Hemophagocytic Syndrome In Patients Research Articles

Clinical characteristics and prognostic factors of 75 cases with acquired hemophagocytic syndrome

ABSTRACTObjectivesThe study's aim was to enhance awareness of acquired hemophagocytic syndrome (HPS) in adults by analyzing clinical features, and investigating the relationship between factors such as the Systemic Inflammation Index (SII) and the prognosis of HPS.MethodsClinical characteristics, survival data, and prognostic factors of 75 HPS patients admitted to our hospital between January 2012 and October 2022 were analyzed.ResultsIn the high SII group, red blood cells, white blood cells, platelets, neutrophils, fibrinogen, and CD4 + cell activity were higher, and survival time was longer compared to the low SII group. Conversely, total bilirubin and direct bilirubin were higher in the low SII group (P ≤ 0.05). After applying the log-Rank or Breslow tests, HPS patients in the high SII group and those following the HLH-2004 protocol experienced a notably longer survival time. (χ2 = 4.291, P < 0.05; χ2 = 5.210, P < 0.05). Patients with poor prognosis showed higher age of onset, elevated levels of total, direct, and indirect bilirubin, and a greater rate of EBV infection, but reduced levels of red blood cells, platelets, hemoglobin, albumin, globulin, and HLH-2004 protocol usage rate(P < 0.05). Multivariate analysis and ROC curve results indicate that special attention is needed for patients with platelets < 42.5 × 109/L, albumin < 27.7 g/L, fibrinogen < 1.085 g/L, those not following the HLH-2004 protocol, and those who are EBV (+).Discussion and ConclusionEarly diagnosis and following the HLH-2004 protocol are essential for patients with HPS clinical manifestations to improve prognosis. Additional research is necessary to examine the link between SII and HPS patients’ prognosis.

A clinical analysis of hemophagocytic syndrome secondary to autoimmune diseases.

This study aimed to analyze the differences of etiologies and clinical features between patients with autoimmune-associated hemophagocytic syndrome (AAHS) and those with other underlying diseases of hemophagocytic syndrome (HPS). The retrospective study was performed with 130 HPS patients (70 males, 60 females; mean age: 50.4±18.1 years; range, 13 to 85 years) between January 1st, 2011, and April 1st, 2022. The patients fulfilled at least five of the eight criteria proposed by the Histiocytosis Society in 2004. The underlying diseases related to HPS were divided into four categories: autoimmune, infection, malignancy and idiopathic diseases. And the clinical manifestations, laboratory examinations, treatments, and prognosis were analyzed respectively. Nineteen (14.6%) patients had AAHS, 45 (34.6%) had infection-associated HPS, 57 (43.8%) had malignancy-associated HPS, and nine (6.9%) had idiopathic HPS. The most common symptoms of HPS were unremitting fever in 123 (94.6%) of 130 patients and splenomegaly in 92 (70.8%). All patients manifested a decline of at least two lineages of hematopoietic cells. The absolute values of T cells and B cells of AAHS were significantly higher than that of malignancy-associated HPS. The levels of soluble CD25 (interleukin-2 receptor) of AAHS were the lowest among all-cause HPS (p<0.05). The all-cause mortality rate of hospitalized patients with HPS was 46.2%. The patients with AAHS had a better prognosis compared to other etiologies (odds ratio [OR]=0.091, 95% confidence interval [CI]: 0.011-0.775, p=0.028). Epstein-Barr virus infection (OR=4.761, 95% CI: 1.619-14.004, p=0.005) and pulmonary involvement (OR=4.555 95% CI: 1.524-13.609, p=0.007) were independent predictors of poor outcome in HPS. Thrombocytopenia (OR=0.978, 95% CI: 0.968-0.999, p=0.040) had a boundary effect on prognosis. Patients with HPS secondary to autoimmune disease have better outcomes compared to patients complicated with Epstein-Barr virus infection or pulmonary involvement.

Renal involvement as a unique manifestation of hemophagocytic syndrome.

Renal-limited hemophagocytic syndrome (HPS) is a rare clinical setting characterized by abnormal activation of the immune system. Fever associated with pancytopenia, hepatosplenomegaly with liver dysfunction, and hypofibrinogenemia are usually observed in HPS. From a histological level, the presence of non-malignant macrophages infiltrating bone marrow and organs represents the hallmark of this condition. Non-malignant macrophages are associated with phagocytizing activities involving other blood cells. While primary HPS is usually associated with inherited dysregulation of the immune system, secondary HPS usually occurs in the context of infection or is linked to a neoplastic process. Clinical presentation varies and can potentially lead to life-threatening settings. While renal involvement has frequently been reported, however, detailed descriptions of the kidney manifestations of HPS are lacking. More critically, the diagnosis of HPS is rarely supported by renal biopsy specimens. We report four rare cases of biopsy-proven renal-limited HPS in patients presenting with acute kidney injury (AKI). The available evidence on this topic is critically discussed in light of the possible emergence of an autonomous entity characterized by an isolated kidney involvement.

Acute circulatory failure in critically ill patients with hemophagocytic syndrome.

Hemophagocytic syndrome (HS) is a rare life-threatening condition that can lead to multi organ failure and shock. Acute circulatory failure in these patients has been poorly studied. Objectives of this study were to describe characteristics of HS patients with shock, prognostic factors and impact of etoposide infusion on hemodynamic parameters. This is a monocenter, retrospective, observational cohort study in a French tertiary intensive care unit (ICU). All adult critically ill patients with HS managed in the ICU between 2007 and 2017, requiring vasopressors (norepinephrine) and etoposide infusion. Thirty-four patients were included. Two-third (n = 25) were of male gender and median age was 48 years [IQR 34-62]. Shock (n = 14, 41%) and acute respiratory failure (n = 8, 23.5%) were the main initial reasons for ICU admission. The most common HS trigger was underlying hematological malignancy (n = 26; 76%), followed by infectious diseases in 3 patients (9%) and auto immune diseases in 2 (6%) patients. Median SOFA score at ICU admission was 14 [10-17]. A majority of patients required mechanical ventilation (n = 29, 85%) and initial median lactate level was 3.7 mmol/L [2.9-6.9]. Hospital mortality rate was 53% (n = 18) and was associated with SOFA score and renal replacement therapy in univariate analysis. All patients received broad spectrum antibiotics under suspicion of septic shock. In 17 patients, 21 nosocomial infections were documented, mainly from bacterial origin. Etoposide infusion was followed by decreased norepinephrine doses despite an increase in lactate level, while no degradation in mean arterial pressure, heart rate or renal function were identified. Hospital mortality remains high in critically ill HS patients with shock, but a significant improvement of hemodynamic parameters is observed following etoposide infusion, suggesting that an aggressive initial supportive care is crucial in these patients.

Differential Diagnosis of Hemophagocytic Syndrome by 18F-FDG PET/CT: A Meta-Analysis.

Hemophagocytic syndrome (HPS) is a rare disease in clinical practice, and there are often cases of delayed diagnosis. At present, researchers have applied 18F-FDG PET/CT in the differential diagnosis of HPS, but no consensus has been formed. Therefore, this study aims to systematically evaluate the application value of 18F-FDG PET/CT in the diagnosis of HPS patients. PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wangfang database (Wangfang), and Chinese Biomedical Network (CBM) were searched to collect the relevant studies of 18F-FDG PET/CT in the diagnosis of HPS. Data from the articles were screened and extracted for meta-analysis using Stata16.0 software. A total of 10 retrospective studies, including 300 patients, were included in this meta-analysis. The meta-analysis results showed that the pooled sensitivity was 0.82 (95% CI: 0.67–0.95), specificity was 0.72 (95% CI: 0.51–0.86), positive likelihood ratio was 2.89 (95% CI: 1.46–5.75), positive likelihood ratio was 0.25 (95% CI: 0.12–0.54), diagnostic odds ratio was 2.89 (95% CI: 1.46–5.75), and AUC was 0.84 (95% CI: 0.81–0.87). The SUVmax in the liver, spleen, lymph nodes, and bone marrow of HPS patients was greater than 2.5, and the SUVmax in the spleen, lymph nodes, and bone marrow of malignant HPS patients was higher than that of benign HPS patients. The difference was statistically significant (P < 0.05). According to the existing literature evidence, 18F-FDG PET/CT is an effective method for diagnosing HPS.

How to Identify Patients at High Risk of Developing Nasal-Type, Extranodal Nature Killer/T-Cell Lymphoma-Associated Hemophagocytic Syndrome.

Nasal-type, extranodal nature killer (NK)/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is a rare and life-threatening disease, requiring investigation of risk stratification. We conducted a retrospective study and proposed nomograms to predict NK/T-LAHS. The discriminative ability and calibration of the nomograms for prediction were tested using C statistics and calibration plots. We analyzed 533 patients with extranodal NK/T-cell lymphoma (ENKTL), out of which 71 were diagnosed with hemophagocytic syndrome (HPS), with a cumulative incidence of 13.3%. Significant difference for 2-year survival was found between patients with and without HPS (14.7% vs. 77.5%). Analyses showed that Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, B symptoms, and bone marrow (BM) invasion were significantly associated with NK/T-LAHS. We used these data as the basis to establish a nomogram of risk index for ENKTL (RINK). In 335 patients with available data for Epstein-Barr virus DNA (EBV-DNA), we found high viral copies (≥4,450 copies/ml) were correlated with NK/T-LAHS. When these data were added to RINK, we developed another nomogram that included EBV-DNA data (RINK-E). The nomograms displayed good accuracy in predicting NK/T-LAHS with a C-statistics of 0.919 for RINK and a C-statistics of 0.946 for RINK-E, respectively. The calibration chart also showed an excellent consistency between the predicted and observed probabilities. The proposed nomograms provided individualized risk estimate of HPS in patients with ENKTL.

Mortal Interaction Between Hemophagocytic Syndrome and Newly Developed Heart Failure.

ResumoFundamento:A síndrome hemofagocítica (SHF) é uma síndrome hiperinflamatória debilitante. O status da insuficiência cardíaca (IC) com fração de ejeção preservada (ICFEP) está intimamente relacionado ao aumento da inflamação sistêmica e intramiocárdica.Objetivos:este estudo pretende determinar os preditores de mortalidade e os parâmetros de monitoramento confiáveis nos casos de SHF que desenvolveram a ICFEP durante seu curso clínico.Métodos:Trinta e nove pacientes, diagnosticados com SHF de acordo com os critérios diagnósticos do estudo HLH 2004 com Hscore ≥169, e com aspiração ou biópsia de medula óssea comprovada, foram recrutados retrospectivamente. Foram investigados retrospectivamente os fatores de risco tradicionais, como proteína C reativa sérica, níveis de albumina e ferritina com contagens de linfócitos e plaquetas, e fatores não tradicionais, como relação neutrófilolinfócito (NLR), relação linfócito-monócito (MLR), volume plaquetário médio (MPV) e pró-peptídeo natriurético cerebral N-terminal (NTproBNP). Analisou-se a relação entre os valores laboratoriais alterados ao longo do tempo entre si e com a mortalidade. O nível de significância geral foi de 5%.Resultados:Foi demonstrado que a alteração temporal dos níveis de índice cardiotorácico (ICT), NTproBNP sérico, ferritina, PCR e albumina foram detectados como sendo preditores de mortalidade (p<0,05, para todos) em análise univariada. As contagens de linfócitos e plaquetas com valores de NLR e MPV também foram significativos (p<0,05). A relação entre NT-proBNP e o aumento dos marcadores inflamatórios sistêmicos também foi considerada significativa. Além de fatores de risco tradicionais, os níveis de ferritina sérica, e os níveis de NLR, MLR e MPV foram considerados significativamente correlacionados entre si.Conclusão:Acompanhado de parâmetros de monitoramento confiáveis, o diagnóstico rápido e o tratamento antiinflamatório agressivo com controle rígido de volume podem salvar vidas de pacientes com SHF que sofrem de complicações por ICFEP. O monitoramento rígido da inflamação pode prever o resultado do paciente que sofre de ICFEP.

Hemophagocytic syndrome in patients infected with the human immunodeficiency virus: A study of 15 consecutive patients.

ABSTRACTObjectivesHemophagocytic syndrome (HPS) is characterized by various clinical and biological data derived from cytokine hyperproduction and cell proliferation. The objectives of this study were to evaluate the epidemiological, etiological, clinical and evolutionary characteristics of patients diagnosed with hemophagocytic syndrome and HIV infection, as well as their comparison with data from the literature.Methods-A retrospective descriptive observational study was performed, including all adult patients with a diagnosis of HPS and HIV infection treated in the Infectious Diseases and Tropical Medicine Unit of the Hospital Universitario Insular, Las Palmas, Gran Canaria from June 1, 1998 to December 31, 2018.ResultsAn analysis of this series of case reports of 15 patients showed a higher percentage of males than females, with a mean age of 42 years. With respect to the diagnostic criteria for HPS, presence of fever, cytopenias and hyperferritinemia were a constant in all patients. Clinical neurological manifestations were frequent and clinical respiratory signs and symptoms absent. HPS was confirmed in some patients who were not severely immune-depressed and had undetectable viral loads. Furthermore, 40% of cases were not receiving ART. The most frequent triggering causes of HPS were viral, especially HHV-8. In addition, two new HPS triggers were identified: Blastocystis dermatitidis and Mycobacterium chelonae.ConclusionAdministration of treatment in HPS is arbitrary. This, together with the high mortality rate and the fact that it is underdiagnosed, indicates the importance of conducting future studies.

Dectection of Erythrocyte Life and Analysis of Its Effect on the Anemia in Patients with Hemophagocytic Syndrome

To detect the erythrocyte life by breath carbon monoxide assay and to analyze the effect of erythrocyte life on the anemia in patients with hemophagocytic syndrome. The breath carbon monoxide test and erythrocyte life assay were performed for 20 cases of hemophagocytic syndrome, at the same time the detection of 20 healthy persons was used as control. The difference of anemia-related indexes was compared between hemophagocytic syndrome patients and healthy persons. The average erythrocyte life of patients with hemophagocytic syndrome was 45.3 days, which was 65% shorter than that of healthy persons. Hemoglobin levels positively correlated with erythrocyte life, while sCD25, breath carbon monoxide concentration and hemophagocytosis negatively correlated with erythrocyte life. Bilirubin level and reticulocyte count showed no correlation with erythrocyte life. Serum level of IL-1β, IL-2, sCD25, IL-6, IL-10, IL-17A, GM-CSF, TNF-α and IFN-γ in patients with newly diagnosed hemophagocytic syndrome were significantly higher than those of healthy persons (P＜0.05). Breath carbon monoxide assay is a rapid and efficient method to assess erythrocyte life. Increased erythrocyte destruction may be an important pathogenic factor for anemia in hemophagocytic syndrome.

Clinical Characteristics of Liver Dysfunction in Patients with Hemophagocytic Syndrome

To explore the clinical feature of liver injury in patients with hemophagocytic syndrome (HPS). The clinical data of 92 patients with HPS in our hospital were analyzed retrospectively, and the characteristics of hepatic lesion and its relationship with prognosis in HPS patients were explored. 92 cases of HPS showed different degrees of liver dysfunction from mild to moderate. The clinical parameters of liver dysfunction included the increased level of LDH (89.13%), AST (64.13%), TBIL (59.78%) and decreased level of ALB (90.22%). Moreover, 76.09% and 67.39% of the patients had the prolonging of APTT and PT respectively. The ALB level of patients in rheumatoid immune group were higher than that in infection, maglinancy and unexplained groups, all with statistically and significant difference (P＜0.05, P＜0.05 and P＜0.01), the ALB level of patients in infection group were statistically and significantly higher than that in unexplained group (P＜0.01). The Fbg level of patients in infection group were lower than that in maglinancy group, unexplained group and rheumatoid immune group, all the differences were statistically significant (P＜0.05, P＜0.01 and P＜0.05). Child-Pugh grading was further carried out in HPS patients with liver disfunction. Survival time of the patients grade A was significantly higher than that of grade B and C of patients. Univariate analysis showed that the patients with LDH≥2000 U/L, ALB＜30 g/L and PT≥15.1 s had a survival time inferior to control patients (P＜0.05, P＜0.01 and P＜0.01, respectively). Multivariate analysis showed that ALB＜30 g/L was an independent adverse prognostic factor for these patients (P＜0.01). Patients with HPS generally have impaired liver function mainly manifested with elevated LDH and AST levels, and declined ALB level, which may correlate with the disease cause and prognosis. Patients with LDH≥2000 U/L, ALB＜30 g/L and PT≥15.1 s have a poorer prognosis and should be treated as soon as possible.

Hemophagocytic Syndrome in Patients Living with HIV

Hemophagocytic Syndrome in Patients Living with HIV

Hemophagocytic syndrome in patients living with HIV: a retrospective study.

Various infectious diseases can hyper-stimulate the immune system, causing hemophagocytic syndrome (HPS). Little is known regarding the accuracy of diagnostic criteria and epidemiological triggering factors in the acquired immunodeficiency syndrome (AIDS) setting. We investigated the major infectious disease triggers of HPS in patients living with human immunodeficiency virus (HIV)/AIDS and determined the accuracy of bone marrow aspiration (BMA). The inclusion criteria were (i) confirmed HIV diagnosis, (ii) bone marrow aspiration, and (iii) a minimum of four HPS criteria. Patients were further classified into those with four presumed HPS criteria, or ≥ 5 confirmed criteria. The disease triggers, accuracy of bone marrow aspiration, and prognosis markers were examined. Presumed HPS was observed in 15/36 patients (41%), and confirmed HPS in 58% (n= 21). The major etiological triggers were infection with Mycobacterium (34%), Cytomegalovirus (14%), Cryptococcus neoformans (11%), and hematological or tumoral disease (11%). BMA demonstrated 93% specificity on screening diagnosis (odds ratio [OR] 12.7, 95% confidence interval [CI] 1.4-115.1, P= 0.01). Ferritin > 5000ng/mL correlated with probability of death in univariate analysis (OR 6.00, 95% CI 1.33-27.05, P =0.02). Ferritin performance as test of death probability presented area under the curve as 0.74 (95% CI 0.56-0.91, P= 0.016). However, neither cluster of differentiation for lymphocyte count nor HIV viral load correlated with patient deaths. Mycobacterium spp. and Cytomegalovirus were the main factors triggering HPS, followed by Cryptococcus neoformans, and hematological and tumoral diseases. High ferritin levels were associated with increased death probability. High specificity was noted with BMA.

Bullous Sweet's syndrome with figurate erythema and cutaneous hemophagocytosis

Abstract A 56-year-old woman presented with multiple blisters on the rim of painful erythematous annular lesions over the trunk and four extremities, accompanied with fever and arthralgia on both ankles and feet. Laboratory studies showed neutrophilia and elevated C-reactive protein level. Skin biopsy revealed exuberant edema of the papillary dermis, extensive neutrophil infiltration, and hemophagocytosis within the dermis. Her symptoms and skin lesions resolved 3 days after initiation of systemic corticosteroids. To the best of our knowledge, this is the first case report of cutaneous hemophagocytosis without additional symptoms of hemophagocytic syndrome in patients with Sweet's syndrome.

FRI-049 - Prevalence and clinical implications of hemophagocytic syndrome in patients with infection-induced acute on chronic liver failure – a retrospective pilot study

FRI-049 - Prevalence and clinical implications of hemophagocytic syndrome in patients with infection-induced acute on chronic liver failure – a retrospective pilot study

Assessment of the HScore for reactive haemophagocytic syndrome in patients with rheumatic diseases

Objectives: Reactive haemophagocytic syndrome (RHS) is a hyperinflammatory disorder often occurring in the background of several disorders such as infections, malignancies, and rheumatic diseases. Recently, a score known as the HScore was developed for the diagnosis of RHS. In the original study, most of the patients had underlying haematological malignancy or infection and the best cut-off value for the HScore was 169 (sensitivity 93%; specificity 86%). In this study we aimed to analyse the performance of the HScore in rheumatic disease-related RHS.Method: The patients with rheumatic disorders evaluated in the Departments of Rheumatology and Paediatric Rheumatology at Hacettepe University, Ankara, Turkey between 2002 and 2014 were reviewed retrospectively. The first group (n = 30) consisted of patients with RHS; the control group (n = 64) included patients with active rheumatic diseases without RHS.Results: In the RHS group, 14 (46.7%) had adult-onset Still’s disease (AOSD), 10 (33.3%) systemic juvenile idiopathic arthritis (SJIA), and six (20%) systemic lupus erythematosus (SLE). The control group (n = 64) consisted of 32 (50%) AOSD, 13 (20.3%) SJIA, and 19 (29.7%) SLE patients. Applying the HScore to the RHS patients, the best cut-off value was 190.5 with a sensitivity of 96.7% and specificity of 98.4%. When we excluded the patients from the control group who had not had bone marrow aspiration (n = 23), the same cut-off (190.5) performed best (sensitivity 96.7%; specificity 97.6%). Applying the 2004 haemophagocytic lymphohistiocytosis (HLH-2004) criteria gave a sensitivity of 56.6% and a specificity of 100% in the whole study group.Conclusions: In our study, a cut-off value for the HScore different from the original study performed better. Further studies are warranted to determine optimum cut-off values in different studies.

The clinical value of F-18 FDG PET/CT in patients with secondary hemophagocytic syndrome

The aim of this study was to investigate the role of F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in diagnosis and prognostic evaluation of secondary hemophagocytic syndrome (HPS). A total of 11 secondary HPS patients examined with 18F-FDG-PET/CT were retrospectively analyzed. The diagnostic value of F-18 FDG PET/CT for malignancy detection was assessed. The values of maximum standardized uptake value (SUV(max)) in spleen (SUVS(p)) and in bone marrow (SUVBM) were measured to analyze their relationship with various laboratorial parameters and clinical outcome of secondary HPS patients. The results showed that 4 out of the 11 patients had malignancies, the sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT for malignancy detection were 100%, 66.7% and 75% respectively, the SUV(max) of spleen and bone marrow showed no significant correlation with laboratorial parameters, a maximum SUVS(p) of 3.10 and a maximum SUVBM of 3.47 were the optimal cutoffs for predicting patients' outcome, the increased uptake of F-18 FDG in the BM and spleen were significantly associated with shorter survival time according to univariate analysis. It is concluded that 18F-FDG PET/CT may especially play an important role in diagnosis and predicting outcome of secondary HPS for the small sample size.

Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy

Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Patients with acute myeloid leukemia may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infections. In a series of 343 patients treated by intensive chemotherapy over a 5-year period in our center, we identified 32 patients (9.3%) with fever, very high ferritin levels, and marrow hemophagocytosis (i.e. patients with hemophagocytic lymphohistiocytosis). Compared to patients without hemophagocytic lymphohistiocytosis, these 32 patients had hepatomegaly, pulmonary or neurological symptoms, liver abnormalities, lower platelet count and higher levels of C-reactive protein as well as prolonged pancytopenia. A microbial etiology for the hemophagocytosis was documented in 24 patients: 14 bacterial infections, 9 Herpesviridae infections and 11 fungal infections. The treatment of hemophagocytic lymphohistiocytosis consisted of corticosteroids and/or intravenous immunoglobulins along with adapted antimicrobial therapy. Patients with hemophagocytic lymphohistiocytosis had a median overall survival of 14.9 months, which was significantly shorter than that of patients without hemophagocytic lymphohistiocytosis (22.1 months) (P=0.0016). Hemophagocytic lymphohistiocytosis was significantly associated with a higher rate of induction failure, mainly due to deaths in aplasia. Hemophagocytic lymphohistiocytosis can be diagnosed in up to 10% of patients with acute myeloid leukemia undergoing intensive chemotherapy and is associated with early mortality. Fever, very high ferritin levels and marrow hemophagocytosis represent the cornerstone of the diagnosis. Further biological studies are needed to better characterize and recognize this syndrome in patients with acute myeloid leukemia.

Hemophagocytic syndrome in patients with unexplained cytopenia: report of 15 cases

To investigate the frequency of hemophagocytic syndrome in a series of patients with otherwise unexplained cytopenia. In this cross-sectional, single-centre study, bone marrow specimens (n=288) were obtained from the patients with unexplained cytopenia. The diagnosis of hemophagocytic syndrome was made according to universally accepted criteria. Characteristics of the patients, as well as the clinical and laboratory findings were reported. Fifteen cases (5.2%) fulfilled the hemophagocytic syndrome criteria, including 8 males (53.3%) and 7 females (46.7%) with a mean age of 39.7±20.7 (range: 14-72) years at the time of diagnosis. The main clinical and laboratory findings were cytopenia (100%), fever (73.3%), hyperferritinemia (66.7%), elevated erythrocyte sedimentation rate (60%), hypertriglyceridemia (60%), organomegaly (53.3%), elevated liver enzymes (53.3%), lymphadenopathy (26.7%), neurological symptoms (20%), and skin rash (13.3%). Two patients (13.3%) died before a diagnosis was made. Our findings indicate that the hemophagocytic syndrome is not a rare pathologic condition in patients with otherwise unexplained cytopenia. Without treatment, the mortality rate may be high.

Outcome of Adult Patients with Hemophagocytic Syndrome: A Tertiary Care Center Experience

AbstractAbstract 1040 Introduction:Hemophagocytic syndrome (HPS) is a rare disorder characterized by fever, splenomegaly, cytopenias, hypofibrinogenemia, hyperferritinemia and hemophagocytosis in the bone marrow or lymph nodes. It is caused by pathologic activation of the immune system, and manifests clinically with signs and symptoms related to extreme inflammation. Primary HPS or familial hemophagocytic lymphohistiocytosis (HLH) occurs predominantly in children (<18 years) due to inherited defects in natural killer and cytotoxic T-cell function. Secondary HPS generally occurs in adults (>18 years) and is precipitated by autoimmune disorders, malignancy and a variety of infections. The results of HLH-94 trial, the largest prospective study in pediatric patients with HLH, reported an estimated 5-year survival of 54%. There is a paucity of information about HPS in adult patients. Methods:Records of all adult (≥ 18 years) patients with a diagnosis of “hemophagocytosis“ or “hemophagocytic syndrome” presenting from January 1996 through December 2011 at Mayo Clinic were reviewed. Our hematopathology database was also analyzed for patients bearing a diagnosis of HPS. Out of a total of 127 patients identified in the database, 50 adult patients were diagnosed to have HPS as per the diagnostic criteria of the HLH-1994 trial (for patients seen prior to 2004), and HLH-2004 trial (for patients seen after 2004). This study was approved by the Institutional Review Board at Mayo Clinic. Results:Baseline characteristics of all patients are shown in Table 1. The median time to diagnosis from the onset of symptoms was 38 days (4–158 days). Secondary HPS was diagnosed in 46 (92%) patients. The causes of secondary HPS are shown in Table 2. Twenty (40%) patients were treated with etoposide containing regimen, 26 (52%) were treated with therapeutic agents directed specifically to the underlying precipitating disease, and 4 (8%) patients did not receive any treatment. No patient in our study underwent a stem cell transplant (SCT). After a median follow-up of 43 months, 36 (72%) patients have died. The causes of death were infection (47%), malignancy (42%), bleeding (8%) and unknown (3%). The median overall survival (OS) for the entire cohort was 1.5 months (95% CI, 0.7–4.5 months). The median OS for patients with malignancy- related HPS was 0.8 months (95% CI, 0.4–2.4 months) compared to 11 months (95% CI, 0.7-not reached) for patients with non-malignancy related HPS (p-value:0.006; Figure). On univariableanalysis, factors associated with a worse survival were serum albumin <2 g/dL (hazard ratio, 8.3), malignancy-related HPS (hazard ratio, 7.3) and serum creatinine >1.3 mg/dL (hazard ratio, 3.8). Conclusion:In this large series of adult HPS patients treated at a single tertiary care center, most cases are secondary, and are associated with a worse survival compared to historical outcomes reported for children enrolled on the HLH-94 trial. This is likely related to a marked delay in referral to our institution, and high early mortality precluding consideration of SCT. Adult patients with malignancy- related HPS in this study had a markedly inferior outcome compared to patients with non-malignancy related HPS.Table 1Characteristic(Range) or [%]Total Number of patients50Median Age, years49 (18–87)Males33 [66]Median hemoglobin, gm/dL9 (6.2–13.7)Median total WBC (x109/L)1.8 (0.2–43.5)Median absolute neutrophil (x109/L)1.2 (0–33.6)Median platelet (x109/L)55 (6–288)Median aspartate aminotransferase (U/L)111 (10–9450)Median total bilirubin (mg/dL)1.9 (0.3–25.6)Median lactate dehydrogenase (U/L)472 (90–9290)Serum triglycerides (mg/dL)Median252 (68–831)>26514 [28]<26520 [40]Not available16 [32]Serum fibrinogen (mg/dL)Median160 (50–585)<15022 [44]>15022 [44]Not available6 [12]Serum ferritin (ng/mL)Median8400 (372–140,690)<5001 [2]501–300016 [32]>300124 [48]Not available9 [18]Table 2Etiology of Secondary HPSTotal Number of Patients = 46 (%)MalignancyTotal23 (46)T-cell lymphoma14B-cell lymphoma5Hodgkin's lymphoma1Myeloid neoplasm1Solid organ1Other (systemic histiocytosis)1InfectionTotal19 (38)Ebstein Barr virus7Cytomegalovirus3Nonspecific viral infection3Histoplasmosis3Bacterial2Blastomycosis1AutoimmuneTotal4 (8) [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Viral markers in patients with hemophagocytosis: A prospective study in a tertiary care hospital

Hemophagocytic syndrome (HPS) is a rare clinicopathological condition characterized by the activation of macrophages with prominent hemophagocytosis in bone marrow and other reticulo-endothelial systems. HPS can be familial or secondary to infections including viruses. To study the viral markers in patients with HPS. Serum samples of patients with HPS and control group were screened for anti EBV VCA IgM, and IgG, anti-Parvo B19 IgM, and anti-CMV IgM antibodies using commercially available ELISA kits and CMV and ParvoB19 DNA by polymerase chain reaction (PCR). The present prospective study reports the profile of viral markers in HPS cases from north India. Among the 14 HPS cases 43% (6/14) were positive for at least one viral marker tested, of which EBV was found to be the most prevalent (3/6: 50%) followed by parvovirus B19(2/6: 33%) and cytomegalovirus (1/6: 17%). Mortality was noted in 33% of virus associated HPS patients. Our study highlights the higher association of Epstein-Barr virus (EBV) with HPS as compared to other viruses along with higher rate of mortality in both parvovirus B 19 and EBV associated HPS.