease for which the clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of primary immune thrombocytopenia in children, based on current guidelines, bibliographic review, clinical assays, and member consensus. The main objective is to reduce clinical variability in diagnostic and therapeutic procedures, in order to obtain best clinical results with minimal adverse events and good quality of life

6.
Stem Cells Int ; 2019: 8475389, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281387

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease with a very poor prognosis. At the same time, its incidence is on the rise, and PDAC is expected to become the second leading cause of cancer-related death by 2030. Despite extensive work on new therapeutic approaches, the median overall survival is only 6-12 months after diagnosis and the 5-year survival is less than 7%. While pancreatic cancer is particularly difficult to treat, patients usually succumb not to the growth of the primary tumor, but to extensive metastasis; therefore, strategies to reduce the migratory and metastatic capacity of pancreatic cancer cells merit close attention. The vast majority of pancreatic cancers harbor RAS mutations. The outstanding relevance of the RAS/MEK/ERK pathway in pancreatic cancer biology has been extensively shown previously. Due to their high dependency on Ras mutations, pancreatic cancers might be particularly sensitive to inhibitors acting downstream of Ras. Herein, we use a genetically engineered mouse model of pancreatic cancer and primary pancreatic cancer cells were derived from this model to demonstrate that small-molecule MEK inhibitors functionally abrogate cancer stem cell populations as demonstrated by reduced sphere and organoid formation capacity. Furthermore, we demonstrate that MEK inhibition suppresses TGFß-induced epithelial-to-mesenchymal transition and migration in vitro and ultimately results in a highly significant reduction in circulating tumor cells in mice.

7.
An Pediatr (Barc) ; 91(2): 127.e1-127.e10, 2019 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-31178291

RESUMO

Primary immune thrombocytopenia, formerly known as immune thrombocytopenic purpura, is a disease for which the clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of primary immune thrombocytopenia in children, based on current guidelines, bibliographic review, clinical assays, and member consensus. The main objective is to reduce clinical variability in diagnostic and therapeutic procedures, in order to obtain best clinical results with minimal adverse events and good quality of life.


Assuntos
Púrpura Trombocitopênica Idiopática/terapia , Qualidade de Vida , Criança , Humanos , Púrpura Trombocitopênica Idiopática/diagnóstico
8.
Int J Drug Policy ; 72: 189-194, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31160156

RESUMO

BACKGROUND: Prisoners and other high-risk patients who show a sustained virological response (SVR) after treatment for hepatitis C virus (HCV) can become reinfected. We aimed to calculate the rate of HCV reinfection in a large cohort of inmates with SVR and to determine factors that predict reinfection. METHODS: We included all inmates treated for hepatitis C in Catalonia (Spain) from January 2002 to December 2016 who achieved SVR and in whom viral load was subsequently determined. The incidence rate was calculated per 100 person-years (100 py) of follow up. Risk factors associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression. Hazard ratio (HR) and their 95% confidence intervals (CI) were calculated. RESULTS: 602 patients were included, with a mean age of 37.9 years: 95% were men, 74.1% had a history of intravenous drug use (IDU) and 28.7% were HIV-infected. Patients were followed for a total of 2154.9 years (average 3.58 ± 3.1 years). 63 (10.5%) had HCV reinfection. 41 (65.1%) presented different genotype/subgenotype, 8 the initial genotype/subgenotype, and in 14 (22.2%) the genotype could not be determined. Of the 21 reinfected patients who were interviewed, 20 (95.2%) reported IDU after antiviral treatment, and 7 (33.3%) during treatment. The overall incidence of reinfection was 2.9 cases per 100 py. All reinfections occurred in patients with IDU history. At multivariate level, HIV infection was associated with reinfection (HR = 3.03; CI:1.82-5.04). CONCLUSION: In HIV-infected inmates with IDU history, the rate of reinfection of HCV post-SVR is very high. Prisons play a key role in the detection and treatment of infection and reinfection by HCV and in the post-treatment monitoring in these patients, which should be combined with counseling and the optimization of the harm reduction programs. Effective control of these vulnerable groups favours the elimination of the HCV infection.

9.
Pancreatology ; 19(4): 541-547, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31109903

RESUMO

OBJECTIVES: The importance of the Calcitonin-gene-related-peptide-pathway (CGRP) as neuronal modulator of innate immune responses in mice has been previously demonstrated. The CGRP-receptor is composed of two subunits: the receptor-activity-modifying-protein-1 (RAMP1) and the calcitonin-receptor-like-receptor (CLR). CGRP can influence immune cells and their capacity of producing inflammatory cytokines. Using a RAMP1 knockout-mouse (RAMP1-/-) we examined the role of the CGRP-receptor in the acute-phase of cerulein-induced pancreatitis. METHODS: Hourly cerulein-injections for a period of 8 h in RAMP1-/- and wild-type mice were performed. To compare severity and extent of inflammation in RAMP1-/- and wild-type mice, histological analyses were done and cytokine levels were assessed using qRT-PCR 8 h, 24 h, 2 days, and 7 days post-cerulein-treatment. Furthermore, serum activities of LDH and lipase were determined. RESULTS: After 8 h RAMP1-/- mice showed a higher pancreas-to-body-weight-ratio, increased tissue edema and immune cell infiltration with higher amount of F4/80-positive cells as compared to wild-type mice. Overall infiltration of immune cells at 24 h was increased in RAMP1-/- mice and composed predominantly of MPO-positive neutrophils. In addition, after 24 h RAMP1-/- mice presented a higher pancreas-to-body-weight-ratio, higher expression of Ccl3, Il6, and Il1b and increased number of cleaved caspase 3 positive cells. Serum lipase correlated with the extent of tissue damage in RAMP1-/- compared to wild-type mice 24 h post-cerulein treatment. CONCLUSION: Mice lacking RAMP1 showed increased inflammation, tissue edema, and pancreas injury particularly in the early phase of acute pancreatitis. This study highlights the essential role of CGRP for dampening the innate immune response in acute pancreatitis.


Assuntos
Imunidade Inata/genética , Pancreatite/genética , Pancreatite/imunologia , Proteína 1 Modificadora da Atividade de Receptores/genética , Doença Aguda , Animais , Ceruletídeo , Citocinas/sangue , Feminino , Inflamação/induzido quimicamente , Inflamação/patologia , L-Lactato Desidrogenase/metabolismo , Lipase/análise , Lipase/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos , Tamanho do Órgão , Pancreatite/induzido quimicamente , Proteína 1 Modificadora da Atividade de Receptores/imunologia
10.
Front Immunol ; 10: 586, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984175

RESUMO

Background: Immunodeficiencies (ID), in particular primary immunodeficiencies (PID), are often associated with haematological manifestations, such as peripheral cytopenias or lymphoproliferative syndromes. Early diagnosis and management have significant prognostic implications. Secondary immunodeficiencies (SID) may also be induced by oncohaematological diseases and their treatments. Haematologists and oncologists must therefore be aware of the association between blood disorders and cancer and ID, and be prepared to offer their patients appropriate treatment without delay. Our aim was to define the warning signs of primary and secondary IDs in paediatric and adult patients with oncohaematological manifestations. Methods: A multidisciplinary group of six experts (2 haematologists, 2 immunologists, and 2 paediatricians specializing in ID) conducted a literature review and prepared a document based on agreements reached an in-person meeting. An external group of 44 IDs specialists from all over Spain assessed the document and were consulted regarding their level of agreement. Results: This document identifies the haematological and extra-haematological diseases that should prompt a suspicion of PIDs in adults and children, in both primary care and haematology and oncology departments. Cytopenia and certain lymphoproliferative disorders are key diagnostic pointers. The diagnosis must be based on a detailed clinical history, physical exploration, complete blood count and standard laboratory tests. The immunological and haematological tests included in the diagnostic process will depend on the care level. Patients who are candidates for immunoglobulin replacement therapy must be carefully selected, and treatment should be offered as soon as possible to avoid the development of complications. Finally, this document recommends procedures for monitoring these patients. Conclusions: This document combines scientific evidence with the opinion of a broad panel of experts, and emphasizes the importance of an early diagnosis and treatment to avoid complications. The resulting document is a useful tool for primary care physicians and specialists who see both adult and paediatric patients with oncohaematological diseases.

11.
Polymers (Basel) ; 11(2)2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30960324

RESUMO

A new composite material based on alginate and magadiite/Di-(2-ethylhexyl) phosphoric acid (CAM-D2EHPA) was successfully prepared by previous impregnation of layered magadiite with D2EHPA extractant, and then immobilized into the alginate matrix. Air dried beads of CAM-D2EHPA were characterized by FTIR and SEM⁻EDX techniques. The sorbent was used for the separation of lead and nickel from nitrate solutions; the main parameters of sorption such as contact time, pH of the solution, and initial metal concentration were studied. The beads recovered 94% of Pb(II) and 65% of Ni(II) at pH 4 from dilute solutions containing 10 mg L-1 of metal (sorbent dosage, S.D. 1 g L-1). The equilibrium data gave a better fit using the Langmuir model, and kinetic profiles were fitted using a pseudo-second order rate equation. The maximum sorption capacities obtained (at pH 4) were 197 mg g-1 and 44 mg g-1 for lead and nickel, respectively. The regeneration of the sorbent was efficiently carried out with a dilute solution of HNO3 (0.5 M). The composite material was reused in 10 sorption⁻elution cycles with no significant differences on sorption uptake. A study with synthetic effluents containing an equimolar concentration of both metals indicated a better selectivity towards lead ions.

12.
Polymers (Basel) ; 11(2)2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30960335

RESUMO

The presence of antimony(III) in water represents a worldwide concern, mainly due to its high toxicity and carcinogenicity potential. It can be separated from water by the use of sustainable biopolymers such as chitosan or its derivatives. The present study applied chitosan modified with iron(III) beads to Sb(III) removal from aqueous solutions. The resulting material performed with a high adsorption capacity of 98.68 mg/g. Material characterization consisted of Raman spectroscopy (RS), X-ray diffraction (XRD), scanning electron microscope observations (SEM-EDX), Fourier transform infrared spectroscopy (FTIR) and point of zero charge (pHpzc). The adsorption study included pH study, effect of initial concentration, kinetics, ion effect, and reusability assessment. The RS, XRD, and FTIR results indicated that the main functional groups in the composite were related to hydroxyl and amino groups, and iron oxyhydroxide species of α-FeO(OH). The pHpzc was found to be 7.41. The best adsorption efficiency was set at pH 6. The equilibrium isotherms were better fitted with a non-linear Langmuir model, and the kinetics data were fitted with a pseudo-second order rate equation. The incorporation of iron into the chitosan matrix improved the Sb(III) uptake by 47.9%, compared with neat chitosan (CS). The material did not exhibit an impact in its performance in the presence of other ions, and it could be reused for up to three adsorption⁻desorption cycles.

13.
Med. clín (Ed. impr.) ; 152(4): 135-145, feb. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-181880

RESUMO

Antecedentes y objetivos: El incremento descrito en la prevalencia de hemoglobinopatías, de ß-talasemia mayor (TM) y de enfermedad drepanocítica (ED) que ha ocurrido en las últimas dos décadas en nuestro país ha generado nuevas necesidades en cuanto a recursos médicos tanto para la prevención como para el tratamiento de estos pacientes. El trasplante alogénico de progenitores hematopoyéticos (alo-TPH) es el tratamiento curativo disponible en nuestro medio para pacientes con hemoglobinopatías graves. El objetivo principal de este estudio fue conocer los resultados del alo-TPH en pacientes pediátricos con TM o ED realizados en unidades de trasplante hematopoyético pediátrico incluidas dentro del Grupo Español de Trasplante de Médula Ósea en Niños (GETMON). Material y métodos: Revisión retrospectiva de los pacientes sometidos a TPH en unidades de TPH del GETMON hasta el año 2015. Resultados: Se analizaron un total de 65 pacientes (43 pacientes afectados de TM y 22 de ED) que recibieron el alo-TPH en 6 unidades GETMON entre noviembre de 1989 y diciembre de 2014. La supervivencia libre de eventos 3años postrasplante fue del 81% y la supervivencia global del 92% en pacientes con TM. La supervivencia libre de eventos 3años postrasplante fue del 79% y la supervivencia global del 85% en pacientes con ED. Conclusiones: Los resultados de esta serie son comparables a los resultados de otras series internacionales y ofrecen un punto de partida para continuar intentando mejorar la evolución de estos pacientes


Background and objectives: A recently occurring increase of the prevalence of haemoglobinopathies, ß-thalassaemia major (TM) and sickle cell disease (SCD) over the last two decades in our country has generated new needs in terms of medical resources for both prevention and treatment of these patients. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is a curative treatment available for patients who have severe haemoglobinopathies. The main objective of this study was to evaluate the results of allo-HSCT in paediatric patients with TM or SCD performed in paediatric hematopoietic transplant units within the Spanish Group of Bone Marrow Transplantation in Children (GETMON). Material and methods: Retrospective review of patients undergoing HSCT in the GETMON units until 2015. Results: A total of 65 patients were analysed (43 patients were affected with TM and 22 with SCD), who received allo-HSCT in 6 GETMON units between November 1989 and December 2014. Event-free survival three years post-transplant was 81% and overall survival 92% in patients with TM. Event-free survival three years post-transplant was 79% and overall survival 85% in patients with SCD. Conclusions: The results of this series are comparable to the results of other international series and offer a platform from which to continue trying to improve the evolution of these patients


Assuntos
Humanos , Transplante de Células-Tronco Hematopoéticas , Talassemia/epidemiologia , Hemoglobinopatias/epidemiologia , Transplante Homólogo/métodos , Neutrófilos/transplante , Hemoglobinopatias/prevenção & controle , Hemoglobinopatias/terapia , Estudos Retrospectivos , Sociedades Médicas/normas , Doença Enxerto-Hospedeiro , Sobrevivência
14.
Am J Transplant ; 19(6): 1798-1805, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30586230

RESUMO

We report data obtained from a retrospective multicenter pediatric survey on behalf of the European Society for Blood and Marrow Transplantation (EBMT). Information on solid organ transplantation (SOT) performed in pediatric recipients of either autologous or allogeneic hematopoietic stem cell transplantation (HSCT) between 1984 and 2016 was collected in 20 pediatric EBMT Centers (25.6%). Overall, we evaluated data on 44 SOTs following HSCT including 20 liver (LTx), 12 lung (LuTx), 6 heart (HTx), and 6 kidney (KTx) transplantations. The indication for SOT was organ failure related to intractable graft-vs-host disease in 16 children (36.3%), acute or chronic HSCT-related toxicity in 18 (40.9%), and organ dysfunction related to the underlying disease in 10 (22.8%). The median follow-up was 10.9 years (95% confidence interval: 1.7-29.5). The overall survival rate at 1 and 5 years after SOT was 85.7% and 80.4%, respectively: it was 74% and 63.2% after LTx, 83.2% after HTx, and 100% equally after LuTx and KTx. This multicenter survey confirms that SOT represents a promising option in children with severe organ failure occurring after HSCT. Additional studies are needed to further establish the effectiveness of SOT after HSCT and to better understand the mechanism underlying this encouraging success.

15.
Med Clin (Barc) ; 152(4): 135-140, 2019 02 15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30001893

RESUMO

BACKGROUND AND OBJECTIVES: A recently occurring increase of the prevalence of haemoglobinopathies, ß-thalassaemia major (TM) and sickle cell disease (SCD) over the last two decades in our country has generated new needs in terms of medical resources for both prevention and treatment of these patients. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is a curative treatment available for patients who have severe haemoglobinopathies. The main objective of this study was to evaluate the results of allo-HSCT in paediatric patients with TM or SCD performed in paediatric hematopoietic transplant units within the Spanish Group of Bone Marrow Transplantation in Children (GETMON). MATERIAL AND METHODS: Retrospective review of patients undergoing HSCT in the GETMON units until 2015. RESULTS: A total of 65 patients were analysed (43 patients were affected with TM and 22 with SCD), who received allo-HSCT in 6 GETMON units between November 1989 and December 2014. Event-free survival three years post-transplant was 81% and overall survival 92% in patients with TM. Event-free survival three years post-transplant was 79% and overall survival 85% in patients with SCD. CONCLUSIONS: The results of this series are comparable to the results of other international series and offer a platform from which to continue trying to improve the evolution of these patients.

16.
An. pediatr. (2003. Ed. impr.) ; 89(3): 189.e1-189.e8, sept. 2018. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-177094

RESUMO

La trombocitopenia inmune (PTI) es una entidad relativamente frecuente en pediatría. Aunque su evolución suele ser favorable en la mayoría de los casos, el manejo de aquellos pacientes en los que la enfermedad persiste es muy controvertido. Este artículo pretende, a través de una revisión de la literatura más reciente, responder a aspectos relacionados con el tratamiento de la PTI persistente, crónica y refractaria durante la infancia, haciendo especial énfasis en el papel del rituximab, la esplenectomía y los análogos de la trombopoyetina (ar-TPO) en la infancia. La aparición de los ar-TPO (eltrombopag y romiplostim) amplía el arsenal terapéutico de la PTI pediátrica. Además, tras haber demostrado un perfil de seguridad adecuado en ensayos clínicos, retrasa la indicación de esplenectomía o el uso de tratamientos asociados a mayor riesgo de complicaciones, como rituximab. No obstante, se recomienda que su manejo sea supervisado por centros con experiencia de cara a monitorizar complicaciones potenciales a medio y largo plazo ya descritas en el paciente adulto


Immune thrombocytopenia (ITP) is a relatively common disorder in childhood. Although it usually achieves spontaneous remission at this age, the management of persistent or chronic ITP in children is still controversial. The aim of this article is to address current controversies related to the treatment of persistent, chronic, and refractory ITP in children, including the role of rituximab and splenectomy, as well as focusing on a new approach with thrombopoietin receptor agonists (TPO-RAs). Eltrombopag and romiplostim are safe and useful drugs for paediatric ITP. These two TPO-RAs might delay surgery and other treatments such as rituximab. However, the potential side effects described in adult patients should be considered. Paediatric patients with refractory ITP, undergoing new treatments, should be supervised in specialised centres


Assuntos
Humanos , Lactente , Trombocitopenia/imunologia , Trombopoetina/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/administração & dosagem , Fatores de Risco , Receptores de Trombopoetina/agonistas
17.
An Pediatr (Barc) ; 89(3): 189.e1-189.e8, 2018 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-30033108

RESUMO

Immune thrombocytopenia (ITP) is a relatively common disorder in childhood. Although it usually achieves spontaneous remission at this age, the management of persistent or chronic ITP in children is still controversial. The aim of this article is to address current controversies related to the treatment of persistent, chronic, and refractory ITP in children, including the role of rituximab and splenectomy, as well as focusing on a new approach with thrombopoietin receptor agonists (TPO-RAs). Eltrombopag and romiplostim are safe and useful drugs for paediatric ITP. These two TPO-RAs might delay surgery and other treatments such as rituximab. However, the potential side effects described in adult patients should be considered. Paediatric patients with refractory ITP, undergoing new treatments, should be supervised in specialised centres.


Assuntos
Púrpura Trombocitopênica Idiopática/terapia , Criança , Doença Crônica , Árvores de Decisões , Humanos , Púrpura Trombocitopênica Idiopática/diagnóstico
18.
Biol Blood Marrow Transplant ; 24(11): 2316-2323, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30031939

RESUMO

The CD45RA T cell depletion (TCD) method has been used to deplete naive T cells, preventing graft-versus-host disease (GVHD) but preserving memory cells, providing immediate functional T cells with anti-infection, antileukemia, and antirejection effects. We describe a series of 25 consecutive high-risk patients with leukemia who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with CD45RA TCD. Each patient received 2 cell products: 1 created by CD34 positive selection and the other through CD45RA depletion from the CD34 negative fraction by a CliniMACS device. CD45RA-depleted haplo-HSCT was well tolerated, with rapid engraftment and low risk of severe acute GVHD and chronic GVHD. Although this treatment achieved a good control of viral reactivations, such as cytomegalovirus and adenovirus, we observed an unexpectedly high rate of limbic encephalitis due to human herpesvirus-6 (HHV-6; 8 cases). Characteristically, the infection appeared early in almost all patients, just after the engraftment. Although no patient died from encephalitis, 1 patient showed neuropsychological sequelae, and another experienced secondary graft failure just after the HHV-6 reactivation.


Assuntos
Encefalite Viral/etiologia , Herpesvirus Humano 6/patogenicidade , Linfócitos T/metabolismo , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Pré-Escolar , Encefalite Viral/patologia , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Masculino
19.
Oncotarget ; 9(33): 22907-22914, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29796161

RESUMO

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Numerous studies have shown that microRNAs (miRNAs) could play a role in this disease. Nowadays, more than 2500 miRNAs have been described, that regulate more than 50% of genes, including those involved in B-cell maturation, differentiation and proliferation. Genetic variants in miRNAs can alter their own levels or function, affecting their target gene expression, and then, may affect ALL risk. Therefore, the aim of this study was to determine the role of miRNA genetic variants in B-ALL susceptibility. We analyzed all variants in pre-miRNAs (MAF > 1%) in two independent cohorts from Spain and Slovenia and inferred their functional effect by in silico analysis. SNPs rs12402181 in miR-3117 and rs62571442 in miR-3689d2 were associated with ALL risk in both cohorts, possibly through their effect on MAPK signalling pathway. These SNPs could be novel markers for ALL susceptibility.

20.
An. pediatr. (2003. Ed. impr.) ; 88(4): 196-203, abr. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-172989

RESUMO

Introducción: El trasplante de progenitores hematopoyéticos (TPH) consiste en implantar elementos celulares capaces de generar un sistema hematopoyético nuevo y sano. El régimen de intensidad reducida (RIR) consiste en un tratamiento predominantemente inmunosupresor, para facilitar un implante progresivo con menor morbilidad. Este tipo de acondicionamiento puede también provocar mielosupresión, aunque potencialmente reversible en el tiempo. El acondicionamiento RIR permite aplicar TPH a pacientes con enfermedad genética en los que no es deseable añadir comorbilidad por las altas dosis de quimioterapia que conlleva el régimen mieloablativo convencional. Pacientes y métodos: Se analiza la evolución de 68 pacientes pediátricos con enfermedades genéticas que entre los años 2005-2013 se han sometido a un TPH con RIR en las Unidades pediátricas de Trasplante Hematopoyético de los hospitales españoles integrantes del Grupo Español para Trasplante de Médula Ósea en niños. Se trata de un estudio multicéntrico que incluye a 68 pacientes, de los cuales 43 presentan inmunodeficiencia primaria, 21 presentan hemopatía congénita y 4 están afectados de metabolopatía. Resultados: Cincuenta de los 68 pacientes se encuentran vivos (73,5%). La supervivencia global (SG) a 9 años es de 0,74. Veintitrés (33,8%) han presentado en el transcurso del TPH algún evento. Supervivencia libre de evento de 0,66. La SG en los pacientes con hemopatía es de 0,81; en las inmunodeficiencias primarias es de 0,70 y en las metabolopatías es de 0,4. No se observa diferencia significativa entre los 3 grupos de enfermedades. Respecto a la fuente de progenitores hematopoyéticos, la SG en los pacientes trasplantados con sangre periférica es de 0,74; con médula ósea es de 0,70 y con la sangre de cordón umbilical es de 0,70. No se observa tampoco diferencia estadística significativa. Conclusiones: En nuestro trabajo, de ámbito nacional, hemos evidenciado unos resultados favorables en TPH con régimen de intensidad reducida en las enfermedades genéticas. Cabe destacar que las metabolopatías requieren una consideración individualizada para sopesar en cada paciente los riesgos y beneficios que comporta el RIR


Introduction: Haematopoietic stem cell transplantation (HSCT) involves implanting cellular elements capable of generating a new and healthy haematopoietic system. Reduced intensity conditioning (RIC) consists of an immunosuppressive treatment to facilitate a progressive implant with lower morbidity. This type of conditioning can also lead to myelosuppression, which is potentially reversible over time. Reduced intensity conditioning enables HSCT to be performed on patients with genetic diseases for whom added comorbidity is undesirable due to the high doses of chemotherapy that accompanies conventional myeloablative regimens. Patients and methods: An analysis was performed on the outcomes of 68 paediatric patients with genetic diseases who underwent HSCT with RIC between 2005 and 2013 in the of Paediatric Haematopoietic Stem Cell Transplantation Units that are part of the Spanish Working Group for Bone Marrow Transplantation in Children. A multicentre study was conducted including 68 patients, of whom 43 had Primary Immunodeficiency, 21 with congenital haematological diseases, and 4 with metabolic diseases. Results: Fifty (73.5%) of the 68 patients were still alive. The Overall Survival (OS) at nine years was 0.74. Twenty-three (33.8%) had some event during the course of the HSCT, with an event-free survival rate of 0.66. The OS in patients with haematological diseases was 0.81, being 0.7 in primary immunodeficiencies, and 0.4 in metabolic diseases. No significant difference was observed between the 3 groups of diseases. As regards the source of haematopoietic progenitors, there was an OS rate of 0.74 in patients transplanted with peripheral blood, 0.70 with bone marrow, and 0.70 and with cord blood, with no statistically significant differences. Conclusions: Favourable results have been obtained in HSCT with reduced intensity conditioning in genetic diseases. It should be noted that the risks and benefits of the RIC in patients with metabolic diseases need to be assessed on an individual basis


Assuntos
Humanos , Masculino , Feminino , Criança , Transplante de Medula Óssea/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Doenças Genéticas Inatas/complicações , Condicionamento Pré-Transplante/métodos , Comorbidade , Estudos Retrospectivos , Estudos Prospectivos
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