Hemophagocytic syndrome in a patient with Fanconi anemia and VACTERL association / Síndrome hemofagocítica em paciente com anemia de Fanconi e associação VACTERL

INTRODUCTION: Hemophagocytic syndrome results from hyperactivity of histiocytes and lymphocytes, triggered by infections, mainly viral by cytomegalovirus, Epstein-Barr and herpes. Fanconi anemia (FA) is a rare genetic disease with heterogeneous symptoms common to other diseases such as VACTERL, a disease of unknown etiology in which there are several congenital malformations. The concomitance of Fanconi and VACTERL anemia occurs in 5 to 30% of FA patients. REPORT: A 14-month-old male infant was admitted to investigate fever, hepatosplenomegaly, and granulopenia. The patient was diagnosed with hemophagocytic syndrome due to hyperferritinemia, bone marrow hemophagocytosis, transaminase elevation, decreased fibrinogen, and cytomegalovirus (CMV) infection confirmed by serology and PCR. The test with mitomycin C (MMC) showed chromosomal fragility. The patient was diagnosed with a VACTERL/FA association for having a clinic and a test compatible with both FA and VACTERL. CONCLUSION: The VACTERL/FA association is seldom described, but is present in pediatric medical practice. This study presented the main clinical-laboratory aspects and reviewed the main aspects of the concurrence of this pathology.

INTRODUÇÃO: A síndrome hemofagocítica decorre da hiperatividade de histiócitos e linfócitos e é desencadeada por infeções, principalmente virais por citomegalovírus, Epstein-barr e herpes. A anemia de Fanconi (AF) é uma doença genética rara com sintomas heterogêneos em comum a outras doenças como a associação VACTERL, uma doença de etiologia desconhecida na qual existe diversas mal formações congênitas. A concomitância da anemia de Fanconi e VACTERL é descrita em 5 a 30% dos pacientes AF. RELATO: Lactente de 14 meses, sexo masculino, admitido para investigar um quadro de febre, hepatoesplenomegalia e granulopenia. Os exames laboratoriais mostraram a hiperferritemia, elevação da transaminases, medula óssea com hemofagocitose e, sorologia e PCR positivos para citomegalovírus (CMV). O paciente foi diagnosticado com síndrome hemofagocítica por citomegalovírus. Como havia também hipoplasia do polegar esquerdo, presença de hemivértebra, agenesia renal e teste positivo de fragilidades cromossômicas com mitomicina C (MMC), o paciente foi diagnosticado com associação VACTERL/AF. CONCLUSÃO: O citomegalovírus quando infecta pacientes com problemas de imunidade como AF, apresenta risco de desencadear a síndrome hemofagocítica. A associação VACTERL/AF é pouco descrita, mas presente na prática médica da pediatria. Esse estudo descreveu os principais aspectos clínicos-laboratoriais e revisou os aspectos fundamenais descritos sobre a concomitância dessas patologias.

Analysis of clinical characteristics of early death in adult patients with hemophagocytic syndrome / 白血病·淋巴瘤

Objective:To explore the clinical characteristics of early death in adult patients with hemophagocytic syndrome (HPS).Methods:The clinical data of 53 adult HPS patients in Xianning Central Hospital, Huangshi Central Hospital and Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from September 2016 to November 2021 were retrospectively analyzed, and the patients were grouped according to whether they died within 28 d after diagnosis. The clinical characteristics of the two groups were compared. A multivariate analysis of patients' death within 28 d was performed using logistic regression.Results:In 53 adult HPS patients, the mortality rate within 28 d was 28.3% (15/53). The survival time of patients was related to white blood cell count ( r = 0.324, P = 0.018), total bilirubin level ( r = -0.280, P = 0.042) and albumin level ( r = 0.281, P = 0.042), but there was no linear causality (all P > 0.05). When compared between the death within 28 d group and the non-death within 28 d group, the differences in patients' age, platelet count, albumin level, creatine kinase isoenzyme level, triacylglycerol level, ferritin level, and central nervous system involvement were statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that platelet count <30×10 9/L, albumin <30 g/L, central nervous system involvement, and ferritin ≥10 000 ng/ml were independent risk factors for patients' death within 28 d (all P < 0.05). Conclusions:In adult HPS patients, assessing the risk of early death based on ferritin level, platelet count, albumin level, and neurological symptoms, actively correcting internal environmental disturbances, and enhancing organ support therapy can contribute to survival benefit.

Clinical analysis of seven cases of hemophagocytic lymphohistiocytosis secondary to cutaneous T-cell lymphoma / 中华皮肤科杂志

Objective:To investigate clinical and laboratory characteristics of secondary hemophagocytic lymphohistiocytosis (sHLH) associated with secondary cutaneous T-cell lymphoma (CTCL) .Methods:CTCL patients with clinically suspected sHLH were collected from Department of Hematology, Wuhan No.1 Hospital from January 2016 to October 2021, and were evaluated according to the HLH-2004 diagnostic criteria and HScore.Results:Seven CTCL patients were confirmedly diagnosed with sHLH, including 2 with primary cutaneous γδT-cell lymphoma (PC-GDTCL) , 3 with cutaneous extranodal natural killer/T-cell lymphoma (C-ENKTCL) , and 2 with primary cutaneous anaplastic large cell lymphoma (PC-ALCL) . All the 7 patients received chemotherapy, but 6 died finally, and the median overall survival duration was 26.5 days (range: 14 - 60 days) after the confirmed diagnosis of CTCL complicated by sHLH. HLH-related gene mutations, which were located in the PRF1 and LYST genes, were identified in 2 patients; lymphoma-related gene mutations were identified in the KRAS and KMT2D genes in 1 PC-GDTCL patient,and in the JAK3 and SAMHD1 genes in another PC-GDTCL patient.Conclusions:CTCL complicated by sHLH usually progresses rapidly, so early diagnosis and treatment are needed. Bone marrow biopsy and mutation screening of lymphoma- and HLH-related genes at initial diagnosis and during disease progression may facilitate early diagnosis.

Recommendations for the diagnosis and treatment of rheumatic diseases-related hemophagocytic syndrome in China / 中华内科杂志

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians′ understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.

Epidemiological characteristics and clinical features of visceral leishmaniasis in 41 children / 中华传染病杂志

Objective:To investigate the epidemiological and clinical characteristics of visceral leishmaniasis (VL) in children, and to analyze the distinguishing features of VL associated hemophagocytic lymphohistiocytosis (HLH), so that to provide reference for the diagnosis and treatment of VL.Methods:Forty-one children with VL admitted to Xi′an Children′s Hospital from July 2012 to June 2021 were enrolled. The clinical data were retrospectively analyzed, including epidemiology, clinical manifestations, laboratory data, diagnostic methods, treatment regimens and outcomes. The patients were divided into VL group and VL+ HLH group according to whether combined with HLH or not, and the clinical characteristics and laboratory findings of the two groups were compared. Two independent samples t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:Forty-one children with VL were from different provinces, including Shaanxi Province (70.73%(29/41)), Gansu Province (14.63%(6/41)), Shanxi Province (12.20%(5/41)) and Ningxia Hui Autonomous Region (2.44%(1/41)), and 87.80%(36/41) of them lived in rural areas. The peak age was >1.0 to 3.0 years old (63.41%(26/41)). They were sporadic throughout the year. The main clinical manifestations included fever (97.56%(40/41)), splenomegaly (95.12%(39/41)), lymphadenopathy (82.93%(34/41)) and hepatomegaly (60.98%(25/41)). The numbers of cases that Leishman-Donovan bodies were detected in the first, second and third bone marrow smears were 36, four and one, respectively. Anemia, thrombocytopenia and leukopenia detected by blood routine test were 100.00%(41/41), 78.05%(32/41) and 58.54%(24/41), respectively. There were statistically significant differences in the platelet count, lactate dehydrogenase, alanine aminotransferase, triglycerides, fibrinogen and ferritin between VL group (28 cases) and VL+ HLH group (13 cases) ( t=-2.56, t=2.64, Z=-2.66, t=7.15, t=-5.76 and t=3.86, respectively, all P<0.050). The proportions of hepatomegaly and hemophagocytes found in the bone marrow smears in VL group were both lower than those in VL+ HLH group, and the differences were both statistically significant ( χ2=4.47 and 10.93, respectively, both P<0.050). Twelve cases with VL+ HLH were treated with antimony (for six days) and intravenous immunoglobulin, and the others were treated with antimony only. The cure rates of the patients treated with antimony for one and two courses were 92.68%(38/41) and 4.88%(2/41), respectively. The dose of antimony was increased one third and treatment course was prolonged to eight days in one cured case. After (41.36±31.49) months of follow-up, three cases recurred after five to eight months of cure and all of them were cured after one more course of treatment with antimony. Conclusions:Children with VL are mainly distributed in rural areas. The common clinical manifestations are fever and involvement of reticuloendothelial system, which are not specific. The positive rate of Leishman-Donovan bodies found in bone marrow smears is high, and a few negative cases need repeated bone marrow aspiration. Standardized treatment with antimony for VL in children is effective, and combination therapy with immunoglobulin can be considered if patients with VL associated HLH. Very few cases may recur and antimony is still effective.

Progress in treatment of lymphoma-associated hemophagocytic syndrome / 白血病·淋巴瘤

Lymphoma-associated hemophagocytic syndrome (LAHS) accounts for a large proportion of secondary hemophagocytic syndrome (HPS) and has a poor prognosis. LAHS can be divided into two categories: HPS combined with chemotherapy and lymphoma-induced HPS. The key to the treatment of HPS combined with chemotherapy is to control the infection. While the treatment of lymphoma-induced HPS is complicated, there are new strategies in addition to traditional methods. Timely and appropriate treatment can significantly improve the short-term and long-term prognosis of patients. This article summarizes the progress in treatment of LAHS.

Adult primary hemophagocytic syndrome: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and therapeutic effect of adult primary hemophagocytic syndrome (HPS).Methods:The clinical data of a patient with primary HPS in the Third Affiliated Hospital of Southern Medical University in July 2017 were retrospectively analyzed, and the related literature was reviewed.Results:The patient was a 53-year-old female without history of basic disease, presenting as repeated high fever, with mutation of STXBP2 (FHL5), and was diagnosed as HPS according to hemophagocytic lymphohistiocytosis (HLH)-2004 criteria. The patient was treated with HLH-2004 regimen, and the efficacy was good. The patient was followed up until May 2021, and the overall survival time was 45 months.Conclusions:The atypical primary HPS and delayed primary HPS are rare, with mild clinical symptoms and only manifested by repeated high fever. Therefore, the gene mutations associated with HPS should be detected as soon as possible to confirm the diagnosis and to treat the disease early.

Hemophagocytic syndrome as the first presentation of histiocytic necrotizing lymphadenitis: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the diagnosis and treatment of histiocytic necrotizing lymphadenitis (HNL) complicated with hemophagocytic syndrome (HPS).Methods:The clinical characteristics, diagnosis, treatment process, and therapy response of a patient with HNL complicated with HPS admitted to the Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences in March 2019 were retrospectively analyzed, and the literature was reviewed.Results:This 17-year-old female patient had fever with bilateral cervical lymphadenopathy as the first presentation, accompanied by cough and expectoration. After admission, the disease progressed rapidly, and the serum ferritin increased progressively.The regimen of hormone and etoposide was used to control the disease condition. The bone marrow smear revealed atypical lymphocytes and hemophagocytic phenomenon, and the pathological features of HNL in lymph node biopsy were observed. This patient was finally diagnosed as HNL complicated with HPS. The patient's condition was stable at 3-month follow-up after discharge.Conclusions:The clinical manifestations of HNL patients complicated with HPS are similar to other hematologic malignant diseases, and application of multiple laboratory and pathological examination methods can help with early diagnosis. In the event of a progressive rise in serum ferritin, timely application of hormone therapy combined with etoposide if necessary can rapidly control the progression of the disease.

Gain-of-function STAT1 mutation and visceral leishmaniasis

ABSTRACT Gain-of-function mutations in the STAT1 gene have been initially associated with chronic mucocutaneous candidiasis. However, further research has shown that STAT1 GOF variants may increase susceptibility to infection by other intracellular pathogens. This report describes the first case of disseminated leishmaniasis associated with a STAT1 GOF mutation in a pediatric patient who did not have chronic mucocutaneous candidiasis. The patient was a four-year-old boy presenting with fever, severe asthenia, hepatosplenomegaly, pancytopenia, and liver failure. Bone marrow aspirate revealed hemophagocytosis and Leishmania parasites. Treatment consisted primarily of liposomal amphotericin B, as per the Hemophagocytic Lymphohistiocytosis 2004 protocol. After eight weeks of treatment, the patient did not improve and was submitted to diagnostic splenectomy. Activated macrophages and nodular spleen necrosis secondary to the visceral leishmaniasis were detected. Unfortunately, the patient died in the second week after splenectomy due to overwhelming systemic infection. DNA sequencing revealed a pathogenic (p. R274Q) GOF mutation in STAT1.

Herpes simplex virus-1 triggered hemophagocytic lymphohistiocytosis in a patient with granulomatosis with polyangiitis

ABSTRACT Hemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive hyperinflammatory syndrome in which an inciting event triggers massive, uninhibited activation of T lymphocytes and macrophages. Although viral infections are the most common trigger of HLH, cases of HSV-1 induced HLH are rare in adults. We present the case and postmortem findings of a 27-year-old woman diagnosed with HLH in the setting of immunosuppression for the treatment of granulomatosis with polyangiitis (GPA). Autopsy revealed evidence of herpes simplex virus-1 (HSV-1) infection and no findings suggestive of GPA recurrence.

The clinical characteristic of ocular findings secondary to hemophagocytic lymphohistiocytosis / 中国医师杂志

Objective:To describe the characterization of ocular changes secondary to hemophagocytic lymphohistiocytosis (HLH).Methods:The clinical data of 5 patients with HLH complicated with ocular involvement treated in Beijing Friendship Hospital Affiliated to Capital Medical University from September 2020 to May 2021 were retrospectively analyzed, the patients′ systemic examination and treatment were sorted out, and the ocular examination results were analyzed. The relevant literatures on ocular involvement of HLH patients were searched in China National Knowledge Infrastructure (CNKI), Pubmed, WOS, Embase and Medicine databases to summarize the characteristic manifestations of ocular involvement of HLH.Results:Of the 5 patients, 1 had primary HLH, 3 were Epstein-Barr virus-associated HLH (EBV-HLH), and 1 had diffuse large B-cell lymphoma-associated HLH. 4 patients showed unilateral or bilateral focal retinal hemorrhage and exudates. 1 male patient performed bilateral retinal pigment epithelial detachment. The literature search results showed that a total of 1 paper on ocular involvement in HLH patients was retrieved from the Chinese database and 11 papers were retrieved from the foreign database. HLH mainly involved the optic nerve, retina and choroid.Conclusions:The ocular involvement of HLH is easy to be missed or misdiagnosed because of its occult onset and complex and diverse clinical manifestations. Early examination and effective treatment may save vision and avoid missing the opportunity of systemic treatment.

Hemophagocytic lymphohistiocytosis presenting as acute coronary syndrome

Acquired Hemophagocytic Lymphohistiocytosis is a rare and deadly syndrome resulting from an overactive immune system, with uncontrolled activation of macrophages and lymphocytes, hypercytokinemia, and systemic inflammatory response. A 75-year-old male presented with typical anginal pain and was diagnosed with the acute coronary syndrome, which required a percutaneous transluminal coronary angioplasty. Instead of resolving the symptoms, the patient began to exhibit pyrexia and worsening altered sensorium with progressing renal failure, anemia, thrombocytopenia and respiratory failure. This constellation of symptoms caused the patient to require mechanical ventilation and hemodialysis. Upon laboratory analysis, hyperferritinemia provided an indication to the diagnosis of acquired hemophagocytic lymphohistiocytosis. After the initiation of dexamethasone, the patient made a significant recovery and was discharged from the hospital.

An autopsy series of an oft-missed ante-mortem diagnosis: hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal syndrome resulting from a hyperactivated immune system. Diverse patient profiles and clinical presentations often result in misdiagnosis. This article describes the varied clinical presentations and autopsy findings in three patients with this entity. The etiopathogenesis of HLH, its disparate and confounding clinical features, the diagnostic criteria, and management principles are also briefly reviewed.

Fetal familial hemophagocytic lymphohistiocytosis: a case report and literature review / 中华围产医学杂志

Objective:To discuss the clinical characteristics and genetic diagnosis of fetal familial hemophagocytic lymphohistiocytosis (FHL).Methods:Clinical data of a case of fetal FHL from Children's Hospital, Capital Institute of Pediatrics was analyzed, and related FHL cases at home and abroad were retrieved from PubMed, CNKI, and Wanfang databases using terms including "fetus", "neonate", and "familial hemophagocytic lymphohistiocytosis", from the establishment of the database to January 3, 2021, to summarize the characteristics of this disease.Results:This index case was found with fetal splenomegaly, free fluid in the abdominal cavity, and enlargement of the ventricle at 39 +3 weeks of gestation, and presented with fever, tachypnea, hepatosplenomegaly, skin ecchymosis and petechia, and lymphadenectasis after birth. Laboratory examination revealed pancytopenia, abnormal liver function, elevated ferritin and triglyceride, and decreased fibrinogen levels. CD107a excitation experiment showed decreased degranulation function of NK cell (ΔCD107a<5%). Hemophagocytosis was observed in the bone marrow smear. Genomic DNA sequence analysis demonstrated compound heterozygous mutations of c.118-308C>T and c.3002T>C in the UNC13D gene. All the above findings led to the diagnosis of FHL3. Despite chemotherapy with dexamethasone and cyclosporin, and symptomatic treatment after admission without hematopoietic stem cell transplantation, the baby died on day 52. A total of 15 papers related to fetal FHL, including 20 infants, were retrieved. Among these 21 cases (including the index case), the main clinical symptoms were fetal edema and hepatosplenomegaly, which may be accompanied by fetal distress and increased amniotic fluid volume, and postnatal fever, dyspnea, rash, and central nervous system involvement. Laboratory and imaging examination results were consistent with the diagnostic criteria for hemophagocytic hyperplasia. As far as we know, the reported fetal FHL gene mutations were PRF1 (FHL2) and UNC13D gene mutation (FHL3), in which reduced expression of perforin and granzyme can be detected, respectively. Dexamethasone, cyclosporin, etoposide, and other chemotherapy and symptomatic treatment are the primary treatments currently, and alternative therapies include intrauterine chemotherapy in the third trimester and postnatal hematopoietic stem cell transplantation. Among the 21 cases, including the index case, intrauterine death occurred in four cases, 13 children died at different times after birth, and only four children survived, among which the eldest one was 12 years old. Conclusions:FHL is a condition with atypical early signs, high mortality rate and treatment difficulties. Fetal FHL should be considered in differential diagnosis in fetuses with edema or hepatosplenomegaly besides hemolysis, infection, autoimmune diseases, and hereditary problems. Therefore, with immunotechnology and gene sequencing, early diagnosis and treatment can be prompted to improve the prognosis of this group of population.

Analysis of clinical data of 3 cases of hemophagocytic syndrome and literature review / 中国基层医药

Objective:To analyze the clinical characteristics, diagnosis, treatment and prognosis of three children with hemophagocytic syndrome (HPS) and provide diagnosis and treatment clues for reasonable treatment and prevention of serious complications and reduction of misdiagnosis and mistreatment.Methods:The clinical data of three children with HPS who received treatment in Taiyuan Maternal and Child Health Care Hospital from March 2018 to March 2020 were retrospectively analyzed. Related literature was retrieved. The clinical data of the three children were summarized to analyze the outcomes.Results:Fever (≥ 39 ℃) was the first symptom in all three cases. In the end, red blood cell line, white blood cell line, and platelet line were reduced to different degrees in all three cases. Hepatosplenomegaly was found in two cases. Transaminase highly increased in two cases, and slightly increased in one case. Ferritin greatly increased, fibrinogen decreased, and hypertriglyceridemia did not occur in all three cases. Two cases had skin rash during fever. Skin rash appeared late in one of them.All three cases had different degrees of lymphadenopathy. Bone puncture examination showed reticulocyte phagocytosis in bone marrow in one case and leishmania in bone marrow smear in another case. These two cases were cured and discharged. One case died of multiple organ failure due to rapid disease progression, and adrenal masses were found at autopsy.Conclusion:HPS has diverse clinical manifestations, complex etiology and different clinical prognoses. HPS should be considered in case of unexplained fever with hemocytopenia. The medical history and living history should be inquired in detail and relevant auxiliary examinations should be improved as soon as possible.

Progress of treatment-related hemophagocytic syndrome / 白血病·淋巴瘤

Hemophagocytic syndrome (HPS) is a rare, life-threatening inflammatory response syndrome characterized by overactivation of the immune system, which leads to organ damage. Secondary HPS is usually triggered by infection, tumor and autoimmune disease. It has been clinically found that many HPS-like manifestations also occur during drug therapy. This article reviews the related progress of HPS induced by immune checkpoint inhibitors, ibrutinib and lamotrigine, in order to provide a guidance for clinical practice.

Subcutaneous panniculitis-like T-cell lymphoma secondary to familial hemophagocytic syndrome: report of one case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics and gene mutations of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) secondary to familial hemophagocytic syndrome (FHL).Methods:The clinical features, disease evolution, gene mutation and genetic characteristics of 1 SPTCL patient secondary to FHL in Henan Children's Hospital in June 2012 were analyzed retrospectively, and the related literatures were reviewed.Results:The UNC13D of FHL patient was homozygous mutation accompanied by STXBP2 heterozygous mutation, while that of his parents and elder brother was heterozygous mutation. After regular chemotherapy with HLH-2004 regimen, the disease relapsed 4 years later, and secondary SPTCL developed after 1 year of remission with the second chemotherapy. After giving SMILE regimen chemotherapy, allogeneic hematopoietic stem cell transplantation was performed, and now the patient had disease-free survival.Conclusions:The detection of related genes in children with hemophagocytic syndrome should be improved in time to confirm the diagnosis of primary disease. FHL can follow SPTCL, and chemotherapy combined with allogeneic hematopoietic stem cell transplantation can be the only method to cure this disease.

Clinical features and therapeutic efficacy analysis of Epstein-Barr virus-positive T-cell lymphoma patients with hemophagocytic syndrome / 白血病·淋巴瘤

Objective:To investigate the effects of hemophagocytic syndrome also known as hemophagocytic lymphohistiocytosis (HLH) on the clinical features and therapeutic efficacy of patients with Epstein-Barr virus-positive T-cell lymphoma (EBV-TCL).Methods:The clinical data of patients with EBV-TCL diagnosed by pathological examination in the First Affiliated Hospital of Guangzhou Medical University from November 2015 to August 2020 were retrospectively analyzed. According to whether they were accompanied with HLH at the time of onset, patients were divided into HLH group (10 cases) and non-HLH group (13 cases), and the clinical features and prognosis of the two groups were compared. The curative effects of different treatment methods and patients with different plasma EBV-DNA titers were compared.Results:Among 23 patients, 3 cases (13.0%) were in Ann Arbor stage Ⅰ-Ⅱ, 20 cases (87.0%) were in stage Ⅲ-Ⅳ; the International Prognostic Index (IPI) score was 1 point in 3 cases (13.0%), 2 points in 4 cases (17.4%), 3 points in 8 cases (34.8%), 4 points in 8 cases (34.8%). In the HLH group, there were 2 cases of aggressive NK-cell leukemia and 3 cases of childhood systemic EBV-TCL. There were no cases of above two pathological types in the non-HLH group. In the HLH group, the proportions of patients with fever, bone marrow invasion, IPI score > 2 points, and EBV-DNA > 10 4 copies/ml were higher than those in the non-HLH group (all P < 0.05). The objective response rate (complete remission plus partial remission) of all patients after chemotherapy was 47.8% (11/23); there were 3 cases undergoing hematopoietic stem cell transplantation in both the HLH group and the non-HLH group, and all achieved objective remission. The objective remission of 7 patients and 10 patients who did not undergo hematopoietic stem cell transplantation in the HLH group and non-HLH group after lymphoma chemotherapy had 0 case and 5 cases, respectively, and the difference was statistically significant ( P = 0.044). In the chemotherapy alone group, 5 of 17 patients had objective remission, 6 patients in the chemotherapy plus transplantation group had objective remission, and the difference was statistically significant ( P = 0.039). Among 16 patients whose plasma EBV-DNA titers turned negative, 11 patients had objective remission, and 7 patients whose plasma EBV-DNA titers were continuously positive had no objective remission, and the difference was statistically significant ( P = 0.001). The 1-year overall survival rate of all patients was 69.3%, and the 2-year overall survival rate was 52.0%. In the HLH group, the 1-year and 2-year overall survival rates of 7 patients receiving chemotherapy alone and 3 patients receiving chemotherapy plus transplantation were 42.9% and 66.7%, respectively. In the non-HLH group, the 1-year overall survival rates of 10 patients receiving chemotherapy alone and 3 patients receiving chemotherapy plus transplantation were 80.0% and 100.0%, respectively; the 2-year overall survival rates were 26.7% and 100.0%,respectively. The overall survival of patients receiving chemotherapy plus transplantation was better than that of those receiving chemotherapy alone in both the HLH group and the non-HLH group, and differences were statistically significant (all P < 0.05). Conclusions:The general clinical stage of patients with EBV-TCL is later, and the prognosis of EBV-TCL patients with HLH is worse. The therapeutic efficacy may be related to plasma EBV-DNA titers. Hematopoietic stem cell transplantation can improve the remission rate.

Clinical prognosis of lymphoma-associated hemophagocytic syndrome in adults: a multicenter study / 白血病·淋巴瘤

Objective:To explore the prognostic influencing factors of adult lymphoma-associated hemophagocytic syndrome (LAHS) based on multicenter data.Methods:The clinical data of 86 LAHS patients diagnosed in 9 medical centers of Huaihai Lymphoma Working Group from January 2015 to August 2020 were retrospectively analyzed. The optimal cut-off value of continuous variables was obtained based on MaxStat algorithm. Cox proportional hazard regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used for survival analysis, and log-rank test was performed.Results:Among the 86 adult LAHS patients, 50 (58.1%) were males and 36 (41.9%) were females, the median age of the patients was 57 years old (19-76 years old), and the median overall survival (OS) time was 1.67 months (95% CI 0.09- 3.24 months). The most common pathologic type was diffuse large B-cell lymphoma (58 cases, 67.44%). Based on MaxStat algorithm, the optimal cut-off values of age, albumin, serum creatinine, lactate dehydrogenase, fibrinogen and platelet count were 64 years old, 30.1 g/L, 67 μmol/L, 1 045 U/L, 4.58 g/L and 72×10 9/L, respectively. Multivariate analysis showed that patient's age, lactate dehydrogenase, albumin and fibrinogen levels were independent influencing factors for OS (all P < 0.05). Conclusions:LAHS is dangerous and progresses quickly. Patients with age ≥ 64 years old, lactate dehydrogenase ≥ 1 045 U/L, fibrinogen ≥ 4.58 g/L and albumin < 30.1 g/L have poor survival.