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1.
Orphanet J Rare Dis ; 15(1): 241, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907615

RESUMO

BACKGROUND: Lung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed. METHODS: Among 1482 children (< 15 years) registered in the French LCH registry (1994-2018), 111 (7.4%) had lung involvement. This retrospective study included data for 17 (1.1%) patients that required one or more intensive care unit (ICU) admissions for respiratory failure. RESULTS: The median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease. First-line vinblastine-corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine: n = 7; etoposide-aracytine: n = 3; targeted therapy n = 2). A total of 6 children (35%) died (repeated pneumothorax: n = 3; diffuse micronodular lung infiltration in the context of multisystem disease: n = 2; following lung transplantation: n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging. CONCLUSIONS: Severe lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.

2.
Br J Haematol ; 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32700439

RESUMO

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO-) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO- LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3-19·7 years) and the median follow-up after was 5·4 years (range, 0·6-15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO- LCH. Appropriate management of induced immune deficiency is mandatory.

3.
Biol Blood Marrow Transplant ; 26(12): 2285-2291, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32007639

RESUMO

Graft-versus-host disease (GVHD) is an important challenge and a major cause of morbidity and mortality in children after hematopoietic stem cell transplant (HSCT). Herein we report our institution's experience of goal-oriented Bayesian monitoring for cyclosporine (CsA) used alone as GVHD prophylaxis during the post-transplant period in pediatric patients with thalassemia major (TM) or sickle cell anemia (SCA) undergoing HLA-matched HSCT. We also studied evolution of chimerism. Twenty-six consecutive patients (SCA, 14; TM, 12) underwent matched sibling donor (MSD) HSCT from 2004 to 2014. All patients received a myeloablative conditioning regimen. GVHD prophylaxis consisted of 20 mg/kg antithymocyte globulin in the conditioning regimens and then CsA alone in the post-transplant period. Target CsA trough blood concentration (TBC) was 150 ± 20 ng/mL. At last follow-up, all patients were alive and free of disease, even in cases of mixed chimerism. Engraftment occurred in all patients. No patient developed grades II to IV acute GVHD, 4 patients developed acute grade I skin GVHD, and only 1 presented with chronic pulmonary GVHD. A better control of GVHD and immunosuppression by a strict monitoring of CsA TBC as described herein is promising and could play a crucial role. Further investigations are required, but this study opens new perspectives to improve survival and safety of HSCT from alternative donors in TM and SCA to levels compatible with that obtained with MSDs.

4.
Eur J Oncol Nurs ; 38: 1-7, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30717930

RESUMO

PURPOSE: Immunosuppressive therapy following pediatric hematopoietic stem cell transplantation is essential for the patient's prognosis, as the antibioprophylaxis and the isolation measures. But medication adherence is suboptimal for children and adolescents, from 52 to 73% in literature. The aim of this study is to provide an understanding of medication adherence after pediatric allogeneic stem cell transplantation (SCT), by identifying facilitators and barriers. METHOD: Semi-structured interviews were conducted by a pharmacist with caregivers and healthcare providers in a pediatric centre. Four topics were discussed: transplantation, post-transplantation therapies, caregivers' experience and the healthcare system. Interviews were audiotaped, transcribed and analysed by inductive approach. FINDINGS: Semi-structured interviews with 15 caregivers and 21 healthcare providers identified factors of medication adherence and hygiene measures. The long-term nature of therapy and difficult transitions of care were identified as major barriers. Recognizing the benefits of medication and parental involvement are facilitators. Furthermore, caregivers expressed the need to take into consideration the family entity. They would like also to receive earlier information from healthcare providers before hospital discharge. Those needs were not always identified by healthcare providers. CONCLUSION: This analysis revealed barriers and facilitators to the medication adherence and to the care. It demonstrated similarities and differences between caregivers and healthcare providers' perceptions and has thereby initiated an improvement process of the healthcare system. As part of this process, medical and paramedical healthcare providers at this French pediatric centre are currently working on a support program for post-alloSCT hospital-home transition.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Adesão à Medicação , Adolescente , Fatores Etários , Atitude do Pessoal de Saúde , Cuidadores , Criança , Feminino , Pessoal de Saúde , Humanos , Imunossupressores/uso terapêutico , Masculino , Pais , Alta do Paciente , Pesquisa Qualitativa
5.
Br J Haematol ; 183(4): 608-617, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30421536

RESUMO

Neurodegenerative (ND) complications in Langerhans cell histiocytosis (LCH) are a late-onset but dramatic sequelae for which incidence and risk factors are not well defined. Based on a national prospective registry of paediatric LCH patients, we determined the incidence rate of clinical ND LCH (cND-LCH) and analysed risk factors, taking into account disease extent and molecular characteristics. Among 1897 LCH patients, 36 (1·9%) were diagnosed with a cND-LCH. The 10-year cumulative incidence of cND-LCH was 4·1%. cND-LCH typically affected patients previously treated for a multisystem, risk organ-negative LCH, represented in 69·4% of cND-LCH cases. Pituitary gland, skin and base skull/orbit bone lesions were more frequent (P < 0·001) in cND-LCH patients compared to those without cND-LCH (respectively 86·1% vs. 12·2%, 75·0% vs. 34·2%, and 63·9% vs. 28·4%). The 'cND susceptible patients' (n = 671) i.e., children who had experienced LCH disease with pituitary or skull base or orbit bone involvement, had a 10-year cND risk of 7·8% vs. 0% for patients who did not meet these criteria. Finally, BRAFV 600E status added important information among these cND susceptible patients, with the 10-year cND risk of 33·1% if a BRAFV 600E mutation was present compared to 2·9% if it was absent (P = 0·002).


Assuntos
Histiocitose de Células de Langerhans/epidemiologia , Doenças Neurodegenerativas/epidemiologia , Sistema de Registros , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Histiocitose de Células de Langerhans/metabolismo , Histiocitose de Células de Langerhans/patologia , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Fatores de Risco
6.
Pediatr Blood Cancer ; 64(8)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28097791

RESUMO

BACKGROUND: Sickle cell anaemia (SCA) is a severe hereditary haemoglobinopathy characterised by haemorheological abnormalities, which play a role in the occurrence of several acute and chronic clinical complications. While ßS -haplotypes and alpha-thalassaemia modulate SCA clinical severity, their effects on blood rheology have been incompletely described. The aim of this study was to test the effects of these genetic modifiers on the haemorheological properties and clinical complication of children with SCA. PROCEDURE: Steady-state haemorheological profile, biological parameters, ßS -haplotypes, alpha-globin status, vaso-occlusive crisis (VOC) and acute chest syndrome frequencies were analysed in 128 children (aged 5 to 18 years) with SCA. RESULTS: Patients with alpha-thalassaemia showed increased red blood cell (RBC) deformability and aggregation compared to those without. Median VOC rate was higher in patients with homozygous alpha-thalassaemia compared to those with a normal alpha genotype. Conversely, the haemorheological profile and clinical complications were not influenced by the ßS -haplotypes in our study. CONCLUSION: Our results demonstrate that alpha-thalassaemia is associated with higher risk for VOC events in children with SCA, which may be due in part to its effects on RBC deformability and aggregation.


Assuntos
Anemia Falciforme/complicações , Eritrócitos/patologia , Talassemia alfa/complicações , Síndrome Torácica Aguda/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Reologia
7.
Eur J Haematol ; 98(3): 296-301, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27981643

RESUMO

OBJECTIVES: Because of the increased hemolytic rate, a significant proportion of patients with sickle cell disease (SCD) are prone to develop cholelithiasis. The present study investigated the role of several genetic factors (UGT1A1 promoter (TA)n repeat polymorphism, alpha-globin status), hematological parameters, clinical severity, and hydroxyurea (HU) therapy on the occurrence of cholelithiasis in SCD. METHODS: One hundred and fifty-eight children (2-18 yr old) regularly followed at the University Hospital of Lyon (France) were included. A multivariate Cox model was used to test the associations between cholelithiasis and the different parameters analyzed. RESULTS: We confirmed that alpha-thalassemia and low basal reticulocyte (RET) count were independent protective factors for cholelithiasis while 7/7, 8/8 and 7/8 UGT1A1 (TA)n genotypes were independent predisposing factors for this complication. We also showed for the first time that HU treatment decreased the risk for cholelithiasis while frequent vaso-occlusive crises and acute chest syndrome events increased that risk. CONCLUSIONS: Our findings demonstrate that UGT1A1 (TA)n polymorphism is not the only factor triggering gallstone formation in SCD. Cholelithiasis is also modulated by RET count, the number of deleted alpha-genes, HU therapy and the frequency of vaso-occlusive events.


Assuntos
Alelos , Anemia Falciforme/complicações , Anemia Falciforme/genética , Colelitíase/etiologia , Genótipo , Glucuronosiltransferase/genética , Adolescente , Biomarcadores , Criança , Pré-Escolar , Colelitíase/diagnóstico , Colelitíase/epidemiologia , Feminino , Humanos , Incidência , Leucócitos , Masculino , Estudos Retrospectivos , Fatores de Risco , alfa-Globinas/genética
8.
J Clin Oncol ; 34(25): 3023-30, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27382093

RESUMO

PURPOSE: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined. PATIENTS AND METHODS: BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae. RESULTS: Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAF(V600E) mutation. Patients with BRAF(V600E) manifested more severe disease than did those with wild-type BRAF. Patients with BRAF(V600E) comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung-involved LCH (P < .001). BRAF(V600E) mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAF(V600E) more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001). CONCLUSION: In children with LCH, BRAF(V600E) mutation was associated with high-risk features, permanent injury, and poor short-term response to chemotherapy. Further population-based studies should be undertaken to confirm our observations and to assess the impact of BRAF inhibitors for this subgroup of patients who may benefit from targeted therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Corticosteroides/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Criança , Pré-Escolar , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos , Feminino , França/epidemiologia , Histiocitose de Células de Langerhans/enzimologia , Histiocitose de Células de Langerhans/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sistema de Registros , Vimblastina/administração & dosagem
10.
PLoS One ; 11(6): e0158182, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27355589

RESUMO

OBJECTIVES: Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown. MATERIALS AND METHODS: Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients. RESULTS: Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age. CONCLUSION: The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.


Assuntos
Fatores Etários , Anemia Falciforme/sangue , Hemoglobina C/biossíntese , Hemorreologia , Adolescente , Adulto , Viscosidade Sanguínea , Criança , Pré-Escolar , Estudos Transversais , Agregação Eritrocítica/efeitos dos fármacos , Deformação Eritrocítica , Feminino , Voluntários Saudáveis , Hematócrito , Humanos , Hidroxiureia/uso terapêutico , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Viscosidade , Adulto Jovem
11.
Clin Hemorheol Microcirc ; 62(2): 173-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26444610

RESUMO

Red blood cell (RBC) deformability is severely decreased in patients with sickle cell anemia (SCA), which plays a role in the pathophysiology of the disease. However, investigation of RBC deformability from SCA patients demands careful methodological considerations. We assessed RBC deformability by ektacytometry (LORRCA MaxSis, Mechatronics, The Netherlands) in 6 healthy individuals and 49 SCA patients and tested the effects of different heights of the RBC diffraction patterns, obtained by altering the camera gain of the LORRCA, on the result of RBC deformability measurements, expressed as Elongation Index (EI). Results indicate that the pattern of RBCs from control subjects adopts an elliptical shape under shear stress, whereas the pattern of RBCs from individuals with SCA adopts a diamond shape arising from the superposition of elliptical and circular patterns. The latter represent rigid RBCs. While the EI measures did not change with the variations of the RBC diffraction pattern heights in the control subjects, we observed a decrease of EI when the RBC diffraction pattern height is increased in the SCA group. The differences in SCA EI values measured at 5 Pa between the different diffraction pattern heights correlated with the percent of hemoglobin S and the percent of sickled RBC observed by microscopy. Our study confirms that the camera gain or aperture of the ektacytometer should be used to standardize the size of the RBC diffraction pattern height when measuring RBC deformability in sickle cell patients and underscores the potential clinical utility of this technique.


Assuntos
Anemia Falciforme/sangue , Deformação Eritrocítica/efeitos dos fármacos , Eritrócitos Anormais/citologia , Eritrócitos/citologia , Testes Hematológicos/normas , Testes Hematológicos/métodos , Hemoglobina Falciforme/análise , Humanos , Estresse Mecânico
12.
Eur J Haematol ; 96(4): 404-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26072930

RESUMO

The aim of this study was to test the association between hematological/genetic factors and cerebral vasculopathy in children with sickle cell anemia (SCA). A group with cerebral vasculopathy (VASC) was composed of children who had stroke (n = 6), silent infarct (n = 11), or an abnormal transcranial Doppler (n = 5). Eighty-four patients had neither positive history of stroke or silent infarct, nor abnormal transcranial Doppler (NORM group). An intermediate group (COND; n = 15) was composed of SCA children with a conditional transcranial Doppler. Biological analyses were performed on samples obtained at steady state and before the beginning of any chronic treatment. The comparisons of the three groups demonstrated a protective effect of α-thalassemia against cerebral vasculopathy through its effects on hemoglobin and reticulocyte levels. Moreover, we observed higher frequency of G6PD deficiency in the VASC group compared with the other groups. Our study confirms the key role of α-thalassemia and G6PD status in the pathophysiology of cerebral vasculopathy in SCA children.


Assuntos
Anemia Falciforme/diagnóstico , Transtornos Cerebrovasculares/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Talassemia alfa/diagnóstico , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/patologia , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/patologia , Criança , Pré-Escolar , Feminino , Deficiência de Glucosefosfato Desidrogenase/sangue , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/patologia , Hemoglobinas/metabolismo , Humanos , Masculino , Contagem de Reticulócitos , Reticulócitos/patologia , Fatores de Risco , Ultrassonografia Doppler Transcraniana , Talassemia alfa/sangue , Talassemia alfa/patologia
13.
Nat Commun ; 6: 7870, 2015 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-26216346

RESUMO

The life-threatening Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive disorder. Twenty percent of patients cannot be explained by mutations in the known ICF genes DNA methyltransferase 3B or zinc-finger and BTB domain containing 24. Here we report mutations in the cell division cycle associated 7 and the helicase, lymphoid-specific genes in 10 unexplained ICF cases. Our data highlight the genetic heterogeneity of ICF syndrome; however, they provide evidence that all genes act in common or converging pathways leading to the ICF phenotype.


Assuntos
DNA Helicases/genética , Face/anormalidades , Síndromes de Imunodeficiência/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Mutação , Mutação de Sentido Incorreto , Doenças da Imunodeficiência Primária , Adulto Jovem
14.
Ther Drug Monit ; 36(6): 724-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24739665

RESUMO

BACKGROUND: Previous reports have suggested that imatinib may increase cyclosporine exposure by CYP3A4 inhibition. However, the magnitude of this drug interaction remains unclear. At present, quantitative information about the interaction profile of imatinib is scarce. METHODS: The authors report the effect of imatinib on cyclosporine exposure in 6 pediatric patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who received cyclosporine after hematopoietic stem-cell transplantation. Dose-normalized cyclosporine trough blood concentrations (TBC) were obtained before and after imatinib introduction. In addition, a validated model-based approach was used to derive quantitative predictions of CYP3A4-mediated drug interactions with imatinib as a victim or precipitant drug. RESULTS: The mean dose-normalized cyclosporine TBC significantly increased after 3 to 7 days of imatinib therapy. The modeling approach predicted weak-to-moderate effect of major CYP3A4 inhibitors on imatinib exposure. However, the inhibitory potency of imatinib was found to be similar to that of verapamil, suggesting significant influence of imatinib on the pharmacokinetics of drugs highly metabolized by CYP3A4. Observed increases in cyclosporine dose-normalized TBC of the 6 patients were compatible with model predictions. The observations and predictions suggest that imatinib may substantially increase cyclosporine exposure. CONCLUSIONS: Cyclosporine dose reduction may be necessary to avoid excessive immunosuppressive effect in case of coadministration of imatinib.


Assuntos
Benzamidas/farmacocinética , Transplante de Medula Óssea , Ciclosporina/farmacocinética , Imunossupressores/farmacocinética , Modelos Biológicos , Piperazinas/farmacocinética , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/farmacocinética , Adolescente , Benzamidas/sangue , Transplante de Medula Óssea/efeitos adversos , Criança , Ciclosporina/sangue , Interações Medicamentosas/fisiologia , Feminino , Humanos , Mesilato de Imatinib , Imunossupressores/sangue , Masculino , Piperazinas/sangue , Inibidores de Proteínas Quinases/sangue , Pirimidinas/sangue , Adulto Jovem
15.
J Pediatr ; 162(2): 423-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23092526

RESUMO

Erythrocytapheresis procedures, increasingly used in the management of patients with severe complications of sickle cell disease, are limited by adequate venous access. We have successfully used short-term femoral catheter insertion, during a 6.5-year period for a total of 443 procedures, to perform long-term erythrocytapheresis in 18 consecutive children with sickle cell disease.


Assuntos
Anemia Falciforme/terapia , Cateterismo Periférico , Citaferese , Eritrócitos , Adolescente , Cateterismo Periférico/métodos , Criança , Pré-Escolar , Veia Femoral , Humanos , Fatores de Tempo
16.
J Allergy Clin Immunol ; 129(3): 770-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22153772

RESUMO

BACKGROUND: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]). OBJECTIVE: This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome. METHODS: A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured. RESULTS: When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections. CONCLUSIONS: IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.


Assuntos
Agamaglobulinemia/imunologia , Anticorpos Antivirais/metabolismo , Infecções por Haemophilus/imunologia , Haemophilus influenzae/imunologia , Síndrome de Imunodeficiência com Hiper-IgM/imunologia , Imunoglobulina M/metabolismo , Adolescente , Agamaglobulinemia/complicações , Agamaglobulinemia/epidemiologia , Anticorpos Antivirais/imunologia , Criança , Feminino , Infecções por Haemophilus/complicações , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae/patogenicidade , Humanos , Síndrome de Imunodeficiência com Hiper-IgM/complicações , Síndrome de Imunodeficiência com Hiper-IgM/epidemiologia , Imunoglobulina M/imunologia , Incidência , Masculino , Estudos Prospectivos , Sistema Respiratório/imunologia , Sistema Respiratório/patologia , Sistema Respiratório/virologia , Risco
17.
BMC Cancer ; 9: 21, 2009 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-19146666

RESUMO

BACKGROUND: Lumbar punctures (LPs) are common in children with cancer. Although pain management during the lumbar puncture has been well standardized, dealing with stress and anxiety is not well addressed yet. Our objective was to evaluate the potential improvement of the LP success rate using a positioning pillow, to ensure maximum lumbar flexion, and allow paravertebral muscles to relax, in children who are awake, with either conscious sedation or no sedation. METHODS: Children aged 2-18 years undergoing LP were randomly assigned to a positioning pillow or no intervention. The primary outcome was the rate of success, i.e. achieving the LP (sampling or injection) at the first attempt, without bleeding (RBC < 50/mm3). The secondary outcomes included: the child's pain, assessed by a self-administered visual analogical scales (VAS) for children over 6 years of age; the parents' and caregivers' perception of the child's pain; the satisfaction of the children, the parents, the caregivers and the physician. The child's cooperation and the occurrence of post-LP syndrome were also evaluated. RESULTS: 124 children (62 in each group) were included. The LP pillow tended to increase the success rate of LPs (67% vs. 57%, p = 0.23), and decreased the post-LP syndromes (15% vs. 24%, p = 0.17) but the differences were not statistically significant. In children over 6-year of age (n = 72), the rate of success was significantly higher in the pillow group (58.5% vs. 41.5%, p = 0.031), with a tendency to feel less pain (median VAS 25 vs. 15 mm, p = 0.39) and being more satisfied (84.4% vs. 75.0%, p = 0.34). CONCLUSION: Overall results do not demonstrate a benefit in using this pillow for lumbar punctures. This study results also suggest a benefit in the sub group of children over 6-year of age; this result needs confirmation.


Assuntos
Neoplasias Hematológicas/diagnóstico , Postura , Punção Espinal/instrumentação , Punção Espinal/métodos , Adolescente , Fatores Etários , Ansiedade/etiologia , Ansiedade/prevenção & controle , Cuidadores , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Cefaleia/etiologia , Cefaleia/prevenção & controle , Humanos , Masculino , Dor/etiologia , Dor/prevenção & controle , Medição da Dor , Pais , Satisfação do Paciente , Punção Espinal/efeitos adversos
18.
J Pediatr Hematol Oncol ; 30(12): 928-30, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19131783

RESUMO

Although delayed hemolytic transfusion reaction (DHTR) has been widely recognized as a serious complication of red blood cell transfusion in patients with sickle cell disease (SCD), there is no consensus on its optimal management. Discontinuation of transfusion is recommended, whereas corticosteroids and immunoglobulins are considered to be beneficial. We report 2 children with sickle cell anemia who were diagnosed with DHTR and experienced a subsequent neurologic event in the course of treatment with corticosteroids. The role of corticosteroids as possible precipitating factors of neurologic complications is discussed. Pending a better understanding of the chain of events of DHTR, SCD children with DHTR should receive steroids with great caution.


Assuntos
Anemia Hemolítica/etiologia , Anemia Falciforme/terapia , Encefalopatias/induzido quimicamente , Transfusão de Eritrócitos/efeitos adversos , Glucocorticoides/efeitos adversos , Prednisolona/efeitos adversos , Adolescente , Anemia Hemolítica/tratamento farmacológico , Anemia Falciforme/sangue , Encefalopatias/diagnóstico , Criança , Feminino , Hemoglobinúria/etiologia , Hemólise , Humanos , Imunoglobulinas/análise , Imagem por Ressonância Magnética
19.
J Pediatr Hematol Oncol ; 30(12): 972-5, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19131795

RESUMO

Short-term intensive chemotherapy regimens have substantially improved the prognosis of pediatric patients with Burkitt lymphoma (BL), which now has an excellent overall outcome. However, central nervous system (CNS) involvement at diagnosis remains a poor prognostic factor, and progressive or relapsed disease in the CNS is associated with even worse outcomes. We report 3 boys aged 4, 7, and 12 years treated under the French Société Française d'Oncologie Pédiatrique LMB 89/96 protocols who presented, respectively, with CNS-/bone marrow+ stage-IV BL; CNS+ stage-IV BL; and stage-I BL. Each experienced an isolated CNS relapse, which was treated with CNS-directed salvage chemotherapy. All 3 are alive after 11 years of median follow-up, indicating that this chemotherapy regimen can be curative in pediatric BL with isolated CNS relapse.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Linfoma de Burkitt/patologia , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Humanos , Imagem por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia/patologia , Indução de Remissão , Resultado do Tratamento
20.
Eur J Cancer Prev ; 14(6): 531-40, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16284498

RESUMO

Metabolic polymorphisms may influence the risk of childhood leukaemia related to maternal tobacco, coffee or alcohol consumption. The data were extracted from a case-control study including 280 cases of acute leukaemia and 288 controls. Blood sampling was obtained for a representative subset of 219 cases and 105 controls. Gene-environment interactions were estimated using both case-control and case-only analyses. The polymorphisms of CYP1A1, GSTM1, GSTP1, GSTT1 and NQO1 were not associated with the risk of leukaemia. The slow EPHX1 allele was negatively associated with childhood leukaemia while an inverse non-significant association was observed with the fast EPHX1 allele. Maternal smoking during pregnancy was not related to leukaemia, but an interaction was observed in the case-only analysis with CYP1A1*2A variant allele (odds ratio (OR) 2.2 [1.0-4.9]) and with GSTM1 deletion (OR 2.3 [1.2-4.4]). Conversely, coffee drinking interacted negatively with NQO1 polymorphism in the case-only analysis (OR 0.6 [0.3-1.2] and 0.4 [0.1-1.0] for light and heavy coffee consumptions, respectively). This study suggests that maternal smoking may be a risk factor for leukaemia in children who carry CYP1A1 or GSTM1 genotypes, which might increase reactive metabolites of polycyclic aromatic hydrocarbons.


Assuntos
Citocromo P-450 CYP1A1/genética , Glutationa Transferase/genética , Leucemia/etiologia , Leucemia/genética , Efeitos Tardios da Exposição Pré-Natal , Doença Aguda , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Café , Feminino , Humanos , Razão de Chances , Polimorfismo Genético , Gravidez , Fatores de Risco , Fumar/efeitos adversos
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