A Patient with Sequential Diseases of Langerhans Cell Sarcoma, Langerhans Cell Histiocytosis, and Acute Lymphoblastic Leukemia / 罕见病研究

Langerhans cell histiocytosis(LCH)and Langerhans cell sarcoma(LCS)are characterized by clone proliferation of Langerhans-type cells, which may occur concurrently or sequentially with T-cell acute lymphoblastic leukemia (T-ALL) and other Lymphoid neoplasms. A 15-year old female patient diagnosed with T-ALL developed LCH involving multiple systems during maintenance chemotherapy of T-AL. After treated with chemotherapy with improved result, the patient showed progression of the illness and refractory to the second-line treatment. We found c.G35A (p.G12D)mutation in the KRAS gene and used the targeted drug Trametinib for treatment. The treatment proved effective, leading to partial remission within a week. Three months after Trametinib treatment, the patient developed new lymphadenopathy. Biopsy revealed the existence of LCS. The disease progressed quickly, and the patient died 7 days after diagnosis of LCS. The case of patients with T-ALL then developing LCH and LCS sequentially is extraordinarily rare. The causes of the case is unclear and may be related to cell transdifferentiation, clonal evolution, and chemotherapy. Targeted drugs can contain this disease for a short time.

Research progress of the central nervous system leukemia in children / 中华实用儿科临床杂志

Acute leukemia (AL) is the most common tumor in childhood.With the improvement of risk stratification therapy, the complete remission rate of AL has been significantly improved.However, central nervous system leukemia (CNSL) remains the major cause of recurrence and death of leukemia.This study aims to review the pathogenesis, diagnosis and treatment of CNSL in children, hoping to further improve the understanding.

Clinical analysis of five cases with pediatric secondary hemophagocytic lymphohistiocytosis / 中华实用儿科临床杂志

Objective:To analyze the clinical manifestations, laboratory examination characteristics and treatment of secondary hemophagocytic lymphohistiocytosis (HLH) in children with different etiologies, and to further explore the stratified diagnosis and treatment of pediatric secondary HLH, in an attempt to improve pediatricians′ understanding of this disease.Methods:The clinical data of 5 children with secondary HLH treated at Beijing Children′s Hospital, Capital Medical University from January 2018 to December 2019 were retrospectively analyzed, to explore the diagnosis and subsequent treatment of the primary HLH.Results:Five patients (including 3 boys and 2 girls) had a median onset age of 1.5 (0.5-12.7) years.At the early stage of the disease, all patients had fever and hemocytopenia.After admission, HLH-related examinations were performed and secondary HLH was diagnosed.The underlying primary diseases were lymphoma, hepatitis-associated aplastic anemia, Langerhans cell histiocytosis, systemic autoinflammatory disease and hereditary metabolic disease.Except for controlling HLH activation, the treatment of primary disease was also of great significance.Conclusions:Pediatric HLH is a group of syndrome with complex underlying diseases.Therefore, pediatricians should pay more attention to the stratified diagnosis of underlying primary diseases of pediatric secondary HLH.Related laboratory tests should be performed as soon as possible to determine the etiology after HLH is diagnosed.

Progress of MICB/NKG2D signaling pathway in immune escape / 国际儿科学杂志

Natural killer group 2 member D(NKG2D) is an immune receptor expressed by NK cells that recognizes the human major histocompatibility complex class I polypetide-related chain(MIC) A/B on the cell surface.The interaction between NKG2D and MICA/B plays an important role in the immunosurveillance of viruses infection and cancers.In this article, we review the research progress of the MICB/NKG2D signaling pathway in immune escape including three parts: down-regulation of membrane-bound MICB, increase of secretory MICB, and polymorphism of MICB genes.

Spontaneous regression of optic pathway glioma in children: report of three cases and review of literature / 肿瘤研究与临床

Objective:To explore the phenomenon of spontaneous regression of optic pathway glioma in children, and to improve the understanding of optic pathway glioma.Methods:The clinical data of 3 patients with spontaneous regression of optic pathway glioma in Beijing Children's Hospital of Capital Medical University from September 2012 to June 2019 were retrospectively analyzed.Results:There were 2 girls and 1 boy among the 3 patients. The median age of onset was 4 months (3-5 months), the median age of tumor regression was 10 months (8-13 months), and the interval median time from onset to tumor regression was 5 months (4-10 months). One patient was accompanied with diencephalic syndrome, and the other was accompanied with disseminated metastasis.Conclusions:The phenomenon of spontaneous regression of optic pathway glioma mostly occurs in the early childhood. Optic pathway glioma pediatric patients complicated with diencephalic syndrome or intracranial metastasis may have the possibility of tumor regression, but spontaneous regression does not mean that the symptoms can be completely improved.

Progress of pathogenesis of chronic active Epstein-Barr virus infection / 国际儿科学杂志

Chronic active Epstein-Barr virus(CAEBV)infection belongs to EBV positive T cell or NK cell lymphoproliferative diseases, which has an insidious onset, diverse clinical manifestations, rapid progression and poor prognosis.This article mainly reviews the research progress on the pathogenesis of CAEBV from four aspects: how EBV infects T/NK cells, host genetic background, virus factors and cytokine pathway.

Analysis of five cases of hepatitis associated aplastic anemia presenting with hemophagocytic lymphohistiocytosis at onset / 中华儿科杂志

Objective@#To discuss the clinical characteristics and management approaches to hepatitis associated aplastic anemia (HAAA) presenting as hemophagocytic lymphohistiocytosis (HLH) at onset.@*Methods@#The clinical data and laboratory results of hospitalized 5 HAAA patients presenting as HLH at onset in Beijing Children′s Hospital from January 2017 to May 2019 were analyzed retrospectively.@*Results@#Among 5 cases, there were 4 males and 1 female. The age of onset was 6.0 (2.7-12.7) years. All patients presented with high fever, hepatomegaly, hepatic dysfunction (aspartate aminotransferase 1 716 (1 409-2 570) U/L, alanine aminotransferase 1 699 (937-2 540) U/L) at onset. After admission, the laboratory results showed pancytopenia (white blood cell 1.2 (0.6-6.7) ×109/L, haemoglobin 94 (65-111) g/L, blood platelet 29 (10-41) ×109/L), decreased fibrinogen (1.3 (1.1-2.5) g/L), significantly elevated triglyceride (4.0 (2.8-5.1) mmol/L), ferritin (1 766 (399-5 253) μg/L) and soluble CD25 (27 457 (9 625-44 000) ng/L). Hemophagocytosis was found in the bone marrow smears of all 5 patients. The diagnosis of acute hepatitis and HLH was confirmed. During the treatment of HLH, the blood cells remain below normal level and the further biopsy of bone marrow (iliac bone) indicated low myeloproliferation. After exclusion of congenital bone marrow failure syndromes and other pancytopenic diseases, HAAA was confirmed. After the diagnosis of HAAA, 1 patient received antithymocyte globulin (ATG) and cyclosporin treatment in our hospital, 1 patient received allogeneic stem cell transplantation (HSCT) in other hospital, 2 patients received ATG in other hospitals. Only 1 patient died of severe infection.@*Conclusions@#HAAA can present as HLH at onset. It is mainly manifested by high fever, acute severe hepatitis, pancytopenia, elevated ferritin and hemophagocytosis in the bone marrow. The diagnosis of HAAA should be considered whenever cytopenia could not completely corrected while apparent improvement of HLH and hepatitis related complications were improved after immunosuppressive therapy. ATG or HSCT treatment should be performed as soon as the diagnosis of severe or transfusion dependent aplastic anemia is confirmed.

Research progress of pathogenesis and treatment of hemophagocytic Iymphohistiocytosis / 中华实用儿科临床杂志

Hkmophagocetic sendromk,which also is callkd hkmophagocetic lemphohistiocetosis( HFH),is a rapidle progrkssivk and lifk-thrkatkning hkmatological sestkm diskasks. Thk tepical fkaturks of thk diskask is thk kxck-ssivk activation of thk inflammatore rksponsk,mainle pkrformanck that a lot of kxckssivk activation CD8+ T cklls and macrophagks filtratkd in tissuks and organs,which can produck largk amounts of cetocinks,such as intkrfkron-γ,tumor nkcrosis factor-α,intkrlkucin-6 and intkrlkucin-18,and which kvkntualle lkd to thk inflammatore cetocinks storm and tissuk damagk. Llthough,HFH is a bknign histiocetic diskask,it can progrkss quiccle,its clinical manifkstations ark divkrsk,with high mortalite ratk. In rkcknt ekars,thk rkskarch of HFH pathogknksis and trkatmknt has bkkn wkll-rk-skarchkd bkfork. Thk latkst pathogknksis and trkatmknt ark summarizkd in this articlk.

The JAK-STAT pathway and hemophagocytic syndrome / 国际儿科学杂志

Hemophagocytic syndrome (HPS),also known as hemophagocytic lymphohistiocytosis (HLH),is a syndrome with multiple clinical manifestations and severe impairment of organ function caused by abnormal activation of lymphocytes and histiocytes leading to hypercytokinemia.The pathogenesis of this disease is very complicated.So far,it can not be fully clarified.Studies have shown that activation of JAK-STAT signaling pathway can activate inflammatory factor-related gene transcription,which can cause inflammatory factor cascade reaction,and ultimately lead to the occurrence of hemophagocytic syndrome.In recent years,a series of targeted drugs for JAK-STAT pathway have been developed.A JAK1/JAK2 inhibitor,ruxolitinib,has been found to be useful in the treatment of HLH.This article reviews the mechanism of action of ruxolitinib in HLH and its clinical research results.