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1.
Bone Marrow Transplant ; 55(1): 126-136, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31455899

RESUMO

Information on incidence, and factors associated with mortality is a prerequisite to improve outcome after hematopoietic stem cell transplantation (HSCT). Therefore, 55'668 deaths in 114'491 patients with HSCT (83.7% allogeneic) for leukemia were investigated in a landmark analysis for causes of death at day 30 (very early), day 100 (early), at 1 year (intermediate) and at 5 years (late). Mortality from all causes decreased from cohort 1 (1980-2001) to cohort 2 (2002-2015) in all post-transplant phases after autologous HSCT. After allogeneic HSCT, mortality from infections, GVHD, and toxicity decreased up to 1 year, increased at 5 years; deaths from relapse increased in all post-transplant phases. Infections of unknown origin were the main cause of infectious deaths. Lethal bacterial and fungal infections decreased from cohort 1 to cohort 2, not unknown or mixed infections. Infectious deaths were associated with patient-, disease-, donor type, stem cell source, center, and country- related factors. Their impact varied over the post-transplant phases. Transplant centres have successfully managed to reduce death after HSCT in the early and intermediate post-transplant phases, and have identified risk factors. Late post-transplant care could be improved by focus on groups at risk and better identification of infections of "unknown origin".

3.
Artigo em Inglês | MEDLINE | ID: mdl-31844137

RESUMO

In the absence of an HLA-matched donor, the best treatment for acquired aplastic anemia patients refractory to immunosuppression is unclear. We collected and analyzed data from all acquired aplastic anemia patients who underwent a haploidentical transplantation with posttransplant cyclophosphamide in Europe from 2011 to 2017 (n = 33). The cumulative incidence of neutrophil engraftment was 67% (CI95%: 51-83%) at D +28 and was unaffected by age group, stem cell source, ATG use, or Baltimore conditioning regimen. The cumulative incidence of grades II-III acute GvHD was 23% at D +100, and limited chronic GvHD was 10% (0-20) at 2 years, without cases of grade IV acute or extensive chronic GvHD. Two-year overall survival was 78% (64-93), and 2-year graft-versus-host disease-free survival was 63% (46-81). In univariate analysis, the 2-year OS was higher among patients who received the Baltimore conditioning regimen (93% (81-100) versus 64% (41-87), p = 0.03), whereas age group, stem cell source, and ATG use had no effect. Our results using unmanipulated haploidentical transplantation and posttransplant cyclophosphamide for treating refractory AA patients are encouraging, but warrant confirmation in a prospective study with a larger number of patients and longer follow-up.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31876783

RESUMO

In recent years, monogenic causes of immune dysregulation syndromes, with variable phenotypes, have been documented. Mutations in the lipopolysaccharide-responsive beige-like anchor (LRBA) protein are associated with common variable immunodeficiency, autoimmunity, chronic enteropathy, and immune dysregulation disorders. The LRBA protein prevents degradation of cytotoxic T-lymphocyte antigen 4 (CTLA4) protein, thus inhibiting immune responses. Both LRBA and CTLA4 deficiencies usually present with immune dysregulation, mostly characterized by autoimmunity and lymphoproliferation. In this report, we describe a patient with an atypical clinical onset of LRBA deficiency and the patient's response to abatacept, a fusion protein-drug that mimics the action of CTLA4.

5.
Blood ; 134(Supplement_1): 44, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31724018

RESUMO

DISCLOSURES: Bader: Riemser, Neovii: Research Funding; Medac: Patents & Royalties, Research Funding; Amgen (Brasil), Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy. Risitano:Alexion: Honoraria, Research Funding, Speakers Bureau; Achillion: Research Funding; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biocryst: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Research Funding, Speakers Bureau; Amyndas: Consultancy; Samsung: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amyndas: Consultancy; Biocryst: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ra Pharma: Research Funding; Ra Pharma: Research Funding; Alnylam: Research Funding; Alnylam: Research Funding; Achillion: Research Funding. Peffault de Latour:Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding.

6.
Haematologica ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582549

RESUMO

This follow-up study of the randomized prospective trial included 192 patients with newly diagnosed severe aplastic anemia receiving Antithymoglobulin and Cyclosporine, with and without G-CSF. We aimed to evaluate the long-term effect of G-CSF on overall survival, event-free survival, probability of secondary myelodysplastic syndrome or acute myeloid leukemia, clinical paroxysmal nocturnal hemoglobinuria, relapse, avascular osteonecrosis and chronic kidney disease. The median follow-up was 11.7 years (10.9-12.5). Overall survival at 15 years was 57±12% for the G-CSF and 63±12% for the non-G-CSF group (P=0.92), event-free survival 24±10% for the G-CSF, and 23±10% for the non-G-CSF group (P=0.36). In total, 9 patients developed myelodysplastic syndrome or acute myeloid leukemia, and 10 clonal cytogenetic abnormality only, 7 solid cancer, 18 clinical paroxysmal nocturnal hemoglobinuria, 8 osteonecrosis, and 12 chronic kidney disease, without any difference between patients treated with or without G-CSF. Cumulative incidence at 15 years of myelodysplastic syndrome, acute myeloid leukemia or isolated cytogenetic abnormality was 8.5±3% for the G-CSF, and 8.2±3% for the non-G-CSF group (P=0.90). Cumulative incidence of any late event including myelodysplastic syndrome or acute myeloid leukemia , isolated cytogenetic abnormalities, solid cancer, clinical paroxysmal nocturnal hemoglobinuria, aseptic osteonecrosis, chronic kidney disease and relapse was 50±12% for the G-CSF, and 49±12% for the non-G-CSF group (P=0.65). Our results demonstrate that it is unlikely that G-CSF impacts on the outcome of severe aplastic anemia; nevertheless, very late events are common and eventually impact on the prognosis of these patients, irrespectively of their age at immunosuppressive therapy (NCT01163942).

7.
Artigo em Inglês | MEDLINE | ID: mdl-31554929

RESUMO

This retrospective study explored the incidence of autoimmune cytopenia (AIC) in 530 paediatric and adult patients with acquired aplastic anaemia (aAA) who underwent first allogeneic HSCT between 2002 and 2012. AIC was a rare complication with a cumulative incidence of AIC at 1, 3, 5 and 10 years post HSCT of 2.5% (1.2-3.9 95% CI), 4.4% (2.6-6.2 95% CI), 4.6% (2.8-6.5 95% CI) and 5.1% (3.1-7.2 95% CI). Overall survival at 5 years after diagnosis of AIC was 85.9% (71-100 95% CI). Twenty-five patients were diagnosed with AIC at a median of 10.6 (2.6-91.5) months post HSCT. Eight (32%) patients were diagnosed with immune thrombocytopenia (ITP), seven (28%) with autoimmune haemolytic anaemia (AIHA), seven (24%) with Evans syndrome and four (16%) with autoimmune neutropenia (AIN). Treatment strategies were heterogeneous. Complete responses were seen in 12 of 25 patients, with death in three patients. In multivariable Cox analysis of a subgroup of 475 patients, peripheral blood stem cell (PBSC) transplant was associated with higher risk of AIC compared with bone marrow (BM) when conditioning regimens contained fludarabine and/or alemtuzumab (2.81 [1.06-7.49 95% CI]; p = 0.038), or anti-thymocyte globulin (ATG) (2.86 [1.11-7.37 95% CI]; p = 0.029). Myeloablative conditioning was associated with a lower risk of AIC compared with reduced intensity conditioning (RIC) in fludarabine and/or alemtuzumab (0.34 [0.12-0.98 95% CI]; p = 0.046) and ATG containing regimens (0.34 [0.12-0.95 95% CI]; p = 0.04). These findings provide clinically useful information regarding the incidence of a rare and potentially life-threatening complication of allogeneic HSCT for aAA, and further support for BM as the preferred stem cell source for transplant of patients with aAA.

8.
Blood ; 134(23): 2036-2045, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31511239

RESUMO

Chronic myeloid leukemia (CML) is rare in children and accounts for ≤15% of all myeloid leukemia cases. When we initiated this study with nilotinib, imatinib was the only tyrosine kinase inhibitor indicated for pediatric patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance or intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph+ CML-CP R/I to imatinib or dasatinib or newly diagnosed Ph+ CML-CP. Data presented are from analyses with minimum follow-up of up to 24 cycles (1 cycle is 28 days). Fifty-nine patients with Ph+ CML-CP were enrolled, and 58 were treated (R/I, n = 33; newly diagnosed, n = 25). Major molecular response (MMR) rate at cycle 6 in the R/I cohort was 39.4% (primary end point); 57.6% of patients achieved or maintained MMR and 81.8% achieved or maintained complete cytogenetic response (CCyR) by 24 cycles. In patients with newly diagnosed disease, rates of MMR by cycle 12 and CCyR at cycle 12 were 64.0% each (primary end points); by cycle 24, cumulative MMR and CCyR rates were 68.0% and 84.0%, respectively. The safety profile of nilotinib in pediatric patients was generally comparable with the known safety profile in adults, although cardiovascular events were not observed in this study, and hepatic laboratory abnormalities were more frequent; no new safety signals were identified. In summary, nilotinib demonstrated efficacy and a manageable safety profile in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01844765.

9.
Lancet Haematol ; 6(11): e573-e584, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31477550

RESUMO

BACKGROUND: The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. METHODS: In this retrospective, multicentre study, we assessed the outcomes for adult patients (≥18 years) with haematological malignancies who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) between Jan 3, 2001, and Dec 31, 2015, and were reported to the European Society for Blood and Marrow Transplantation. The donor types studied were matched sibling, matched unrelated, mismatched unrelated, haploidentical, and cord blood donors. Unrelated non-cord-blood donors and recipients were typed at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1. We evaluated trends in overall survival, non-relapse mortality, relapse incidence, progression-free survival, acute and chronic graft-versus-host disease (GVHD), and GVHD-free and relapse-free survival following transplantation from various donor types (matched sibling, matched unrelated, mismatched unrelated, haploidentical, and umbilical cord blood), and compared transplantation outcomes across three epochs (epoch 1: 2001-05; epoch 2: 2006-10; and epoch 3: 2011-15). We used Kaplan-Meier estimators for survival probabilities and cumulative incidence functions accounting for competing risks for probabilities of GHVD, relapse, and non-relapse mortality, using multiple imputations by chained equations to deal with missing data. In epoch 3, we directly compared outcomes by donor group, stratified by a novel three-level disease-risk scheme. FINDINGS: We included 106 188 patients in our analysis. The median follow-up was 4·1 years (IQR 1·7-7·7). Overall survival at 3 years increased with all donor groups between epochs 2 and 3 (matched sibling: 54·0% [95% CI 53·1-54·8] to 54·6% [53·6-55·6]; matched unrelated: 49·1% [48·0-50·2] to 51·6% [50·7-52·6]; mismatched unrelated: 37·4% [35·7-39·2] to 41·3% [39·5-43·1]; haploidentical: 34·5% [31·4-37·9] to 44·2% [42·1-46·3]; and cord blood 36·3% [33·9-39] to 43·7% [40·8-46·8]). Improvement in overall survival seems to be driven by a reduction in non-relapse mortality, except in cord blood HSCT recipients, who had a lower relapse incidence. Comparing donor groups across disease-risk strata using the novel disease-risk scheme, overall survival among recipients of matched sibling transplantations remained better than other donor groups except in high-risk disease, where overall survival with matched unrelated transplantations was not different. INTERPRETATION: Overall survival following allogeneic stem cell transplantation is improving with substantial progress among recipients of haploidentical and cord blood HSCT. Nonetheless, the traditional donor hierarchy of matched sibling donors followed by matched unrelated donors and then other donors holds. Our findings warrant further investigation and could inform decision making and the development of donor-selection algorithms. FUNDING: The Varda and Boaz Dotan Research Center in Haemato-Oncology, Tel Aviv University, and the Shalvi Foundation for Research.


Assuntos
Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/mortalidade , Doenças Hematológicas/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Recidiva , Sistema de Registros , Estudos Retrospectivos , Sociedades Médicas , Transplante Homólogo
11.
Br J Haematol ; 187(4): 502-508, 2019 Nov.
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.

12.
Expert Rev Hematol ; 12(10): 809-819, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31311355

RESUMO

Introduction: About 60% of aplastic anemia (AA) patients are in need of further treatment after frontline standard immunosuppressive therapy (IST). This along with the prolonged survival of AA subjects who do not respond to or relapse after this treatment makes management of these patients a rising and very challenging issue. Areas covered: Literature research, carried out from the most commonly used databases, included the following keywords: aplastic anemia, immunosuppressive treatment, antithymocyte globuline, ciclosporine A, refractory aplastic anemia, relapsing aplastic anemia, hematopoietic stem cell transplantation including haploidentical and cord blood transplantations thrombopoietin mimetics, supportive treatment, chelation and infections. Studies on the treatment of aplastic anemia with different levels of evidence were included. Top level of evidence studies (metanalyses and randomized prospective controlled trials) were a minority because severe AA, particularly in the subset of patients who fail upfront IST, is an extremely rare disease. Guidelines from National Societies and review articles were also included. Expert opinion: The most commonly used treatments after failure of upfront immunosuppression are hematopoietic stem cell transplantation, a second course of immunosuppression and thrombopoietin mimetics alone or in combination with immunosuppression. Other potential options are alemtuzumab, androgens, oral cyclosporine A in monotherapy. Not many comparative studies exist to clearly establish the superiority of one over another strategy. Therefore, the choice of the best treatment for these patients should rely on major driving factors like patient's age and comorbidities, availability of a matched unrelated donor, donor's characteristics and drug-availability.

13.
Bone Marrow Transplant ; 54(10): 1525-1552, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30953028

RESUMO

This is the seventh special EBMT report on the indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on transplant indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered together with the risk of the disease, the risk of the transplant procedure and the results of non-transplant strategies. In over two decades since the first report, the EBMT indications manuscripts have incorporated changes in transplant practice coming from scientific and technical developments in the field. In this same period, the establishment of JACIE accreditation has promoted high quality and led to improved outcomes of patient and donor care and laboratory performance in transplantation and cellular therapy. An updated report with operating definitions, revised indications and an additional set of data with overall survival at 1 year and non-relapse mortality at day 100 after transplant in the commonest standard-of-care indications is presented. Additional efforts are currently underway to enable EBMT member centres to benchmark their risk-adapted outcomes as part of the Registry upgrade Project 2020 against national and/or international outcome data.

14.
Leuk Res ; 80: 19-25, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30908982

RESUMO

The bone marrow failure (BMF) syndromes are a group of rare disorders characterized by ineffective hematopoiesis resulting from deficiencies in the hematopoietic stem cell compartment. Although these diseases are typically acquired, some forms (e.g., Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia, and Shwachman Diamond syndrome) are inherited. Patients with BMF syndromes can develop peripheral blood cytopenias and pancytopenia, and their disease can ultimately progress to acute myelogenous leukemia (AML). Research around the world is shedding light on the biology of the BMF syndromes, their clinical effects, and novel treatments. The Aplastic Anemia and MDS International Foundation (AAMDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMF syndromes. This report summarizes presentations on the latest scientific discoveries in BMF syndromes from the Sixth International Bone Marrow Failure Disease Scientific Symposium sponsored by AAMDSIF on March 22-23, 2018, in Rockville, Maryland.

15.
Ann Hematol ; 98(6): 1341-1350, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915499

RESUMO

Eltrombopag (ELT), an oral thrombopoietin receptor agonist, has recently emerged as a promising new drug for the treatment of aplastic anemia (AA). How ELT is used outside of clinical trials in the real-world setting and results of this treatment are not known. We conducted therefore a retrospective survey on the use of ELT in AA among EBMT member centers. We analyzed the 134 patients reported in our survey together with 46 patients recently published by Lengline et al. The median follow-up from start of ELT treatment was 15.3 months, with 85.6% patients alive at last follow-up. Importantly, only 28.9% of our patients received ELT according to the FDA/EMA label as monotherapy in the relapsed/refractory setting, whereas 16.7% received ELT upfront. The overall response rate in our cohort was 62%, very similar to the results of the pivotal ELT trial. In multivariate analysis, combination therapy with ELT/cyclosporine/ATG and response to previous therapy were associated with response. Overall survival was favorable with a 1-year survival from ELT start of 87.4%. We identified age, AA severity before ELT start and response to ELT as variables significantly associated with OS. Two patients transformed to MDS; other adverse events were mostly benign. In sum, ELT is used widely in Europe to treat AA patients, mostly in the relapsed/refractory setting. Response to ELT is similar to the clinical trial data across different age groups, treatment lines, and treatment combinations and results in favorable survival.


Assuntos
Anemia Aplástica/tratamento farmacológico , Benzoatos/uso terapêutico , Hidrazinas/uso terapêutico , Pirazóis/uso terapêutico , Adulto , Idoso , Anemia Aplástica/mortalidade , Avaliação de Medicamentos , Uso de Medicamentos , Europa (Continente) , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/etiologia , Modelos de Riscos Proporcionais , Receptores de Trombopoetina/agonistas , Estudos Retrospectivos , Adulto Jovem
17.
Am J Hematol ; 94(1): 80-86, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30328134

RESUMO

We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti-thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14-0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35-0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas , Depleção Linfocítica , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Alemtuzumab/uso terapêutico , Anemia Aplástica/imunologia , Soro Antilinfocitário/uso terapêutico , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunização Passiva , Lactente , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do Tratamento , Adulto Jovem
18.
Am J Hematol ; 94(2): 216-222, 2019 02.
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 antineutrophils autoantibody tests, after having excluded ethnic, postinfection, 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 with 336 children affected by AIN. The 2 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 = .00002). At bivariate analysis among AIN patients earlier detection age (P = .00013), male sex (P = .000748), absence of leucopenia (P = .0045), and absence of monocytosis (P = .0419) were significantly associated with earlier recovery; in the IN group only detection age (P = .013) and absence of monocytosis (P = .0333) were significant. At multivariate analysis detection age and absence of monocytosis were independently significant (P = 6.7e-05 and 4.4e-03, respectively) in the AIN group, whereas in the IN group only detection age stayed significant (P = .013).


Assuntos
Neutropenia/congênito , Fatores Etários , Autoimunidade , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Itália , Leucopenia , Masculino , Neutropenia/diagnóstico , Neutropenia/epidemiologia , Sistema de Registros , Fatores de Risco , Fatores Sexuais
19.
Metab Syndr Relat Disord ; 17(1): 53-59, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30376422

RESUMO

PURPOSE: Fanconi anemia (FA) is a complex tumor-prone disease defined by an entangled genotype and phenotype. Despite enormous efforts in the last 20 years, a comprehensive and integrated view of the disease is still missing. The aim of this pilot study was to establish whether a global microRNA (miRNA) analysis approach could be helpful in defining aspects in FA phenotype, which might deserve future attention with the perspective to develop miRNA-based therapies. METHODS: miRNA array were employed to characterize the global miRNA (miRNoma) profile of FA RNA samples with respect to normal samples. RESULTS: We report and compare miRNA profile from two FA established cell lines and three FA patients. This analysis reveals that 36 and 64 miRNAs, respectively, are found differentially expressed (>2-fold variation and P < 0.05) in the samples from FA cell lines and FA patients. Overlap of these data results in 24 miRNAs as shared in the two sample populations. Available bioinformatics methods were used to predict target genes for the differentially expressed miRNAs and to perform pathway enrichment analysis. CONCLUSIONS: Seven pathway results associated with the FA phenotype. It is interesting to note that some of these pathways were previously unrelated to FA phenotype. It might be important to focus on these pathways not previously emerged as dysfunctional in FA to better define the pathophysiological context of this disease. This is the first report of a global miRNA analysis in FA.


Assuntos
Anemia de Fanconi/genética , MicroRNAs/genética , Transcriptoma , Estudos de Casos e Controles , Linhagem Celular , Criança , Anemia de Fanconi/epidemiologia , Feminino , Perfilação da Expressão Gênica , Genótipo , Humanos , Masculino , Análise em Microsséries , Fenótipo , Projetos Piloto
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