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CONTEXT.: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.
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Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.
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Linfohistiocitosis Hemofagocítica , Paniculitis , Niño , Preescolar , Humanos , Lactante , Mutación de Línea Germinal , Receptor 2 Celular del Virus de la Hepatitis A/genética , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/complicaciones , Paniculitis/tratamiento farmacológico , Paniculitis/genéticaRESUMEN
Ruxolitinib (RUX), a small molecule inhibitor of JAK1/JAK2, has been identified as the possible novel targeted agent for the treatment of hemophagocytic lymphohistiocytosis (HLH). However, due to the lack of randomized clinical trials (RCTs), it is extremely difficult to determine the effective therapeutic dose for RUX in HLH patients, especially in pediatric patients. At the same time, the clinical response of pediatric patients to RUX varies greatly among individuals according to several case reports. Therefore, it is imperative to investigate the pharmacokinetic and pharmacodynamic characteristics of RUX in HLH children, and this must be based on a satisfactory method to determine the concentration of RUX. Owing to several limits of published analytical methods, herein, we describe a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for monitoring RUX in children's plasma samples. The protein precipitation method using methanol was used for sample cleanup. The analytes were separated by gradient elution in which 2.0 mM ammonium acetate in distilled water and acetonitrile were used as mobile phases. In the positive electrospray ionization (ESI+) mode, the m/z 307.1 â 186.0 and 316.1 â 185.9 ion pair transitions of RUX and RUX-d9 were used for the qualitative and quantitative analysis, respectively. The calibration curves of RUX were linear in the concentration range from 0.5 to 400 ng mL-1. The intra- and inter-batch precision, accuracy, recovery, dilution completeness, and stability of this method were all within acceptable standards, and no matrix effects or residues were found. This method was successfully applied to the clinical pharmacokinetic study of RUX in 32 children with HLH. The pharmacokinetic parameters of HLH children after a single dose of RUX and the steady state plasma concentration after multiple administrations were proposed through this method. Most importantly, it was found that the age and serum creatinine (SCr) of children with HLH had a significant and complex impact on the in vivo process of RUX after the single as well as multiple administrations of RUX.
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Linfohistiocitosis Hemofagocítica , Espectrometría de Masas en Tándem , Niño , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Humanos , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Nitrilos , Pirazoles , Pirimidinas , Reproducibilidad de los Resultados , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder characterized by hyperinflammation. Recently, ruxolitinib (RUX), targeting key cytokines in HLH, has shown promise for HLH treatment. However, there is a lack of robust clinical trials evaluating its efficacy, especially its utility as a frontline therapy. In this study (www.chictr.org.cn, ChiCTR2000031702), we designed ruxolitinib as a first-line agent for pediatric HLH and stratified the treatment based on its early response. Fifty-two newly diagnosed patients were enrolled. The overall response rate (ORR) of ruxolitinib monotherapy (day 28) was 69.2% (36/52), with 42.3% (22/52) achieving sustained complete remission (CR). All responders achieved their first response to ruxolitinib within 3 days. The response to ruxolitinib was significantly associated with the underlying etiology at enrollment (P = .009). Epstein-Barr virus (EBV)-HLH patients were most sensitive to ruxolitinib, with an ORR of 87.5% (58.3% in CR). After ruxolitinib therapy, 57.7% (30/52) of the patients entered intensive therapy with additional chemotherapy. Among them, 53.3% (16/30) patients achieved CR, and 46.7% (14/30) patients dominated by chronic active EBV infection-associated HLH (CAEBV-HLH) developed refractory HLH by week 8. The median interval to additional treatment since the first ruxolitinib administration was 6 days (range, 3-25 days). Altogether, 73.1% (38/52) of the enrolled patients achieved CR after treatment overall. The 12-month overall survival (OS) for all patients was 86.4% (95% confidence interval [CI], 77.1% to 95.7%). Ruxolitinib had low toxicity and was well tolerated compared with intensive chemotherapy. Our study provides clinical evidence for ruxolitinib as a frontline agent for pediatric HLH. The efficacy was particularly exemplified with stratified regimens based on the early differential response to ruxolitinib. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR2000031702.
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Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Nitrilos , Pirazoles/efectos adversos , PirimidinasRESUMEN
OBJECT: Goal of this research was to investigate values of serum cytokines in childhood HLH with different triggers, with the expectation to find secretion spectrum of 5 main types of underlying diseases. METHOD: 118 newly diagnosed HLH were included, and serum concentrations of 6 cytokines were tested before treatment began. Absolute cytokine levels and ratios between them were then studied in the HLH groups collectively and separately RESULTS: In general, IFN-γ, IL-10 and IL-6 showed differences among 5 HLH groups. Specifically, relative levels of these three cytokines to each other were meaningful in distinguishing 4 types of HLH. Level of IL-6 was higher than those of IFN-γ or IL-10 in HLH driven by Systemic auto-inflammatory disorders (SAIDs) or Langerhans Cell Histiocytosis (LCH), while primary HLH and EBV-HLH shared elevated ratio of IL-10 to IL-6. Although more than one distinctive ratios were found in 3 HLH groups, combination of these parameters didn't offer optimal balance between sensitivity and specificity. CONCLUSION: As a group of easily gained laboratory findings, cytokine levels were reliable in the procedure of roughly classifying HLH cases with the help of patients' clinical phenotype. However, adequate data is still needed to explore the significance of these indicators in identifying one particular underlying disease accurately.
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Citocinas/sangre , Linfohistiocitosis Hemofagocítica/sangre , Células TH1/metabolismo , Células Th2/metabolismo , Adolescente , Recuento de Células Sanguíneas/métodos , Niño , Preescolar , Femenino , Humanos , Lactante , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Masculino , Sensibilidad y Especificidad , Balance Th1 - Th2/fisiologíaRESUMEN
BACKGROUND: Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in RAB27A gene. It is primarily characterized by a combination of partial albinism, hemophagocytic lymphohistiocytosis (HLH) or other immunodeficiency. However, neurological involvement at onset in GS2 and treatment has rarely been described. CASE PRESENTATION: We describe a 3-year-old boy with GS2 in an Asian Chinese family. He presented with progressive neurological abnormalities following unremitting fever at onset. He developed HLH during the clinical course. A novel homozygous mutation (c.1 A > G) in RAB27A gene was subsequently identified. He was then treated by HLH-1994 protocol combined with ruxolitinib and experienced a dramatic remission. He subsequently underwent a successful haploidentical hematopoietic stem cell transplantation and stayed at a good condition. CONCLUSIONS: We reported an atypical form of GS2 manifesting as severe central nervous system involvement at onset and subsequent HLH, which was successfully rescued in time. This case also highlights the need for early consideration of immunologic and genetic evaluation for HLH in unexplained neuroinflammation in the diagnostic work up.
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Linfohistiocitosis Hemofagocítica , Piebaldismo , Enfermedades de Inmunodeficiencia Primaria , Preescolar , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/genética , Linfohistiocitosis Hemofagocítica/terapia , Masculino , Piebaldismo/complicaciones , Piebaldismo/diagnóstico , Piebaldismo/genética , Proteínas rab27 de Unión a GTP/genéticaRESUMEN
Hemophagocytic lymphohistiocytosis (HLH) is an immune-regulatory disorder characterized by excessive production of inflammatory cytokines. The treatment recommendations of the HLH-1994 and HLH-2004 protocols have long been used in HLH therapy, but some patients still do not respond well to or have unacceptable side effects from conventional therapies. It is believed that cytokine-targeted strategies that directly target disease-driving pathways will be promising options for HLH. This prospective study aimed to investigate the efficacy and safety of ruxolitinib, a Janus kinase (JAK) 1/2 inhibitor, as a front-line therapy in children with secondary HLH. Twelve newly diagnosed patients without previous treatment were enrolled in this study with a median follow-up of 8.2 (7.1-12.0) months, including 8 cases of Epstein-Barr virus associated HLH (EBV-HLH), 2 cases of autoinflammatory disorder (AID)- associated HLH, and 2 cases of unknown etiology. Patients received oral ruxolitinib dosed on 2.5 mg, 5 mg or 10 mg twice daily depending on the body weight for 28 consecutive days. The overall response rate at the end of treatment (day 28) was 83.3% (10/12), with 66.7% (8/12) in complete response (CR), 8.3% (1/12) in partial response (PR), and 8.3% (1/12) in HLH improvement. Among the patients achieving CR, 87.5% (7/8) maintained CR condition for>6 months, and one patient with EBV-HLH relapsed following CR. For the EBV-HLH subgroup, all 8 patients responded to ruxolitinib, with a CR rate of 75% and a PR rate of 25%. Two patients with AID-associated HLH had quite different responses, with one showing reversal of the HLH abnormalities soon and the other showing no improvement, as did the two cases of unknown etiology. Patients who had no response or discontinued ruxolitinib all responded well to the subsequent HLH-1994 regimen. The expected 6-month event-free survival (EFS) rate was 58.3%±10.2%. No serious adverse effects were reported. Our study provides further support for the possibility of ruxolitinib targeted therapy for secondary HLH in children. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR2000029977.
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Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Herpesvirus Humano 4 , Humanos , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Nitrilos , Proyectos Piloto , Estudios Prospectivos , Pirazoles , PirimidinasRESUMEN
PURPOSE: We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). MATERIALS AND METHODS: A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. RESULTS: The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO- group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. CONCLUSION: Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.
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Histiocitosis de Células de Langerhans/tratamiento farmacológico , Imidazoles/uso terapéutico , Oximas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/uso terapéutico , Niño , Preescolar , China , Femenino , Histiocitosis de Células de Langerhans/patología , Humanos , Imidazoles/farmacología , Lactante , Recién Nacido , Masculino , Oximas/farmacología , Proteínas Proto-Oncogénicas B-raf/farmacología , Estudios RetrospectivosRESUMEN
BACKGROUND: Perforin (PRF1) gene mutation can cause the onset of hemophagocytic lymphohistiocytosis (HLH). It has reported that PRF1 Ala91Val polymorphism was related with HLH risk. In the meta-analysis, we aim to evaluate the association between PRF1 Ala91Val polymorphism and HLH risk. METHODS: We accomplished a meta-analysis of six published case-control studies including 391 patients with HLH and 975 controls. We evaluated the quality of each study through Newcastle-Ottawa Scale (NOS). Data analysis was performed with Stata software. RESULTS: In general, all studies were of high quality (NOS score higher than 7). There were statistically significant between the PRF1 Ala91Val polymorphism and HLH risk though the pooled analysis [for Ala/Val vs. Ala/Ala: pooled odds ratio (OR) = 3.22, 95% confidence interval (CI) 1.08-9.56, P = 0.035, random model; for Ala/Val + Val/Val vs. Ala/Ala: pooled OR = 2.96, 95% CI 1.14-7.69, P = 0.025, random model]. Furthermore, sensitivity analysis also revealed a relationship between PRF1 Ala91Val polymorphism and HLH risk (for Ala/Val vs. Ala/Ala: pooled OR = 5.236, 95% CI 2.72-10.08, P < 0.000, I2 = 12.1%, Pheterogeneity = 0.332; for Ala/Val + Val/Val vs. Ala/Ala, pooled OR = 4.856, 95% CI 2.66-8.85, P < 0.000, I2 = 5.9%, Pheterogeneity = 0.373). Funnel plot and Egger's test did not indicate obvious published bias (P = 0.841 for Ala/Val vs. Ala/Ala; P = 0.284 for Ala/Val + Val/Val vs. Ala/Ala). CONCLUSION: This meta-analysis indicated that PRF1 Ala91Val polymorphism affects the factor for developing HLH and future studies of PRF1 Ala91Val on the onset of HLH will be guaranteed.
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Linfohistiocitosis Hemofagocítica/genética , Perforina/genética , Humanos , Polimorfismo GenéticoRESUMEN
Trefoil factor 3 (TFF3) is involved in cell adhesion, motility and apoptosis, regulates mucosal immunity and maintains the functional integrity of intestinal epithelia. The upregulation of TFF3 expression in the weaning rat intestine attracted our interest. The present study hypothesized that TFF3 may serve a role in preventing diarrhea in weaning piglets, which is an important consideration in the pig farming industry. Previous recombinant TFF3 protein expression yields obtained from Escherichia coli were too low and the bioactivity of the protein was poor. Hence, this expression system was unsuitable for industrial applications. The present study explored the production of recombinant sus scrofa TFF3 in a Brevibacillus choshinensis (B. choshinensis) expression system, aiming to enhance the expression level of bioactive protein. To achieve this, the sus scrofa TFF3-encoding gene fragment was fused into an E. coli-Brevibacillus shuttle vector pNCMO2. High levels of TFF3 (30 mg/l) were produced and secreted into the B. choshinensis culture medium in soluble form with a molecular mass of 13.6 kDa and high immunoreactivity in western blotting. Thus, Brevibacillus may be used to produce useful mucosal factors for biochemical analyses and mucosal protection, and in industrial applications to produce novel inhibitors of diarrhea.
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INTRODUCTION: The threshold of serum ferritin (SF) level listed in diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH) of HLH-2004 has a low specificity. The goal of this research was to evaluate the role of admission SF in HLH diagnostic procedure and to find an appropriate threshold for a HLH suspected cohort with fever. METHODS: All patients admitted to Beijing Children's Hospital during the period of September 1, 2015 and July 31, 2016 with fever and SF tested at admission were included in this study. The significance of SF in HLH diagnosis and its relationships with HLH-relevant clinical characteristics were studied. RESULTS: Among 357 patients, 39 HLH cases were diagnosed (24 EBV-related HLH, 13 unknown etiologies triggered HLH, and two familial HLH). The best cutoff value of admission SF was 934 ng/mL, with sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) being 87.2%, 88.4%, 47.9%, and 98.3%, respectively. Compared to 500 ng/mL, specificity and PPV of the new SF standard in HLH diagnose increased by 11.7% and 14.0%, which indicated improvements in diagnostic ability of "non-HLH" and in veracity of "HLH" identification. Among four HLH patients whose admission SF was between 500 ng/mL and 934 ng/mL, HLH diagnosis was guaranteed by other laboratory results in two patients; however, possible misdiagnosis was made in the rest two patients. CONCLUSION: Elevated cutoff value of admission SF level seems to be more appropriate for distinguishing HLH in patients with fever. The exact cutoff value of SF level at diagnosis needs to be determined.
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Ferritinas/sangre , Linfohistiocitosis Hemofagocítica/sangre , Linfohistiocitosis Hemofagocítica/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , MasculinoAsunto(s)
Enfermedades del Sistema Nervioso Central/etiología , Linfohistiocitosis Hemofagocítica/diagnóstico , Niño , Femenino , Humanos , Lactante , Linfohistiocitosis Hemofagocítica/complicaciones , Linfohistiocitosis Hemofagocítica/genética , Imagen por Resonancia Magnética , Masculino , Mutación , Perforina/genéticaRESUMEN
BACKGROUND: Central nervous system (CNS) involvement is found in many patients with hemophagocytic lymphohistiocytosis (HLH). In this study, we mainly analyzed neurological symptoms, imaging findings, cerebrospinal fluid (CSF), and their relationship with outcomes of HLH children. METHODS: Related data of 179 Chinese pediatric patients with HLH admitted to our center from January 2010 to December 2015 were analyzed retrospectively. Diagnosis and treatment were based on the HLH-2004 protocol. Two-tailed Chi-squared test was used to compare between different groups, and Kaplan-Meier survival curves were used to analyze the overall survival (OS) of patients with HLH. RESULTS: In the present study, 21.2% (38/179) of total patients had neurological symptoms including seizure, irritability, somnolence, and unconsciousness. There were 80 (50.0%, excluding 19 patients without imaging data) patients with cranial imaging abnormalities. There were 14.7% (17/116, excluding 63 patients who did not accept lumbar puncture) of patients with abnormal CSF results. CNS involvement is defined as abnormalities in one or more of CNS symptoms, radiological findings, and CSF. Thus, 60.3% of them had CNS involvement. As for the prognosis, the median follow-up time was 3.2 years (17 lost to follow-up). The probable 3-year OS of children was higher without CNS involvement (86.0% ± 4.6%) than those with CNS involvement (68.9% ± 4.9%, hazard ratio [HR] = 2.286, P = 0.019). Among them, the probable 3-year OS of children without CNS symptoms was 76.0% ± 3.8%, higher than with CNS symptoms (59.5% ± 8.1%, HR = 2.147, P = 0.047). The 3-year OS of children with abnormal CSF was 64.7% ± 11.6%, compared with normal CSF (85.1% ± 3.7%, HR = 0.255, P = 0.038). CONCLUSIONS: HLH patients with CNS involvement might have worse outcomes compared with those without CNS involvement, and CNS symptoms and CSF changes are more important to access the prognosis than imaging abnormality.
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Enfermedades del Sistema Nervioso Central/etiología , Linfohistiocitosis Hemofagocítica/complicaciones , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , ConvulsionesRESUMEN
BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an interstitial primary pulmonary disease, characterized by Langerhans cell proliferation. It is easily misdiagnosed in children. This study aimed to characterize the clinical manifestations and features of PLCH by retrospective analysis. METHODS: A retrospective analysis was performed in 117 PLCH patients out of 338 LCH patients who were admitted in our center from November 2006 to October 2013. Variables between two groups were compared by Mann-Whitney U-test and Chi-square test. Kaplan-Meier curves were constructed to compare the survival rates and Cox regression to evaluate the effect of risk factors. RESULTS: The median age of PLCH group was significantly lower than that of non-PLCH group (18.63 months vs. 43.4 months, P < 0.001). All PLCH children had other organ involvement and only 11 cases (9.4%) had respiratory symptoms. The most common radiologic finding was cystic lesions (29 cases, 24.8%). Pulmonary function abnormalities were dominated by obstructive ventilatory dysfunction (63 cases, 82.9%). The 5-year overall survival (OS) of PLCH children was 93.6% ± 2.3% and the event-free survival (EFS) was 55.7% ± 5.2%. Among the 38 cases with progressed or relapsed disease, five cases (13.2%) were due to progression or recurrence of lung damage. The 5-year OS of PLCH children with "risk organ" involvement was significantly lower than those without "risk organ" involvement (86.0% ± 4.9% vs. 100%, χ2 = 8.793, P = 0.003). The difference of EFS between two groups was also significant (43.7% ± 7.7% vs. 66.3% ± 6.5%, χ2 = 5.399, P = 0.020). The "risk organ" involvement had a significant impact on survival (hazard ratio = 1.9, P = 0.039). CONCLUSIONS: PLCH mainly occurs in young children, and only a small percentage of patients have respiratory symptoms. They generally have other organ involvement. Most of PLCH children have a good prognosis and most lung lesions could have improved or stabilized. Management of "risk organ" involvement is the key point to improving EFS.
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Histiocitosis de Células de Langerhans/diagnóstico , Enfermedades Pulmonares/etiología , Niño , Preescolar , Femenino , Histiocitosis de Células de Langerhans/complicaciones , Humanos , Lactante , Células de Langerhans , Pulmón/fisiopatología , Masculino , Estudios RetrospectivosRESUMEN
Signal transducer and activator of transcription 5 (STAT5) is an important transcription factor existing in the cytoplasm of various types of cells. Once activated, STAT5 dimers translocate into nucleus and bind to the corresponding DNA sequence to regulate the transcription of its target genes. There are two isoforms of STAT5: STAT5A and STAT5B with 96% sequence homology and are encoded by two closely related but different genes. Studies have shown that STAT5 can regulate the survival, proliferation, differentiation and death of hematopoietic cells. Furthermore, elevated activation of STAT5 was found in many malignant hematologic diseases and therefore raised the possibility that STAT5 may be used as a new therapeutic target for blood related diseases. This review discusses the regulatory role of STAT5 in hematopoietic cells and its effect on the occurrence and development of blood diseases.