Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
1.
Br J Haematol ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31309545

RESUMO

Autoimmune lymphoproliferative syndrome (ALPS) is a congenital disorder that results in an apoptosis impairment of lymphocytes, leading to chronic lymphoproliferation and autoimmunity, mainly autoimmune cytopenias. FAS gene defects are often responsible for the disease, the phenotype of which can vary from asymptomatic/mild forms to severe disease. More rarely, defects are associated to  other genes involved in apoptosis pathway, such as CASP10. Few data are available on CASP10-mutated patients. To date, two CASP10 mutations have been recognized as pathogenic (I406L and L258F) and others have been reported with controversial result on their pathogenicity (V410l, Y446C) or are known to be polymorphic variants (L522l). In this study, we evaluated apoptosis function in patients with an ALPS/ALPS-like phenotype carrying CASP10 variants. Molecular findings were obtained by next generation sequencing analysis of genes involved in immune dysregulation syndromes. Functional studies were performed after inducing apoptosis by FAS-ligand/TRIAL stimulation and analysing cell death and the function of CASP10, CASP8 and PARP proteins. We identified 6 patients with an ALPS (n = 2) or ALPS-like (n = 4) phenotype, carrying I406L (n = 1),V410l (n = 2),Y446C (n = 1) heterozygous CASP10 variants or the L522l polymorphisms (n = 2) associated with another polymorphic homozygote variant on CASP8 or a compound heterozygous mutation on TNFRSF13C. Apoptosis was impaired in all patients showing that such variants may play a role in the development of clinical phenotype.

2.
Am J Hematol ; 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30456824

RESUMO

Autoimmune neutropenia of infancy (AIN) is characterized by low risk of severe infection, tendency to spontaneously resolve and typically onset at < 4-5 years of age; it is due to auto-antibodies whose detection is often difficult. In case of negativity of 4 anti-neutrophils autoantibody tests, after having excluded ethnic, post infection, drug induced or congenital neutropenia, according to the Italian guidelines the patients will be defined as affected by "idiopathic neutropenia" (IN). We describe the characteristics of 85 IN patients enrolled in the Italian neutropenia registry: they were compared to 336 children affected by AIN. The two groups were clinically very similar and the main differences were detection age (later in IN), length of disease (longer in IN) and, among recovered patients, age of spontaneous recovery: the median age at resolution was 2.13 years in AINs and 3.03 years in INs (p = 0.00002). At bivariate analysis among AIN patients earlier detection age (p = 0.00013), male sex (p = 0.000748), absence of leucopenia (p = 0.0045), and absence of monocytosis (p = 0.0419) were significantly associated with earlier recovery; in the IN group only detection age (p = 0.013) and absence of monocytosis (p = 0.0333) were significant. At multivariate analysis detection age and absence of monocytosis were independently significant (p = 6.7e-05 and p = 4.4e-03 respectively) in the AIN group, whereas in the IN group only detection age stayed significant (p = 0.013). This article is protected by copyright. All rights reserved.

3.
Br J Haematol ; 183(1): 110-118, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29984823

RESUMO

Dyskeratosis congenita (DC) is a genetic multisystem disorder with frequent involvement of the bone marrow. Haematopoietic stem cell transplantation (HSCT) is the only definitive cure to restore haematopoiesis, even though it cannot correct other organ dysfunctions. We collected data on the outcome of HSCT in the largest cohort of DC (n = 94) patients ever studied. Overall survival (OS) and event-free survival (EFS) at 3 years after HSCT were 66% and 62%, respectively. Multivariate analysis showed better outcomes in patients aged less than 20 years and in patients transplanted from a matched, rather than a mismatched, donor. OS and EFS curves tended to decline over time. Early lethal events were infections, whereas organ damage and secondary malignancies appeared afterwards, even a decade after HSCT. A non-myeloablative conditioning regimen appeared to be most advisable. Organ impairment present before HSCT seemed to favour the development of chronic graft-versus-host disease and T-B immune deficiency appeared to enhance pulmonary fibrosis. According to the present data, HSCT in DC is indicated in cases of progressive marrow failure, whereas in patients with pre-existing organ damage, this should be carefully evaluated. Further efforts to investigate treatment alternatives to HSCT should be encouraged.

7.
Mycoses ; 60(12): 789-795, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28833726

RESUMO

Plasma 1,3-ß-D-glucan (BDG) is indicated as a tool for early diagnosis of invasive fungal diseases (IFD). However, data on its diagnostic value are scarce in children. Therefore, definition of BDG test performance in paediatrics is needed. BDG was evaluated in children admitted to "Istituto Giannina Gaslini," Genoa, Italy, who developed clinical conditions at risk for IFD. Results were analysed for sensitivity, specificity, predictive values, likelihood ratios, accuracy, informedness and probability of missing one case by a negative test. A total of 1577 BDG determinations were performed on 255 patients (49% males, median age 5.4 years). Overall 46 IFD were diagnosed, 72% proven/probable. The test performance was evaluated for 80 pg/mL, 120 pg/mL, 200 pg/mL, 350 pg/mL, 400 pg/mL cut offs. Sensitivity was always <0.80 and specificity > 0.90 only for cut offs ≥200 pg/mL. Negative predictive value was ≥0.90 for all the cut offs evaluated, while positive predictive value resulted barely 0.50 (8% IFD prevalence). Accuracy was never >0.90, and informedness was at best 0.50. The risk of missing one IFD by a negative result was < 10%. Analyses in haemato-oncological or newborn patients did not show major differences. Detection of serum BDG does not appear a valuable adjunctive diagnostic tool for IFD in paediatrics.


Assuntos
Técnicas e Procedimentos Diagnósticos , Infecções Fúngicas Invasivas/diagnóstico , beta-Glucanas/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Infecções Fúngicas Invasivas/sangue , Infecções Fúngicas Invasivas/microbiologia , Itália , Masculino , Curva ROC , Sensibilidade e Especificidade
9.
Mycoses ; 60(2): 118-123, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27681940

RESUMO

To describe the epidemiology of invasive Candida infection in a tertiary care paediatric hospital. Prospective single-centre survey on all Candida strains isolated from normally sterile fluids and urines in the period 2005-2015 . A total of 299 ICI were documented in 262 patients. Urinary tract infection represented the most frequent diagnosis (62%), followed by fungaemia (34%) and peritonitis (4%). Fungaemia was most frequent in children with cancer (59%) or in low birth weight neonates (61%), while urinary tract infections were more frequent in patients with urinary tract malformation. C.albicans was the most frequently isolated species (60%) compared with C. non-albicans, but differences were present according to the site of isolation and underlying conditions. Overall 90-day mortality was 7%, 13% in fungaemias, 8% in peritonitis and 2% in urinary tract infections. The rates of invasive Candida infection increased during the study period. Invasive Candida infection is diagnosed with increasing frequency in children. Site of isolation and aetiology are frequently related with the presence of underlying, favouring conditions. Mortality was not negligible, especially in the presence of more invasive infections and specific underlying conditions.


Assuntos
Candida/isolamento & purificação , Candidíase Invasiva/epidemiologia , Candidíase Invasiva/microbiologia , Candidíase/epidemiologia , Adolescente , Antifúngicos/uso terapêutico , Candida albicans/isolamento & purificação , Candidíase/microbiologia , Candidíase/mortalidade , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/mortalidade , Criança , Feminino , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Fungemia/microbiologia , Fungemia/mortalidade , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Neoplasias/complicações , Neoplasias/microbiologia , Peritonite/tratamento farmacológico , Peritonite/epidemiologia , Peritonite/microbiologia , Peritonite/mortalidade , Estudos Prospectivos , Fatores de Risco , Centros de Atenção Terciária , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Infecções Urinárias/mortalidade
12.
Br J Haematol ; 175(3): 490-495, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27447678

RESUMO

Mycophenolate mofetil (MMF) has been shown to be effective in children with immune thrombocytopenia (ITP) and Evans syndrome (ES), but data from larger series and details on the timing of the response are lacking. We evaluated 56 children treated with MMF for ITP (n = 40) or ES (n = 16), which was primary or secondary to autoimmune lymphoproliferative syndrome -related syndrome (ARS). Thirty-five of the 54 evaluable patients (65%) achieved a partial (18%) or complete (46%) response after a median (range) of 20 (7-137) and 37 (7-192) d, respectively. ITP and ES patients responded in 58% and 81% of cases (P = not significant, ns), with complete response in 32% and 81% (P = 0·01), respectively. 60% and 73% of children with primary disease and ARS responded (P = ns) with complete response in 34% and 68% of cases (P = 0·01), respectively. Six of 35 (17%) children relapsed after a median of 283 d (range 189-1036). Limited toxicity was observed in four patients. The median durations of treatment and follow-up were seven and 12·7 months, respectively. This is the largest reported cohort of patients treated with MMF for ITP/ES. The results show that MMF is effective and safe and provides a relatively quick response, suggesting that it has a potential role as an alternative to more aggressive and expensive second/further-line treatments.


Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Antibióticos Antineoplásicos/uso terapêutico , Ácido Micofenólico/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Trombocitopenia/tratamento farmacológico , Adolescente , Anemia Hemolítica Autoimune/diagnóstico , Antibióticos Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Itália , Masculino , Ácido Micofenólico/efeitos adversos , Razão de Chances , Púrpura Trombocitopênica Idiopática/diagnóstico , Recidiva , Retratamento , Estudos Retrospectivos , Trombocitopenia/diagnóstico , Resultado do Tratamento
13.
JIMD Rep ; 26: 37-43, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26238250

RESUMO

Pearson syndrome (PS) is a very rare and often fatal multisystemic mitochondrial disorder involving the liver, kidney, pancreas, and hematopoietic and central nervous system. It is characterized principally by a transfusion-dependent anemia that usually improves over time, a tendency to develop severe infections, and a high mortality rate. We describe a group of 11 PS patients diagnosed in Italy in the period 1993-2014. The analysis of this reasonably sized cohort of patients contributes to the clinical profile of the disease and highlights a rough incidence of 1 case/million newborns. Furthermore, it seems that some biochemical parameters like increased serum alanine and urinary fumaric acid can help to address an early diagnosis.

15.
Blood ; 126(16): 1885-92; quiz 1970, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26185129

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day +90) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken.


Assuntos
Ciclosporina/administração & dosagem , Rejeição de Enxerto , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Metotrexato/administração & dosagem , Neutropenia , Doadores não Relacionados , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Humanos , Incidência , Masculino , Oriente Médio , Neutropenia/congênito , Neutropenia/epidemiologia , Neutropenia/terapia , Estudos Retrospectivos , Sociedades Médicas
16.
Br J Haematol ; 171(2): 247-253, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26058843

RESUMO

The management of refractory autoimmune cytopenias in childhood is challenging due to the lack of established evidence on escalating treatments. The long-term efficacy of immunosuppressive drugs was evaluated in children with refractory autoimmune cytopenias referred to the Haematology Unit of the Gaslini Children's Hospital between 2001 and 2014. Patients were grouped into three categories: autoimmune lymphoproliferative syndrome (ALPS), ALPS-related syndrome (at least one absolute/primary additional criterion for ALPS) and primary autoimmune cytopenia (PAC, cytopenia with no other immunological symptoms/signs). Fifty-eight children (aged 1-16 years) entered the study: 12 were categorized with ALPS, 24 were ALPS-related and 22 had PAC. Five didn't receive treatment. Fifty-three were initially treated with steroids/intravenous immunoglobulin. Fourteen responded, whereas 39 did not. Of these 39 patients, 34 (87%) received mycophenolate mofetil (MMF) as second/further-line treatment and 22 (65%) responded. Within these 34 subjects, ALPS patients responded better (11/11, 100%) than the two other groups pooled together (11/23, 48%; P = 0·002). Sirolimus was given as second/further-line treatment to 16 children, and 12 (75%) responded, including 8 who previously failed MMF therapy. Median follow-up was 3·46 years. MMF and Sirolimus were well-tolerated and enabled partial/complete and sustained remission in most children. These drugs may be successfully and safely used in children with refractory autoimmune cytopenias with or without ALPS/ALPS-related disorders and may represent a valid second/further line option.

17.
Blood Cells Mol Dis ; 55(1): 40-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25976466

RESUMO

Acquired aplastic anemia (AA) is a rare heterogeneous disease characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3/million inhabitants/year, in Europe, but higher in East Asia. Survival in severe aplastic anemia (SAA) has markedly improved in the past 2 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive and biologic drugs, and supportive care. In SAA hematopoietic stem cell transplant (HSCT) from a matched sibling donor (MSD) is the treatment of choice. If a MSD is not available, the options include immunosuppressive therapy (IST) or unrelated donor HSCT. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary, evidence-based document issued by a group of pediatric hematologists was discussed, modified and approved during a series of "Consensus Conferences" according to procedures previously validated by the AIEOP Board. The guidelines highlight the importance of referring pediatric patients with AA to pediatric centers with long experience in diagnosis, differential diagnosis, management, supportive care and follow-up of AA.


Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Pancitopenia/diagnóstico , Pancitopenia/terapia , Anemia Aplástica/induzido quimicamente , Anemia Aplástica/imunologia , Antibacterianos/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Soro Antilinfocitário/uso terapêutico , Antirreumáticos/efeitos adversos , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/patologia , Criança , Ciclosporina/uso terapêutico , Gerenciamento Clínico , Teste de Histocompatibilidade , Humanos , Organofosfatos/toxicidade , Pancitopenia/induzido quimicamente , Pancitopenia/imunologia , Irmãos , Doadores não Relacionados
20.
Biomed Res Int ; 2014: 707691, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24868544

RESUMO

OBJECTIVE: Vaccinations are the most important tool to prevent infectious diseases. Chemotherapy-induced immune depression may impact the efficacy of vaccinations in children. PATIENTS AND METHODS: A panel of experts of the supportive care working group of the Italian Association Paediatric Haematology Oncology (AIEOP) addressed this issue by guidelines on vaccinations in paediatric cancer patients. The literature published between 1980 and 2013 was reviewed. RESULTS AND CONCLUSION: During intensive chemotherapy, vaccination turned out to be effective for hepatitis A and B, whilst vaccinations with toxoid, protein subunits, or bacterial antigens should be postponed to the less intensive phases, to achieve an adequate immune response. Apart from varicella, the administration of live-attenuated-virus vaccines is not recommended during this phase. Family members should remain on recommended vaccination schedules, including toxoid, inactivated vaccine (also poliomyelitis), and live-attenuated vaccines (varicella, measles, mumps, and rubella). By the time of completion of chemotherapy, insufficient serum antibody levels for vaccine-preventable diseases have been reported, while immunological memory appears to be preserved. Once immunological recovery is completed, usually after 6 months, response to booster or vaccination is generally good and allows patients to be protected and also to contribute to herd immunity.


Assuntos
Antineoplásicos/uso terapêutico , Hematologia/normas , Oncologia/normas , Pediatria/normas , Guias de Prática Clínica como Assunto , Vacinação/normas , Adolescente , Criança , Vacinas contra Hepatite A/uso terapêutico , Vacinas contra Hepatite B/uso terapêutico , Humanos , Sistema Imunitário , Imunidade Coletiva , Programas de Imunização , Vacinação/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA