Background The clinical characteristics of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis （EBV-HLH） are largely unreported in the pediatric patients in mainland of China. The main aim of this study...Background The clinical characteristics of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis （EBV-HLH） are largely unreported in the pediatric patients in mainland of China. The main aim of this study was to recognize the clinical features of EBV-HLH in children and to explore its prognosis and risk factors. Methods A retrospective study was performed on 78 pediatric patients with EBV-HLH who were admitted to Beijing Children＇s Hospital between 2003 and 2008. All patients＇ medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory and outcome information was collected. Statistical analysis was conducted via multivariate and univariate analysis. Results The age of onset peaked between 1-2 years and boys were more likely developed EBV-HLH. EBV-HLH occurred mainly in the serological pattern with EBV nuclear antigen （EBNA） positive （70.5%）. The overall fatality of the disease was 56.7%. Twelve of the 39 fatalities （30.8%） died rapidly within 2 months after diagnosis. Multivariate analysis revealed that not receiving chemotherapy （P=0.002）, 〉4 weeks of illness prior to diagnosis （P=0.004）, and albumin levels 〈20 g/L （P=-0.045） significantly predicted an increased fatality risk. Conclusions EBV-HLH is a severe disease with a high fatality rate that occurs mainly in the serological pattern with EBNA positive. Early initiation of chemotherapy and timely diagnosis significantly improves survival rate. Practical strategies should focus on reducing the likelihood of early death.展开更多
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, cerebrospin...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 H LH-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.展开更多
Background Recent studies have reported germline mutations in the perforin gene （PRF1） in some types of hemophagocytic lymphohistiocytosis （HLH）. However, the prevalence of PRF1 mutations in HLH in Chinese pediatr...Background Recent studies have reported germline mutations in the perforin gene （PRF1） in some types of hemophagocytic lymphohistiocytosis （HLH）. However, the prevalence of PRF1 mutations in HLH in Chinese pediatric patients has not been extensively studied. The aim of this study was to investigate the prevalence of mutations and sequence variations in the PRF1 gene in Chinese pediatric patients with HLH. Methods Polymerase chain reaction （PCR） was performed with five pairs of primers for the coding exons and the flanking intron sequences of PRF1. Sequencing of PCR products was subsequently applied in 30 pediatric patients with HLH and in 50 controls. Results Three heterozygous mutations in a coding region were found, which resulted in amino acid changes （C102F, S108N and T450M） in three patients. These mutations were not detected in control subjects. One patient had compound heterozygous mutations （S108N and T450M） in PRF1 as the background defect, and documented familial HLH type 2 （FHL2）. One synonymous sequence variant （Q540Q） was observed in one patient but not in the controls. Two SNPs （A274A, H300H） in the coding region were detected in HLH patients and controls, but without differences in the heterozygosity rate between the two groups （P 〉0.05 for all comparisons）. Conclusions We have identified three patients with three heterozygous missense mutations in PRF1; two of those three mutations （C102F and S108N） have so far been found only from Chinese patients. These findings are useful in evaluating the prevalence of PRF1 mutations in Chinese pediatric patients with HLH, and to correlate their genotype with phenotype. Some patients without familial history probably have primary HLH, which should be suspected even beyond the usual age range.展开更多
Background： Hemophagocytic lymphohistiocytosis （HLH） is a life-threatening clinical syndrome. Central nervous system （CNS） involvement is a severe complication, which can lead to rapid disease development and hig...Background： Hemophagocytic lymphohistiocytosis （HLH） is a life-threatening clinical syndrome. Central nervous system （CNS） involvement is a severe complication, which can lead to rapid disease development and higher morality. However, this has not been given enough attention in adult HLH. Therefore, we carried out this study to analyze the clinical features, laboratory findings, treatment outcomes, and other characteristics of adult HLH with CNS involvement. Methods： A retrospective analysis of 96 adult patients with HLH combined with CNS involvement between June 2003 and December 2016 was conducted. Clinical features, cerebrospinal fluid （CSF） features, image changes, and therapeutic outcomes were analyzed. Results： Among the 96 patients, 86 had various CNS symptoms and 33 （38.4%） had already presented symptoms before the HLH diagnosis was confirmed. A total of 59 patients received CSF examinations and showed abnormalities in 23 patients （39.0%）. Seventy patients received imaging examinations and the results showed fifty patients with imaging changes （71.4%）. Fifty-seven patients received multiple rounds of repeated intrathecal injection therapy and 35 patients improved （61.4%）. As for the multiple analyses of effective factors on survival time, the results showed that the effects of combined Epstein-Barr virus （EBV） infection （P = 0.026, Exp（B） 95% confidence interval [CI] [1.108, 4.823） and intrathecal injection therapy （P = 0.013, Exp（B） = 0.422, 95% CI [0.214, 0.831]） survival time of the CNS-HLH patients were significant. 2.309, on the Conclusions： Complication with EBV infection is a risk factor, and intrathecal injection is a protective factor. CNS involvement in HLH is not rare, which can result in a poor prognosis. Multiple rounds of repeated intrathecal injection therapy can improve the prognosis of CNS-HLH patients.展开更多
基金This study was supported by the grants from Beijing Natural Science Foundation （No. 7072026） and Scientific Research Program of Beijing Municipal Commission of Education （No. KM200710025023）.
文摘Background The clinical characteristics of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis （EBV-HLH） are largely unreported in the pediatric patients in mainland of China. The main aim of this study was to recognize the clinical features of EBV-HLH in children and to explore its prognosis and risk factors. Methods A retrospective study was performed on 78 pediatric patients with EBV-HLH who were admitted to Beijing Children＇s Hospital between 2003 and 2008. All patients＇ medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory and outcome information was collected. Statistical analysis was conducted via multivariate and univariate analysis. Results The age of onset peaked between 1-2 years and boys were more likely developed EBV-HLH. EBV-HLH occurred mainly in the serological pattern with EBV nuclear antigen （EBNA） positive （70.5%）. The overall fatality of the disease was 56.7%. Twelve of the 39 fatalities （30.8%） died rapidly within 2 months after diagnosis. Multivariate analysis revealed that not receiving chemotherapy （P=0.002）, 〉4 weeks of illness prior to diagnosis （P=0.004）, and albumin levels 〈20 g/L （P=-0.045） significantly predicted an increased fatality risk. Conclusions EBV-HLH is a severe disease with a high fatality rate that occurs mainly in the serological pattern with EBNA positive. Early initiation of chemotherapy and timely diagnosis significantly improves survival rate. Practical strategies should focus on reducing the likelihood of early death.
基金This work was supported by grants from the Technology Key Projects （No. 2017ZX09304029004）, the Beijing Municipal Science and Technology Commission （No. Z171100001017050）, the National Natural Science Foundation of China （No. 81700186）, the Scientific Research Common Program of Beijing Municipal Commission of Education （No. KM201710025019）, the Pediatric Project of Ai You Foundation （No. AYEK201802）, and the Talent Training Project-Fostering Fund of National Natural Science Foundation of Beijing Children＇s Hospital, Capital Medical University （No. GPY201713）.
文摘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 H LH-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.
文摘Background Recent studies have reported germline mutations in the perforin gene （PRF1） in some types of hemophagocytic lymphohistiocytosis （HLH）. However, the prevalence of PRF1 mutations in HLH in Chinese pediatric patients has not been extensively studied. The aim of this study was to investigate the prevalence of mutations and sequence variations in the PRF1 gene in Chinese pediatric patients with HLH. Methods Polymerase chain reaction （PCR） was performed with five pairs of primers for the coding exons and the flanking intron sequences of PRF1. Sequencing of PCR products was subsequently applied in 30 pediatric patients with HLH and in 50 controls. Results Three heterozygous mutations in a coding region were found, which resulted in amino acid changes （C102F, S108N and T450M） in three patients. These mutations were not detected in control subjects. One patient had compound heterozygous mutations （S108N and T450M） in PRF1 as the background defect, and documented familial HLH type 2 （FHL2）. One synonymous sequence variant （Q540Q） was observed in one patient but not in the controls. Two SNPs （A274A, H300H） in the coding region were detected in HLH patients and controls, but without differences in the heterozygosity rate between the two groups （P 〉0.05 for all comparisons）. Conclusions We have identified three patients with three heterozygous missense mutations in PRF1; two of those three mutations （C102F and S108N） have so far been found only from Chinese patients. These findings are useful in evaluating the prevalence of PRF1 mutations in Chinese pediatric patients with HLH, and to correlate their genotype with phenotype. Some patients without familial history probably have primary HLH, which should be suspected even beyond the usual age range.
文摘Background： Hemophagocytic lymphohistiocytosis （HLH） is a life-threatening clinical syndrome. Central nervous system （CNS） involvement is a severe complication, which can lead to rapid disease development and higher morality. However, this has not been given enough attention in adult HLH. Therefore, we carried out this study to analyze the clinical features, laboratory findings, treatment outcomes, and other characteristics of adult HLH with CNS involvement. Methods： A retrospective analysis of 96 adult patients with HLH combined with CNS involvement between June 2003 and December 2016 was conducted. Clinical features, cerebrospinal fluid （CSF） features, image changes, and therapeutic outcomes were analyzed. Results： Among the 96 patients, 86 had various CNS symptoms and 33 （38.4%） had already presented symptoms before the HLH diagnosis was confirmed. A total of 59 patients received CSF examinations and showed abnormalities in 23 patients （39.0%）. Seventy patients received imaging examinations and the results showed fifty patients with imaging changes （71.4%）. Fifty-seven patients received multiple rounds of repeated intrathecal injection therapy and 35 patients improved （61.4%）. As for the multiple analyses of effective factors on survival time, the results showed that the effects of combined Epstein-Barr virus （EBV） infection （P = 0.026, Exp（B） 95% confidence interval [CI] [1.108, 4.823） and intrathecal injection therapy （P = 0.013, Exp（B） = 0.422, 95% CI [0.214, 0.831]） survival time of the CNS-HLH patients were significant. 2.309, on the Conclusions： Complication with EBV infection is a risk factor, and intrathecal injection is a protective factor. CNS involvement in HLH is not rare, which can result in a poor prognosis. Multiple rounds of repeated intrathecal injection therapy can improve the prognosis of CNS-HLH patients.
