儿童EB病毒相关噬血细胞综合征的分子生物学机制和诊疗研究进展

EB病毒相关噬血细胞综合征起病凶险,进展迅速,预后差,未经治疗者病死率高.其具体发病机制目前尚不完全清楚,可能与SH2D1A基因突变和EBV潜在膜蛋白1有关.诊断首先需符合噬血细胞性淋巴组织细胞增多症诊断标准,并存在EB病毒感染证据,同时排除原发性噬血.治疗上首选联合化疗,若化疗效果不佳,可行造血干细胞移植和单克隆抗体治疗.     

血源播散性肺结核继发噬血细胞综合征1例

Hemophagocytic lymphohistiocytosis (HLH) was a life-threatening syndrome due to the uncontrolled immune activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages. HLH is characterized by primary and secondary causes, the early diagnosis and treatment of patients are closely related to the prognosis and clinical outcome of patients. The clinical presentation is variable but mostly includes prolonged fever, splenomegaly, coagulopathy, hypertriglyceridemia, and hemophagocytosis, none of them is specific and particular for HLH. Tuberculosis (TB) infection is one of the causes of HLH. HLH caused by TB is very rare clinically, but it has a high mortality. For patients with fever of unknown origin, HLH-related clinical manifestations sometimes present before the final diagnosis of TB, and HLH is associated with the most significant mortality rate. This article is mainly about a 28-year-old patient with HLH who suffered from severe TB infection. The patient attended a hospital with a history of 2 months of prolonged fever, 10 days booger and subcutaneous hemorrhage in lower limbs. Before this, he was in good health and denied any history of tuberculosis exposure. Combined with relevant laboratory test results (such as splenomegaly, hemoglobin, platelet count, and hypertriglyceridemia) and clinical manifestations (e.g. fever), the patient was diagnosed with hemophagocytic lymphohistiocytosis, but the etiology of HLH remained to be determined. To confirm the etiology, the patient was asked about the relevant medical history (intermittent low back pain) and was performed chest CT scan, bone marrow biopsy, and fundus photography. Finally, he was diagnosed with hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis. In response to this, intravenous methylprednisolone and anti-tuberculosis treatment (isoniazid, pyrazinamide, moxifloxacin, and amikacin) were administered to the patient. After more than a month of treatment, the patient recovered from HLH caused by severe TB infection. Therefore, this case suggests that we should be vigilant to the patient who admitted to the hospital with fever for unknown reasons, to diagnose HLH as early as possible and clarify its cause, then perform interventions and treatment, especially HLH secondary to tuberculosis. Also, cases of atypical TB and severe TB should be carefully monitored to achieve early diagnosis and early intervention.     

Accuracy of the criteria for hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis, also known as a hemophagocytic syndrome, is a life-threatening condition that can develop in critically ill patients with malignancies, severe infections, during chemotherapy, and may be associated with currently known or unknown genetic abnormalities; however, this list of potential causes can be extensive. The purpose of this study is to draw attention to the accuracy of its diagnostic criteria, association with a variety of clinical conditions, pathophysiological mechanisms, and outcomes of the diseases. From the medical records in our hospital, we retrospectively extracted 13 cases with hemophagocytosis over a 10-year period. Subsequently, we thoroughly analyzed medical records for the criteria used, the time required for making a diagnosis, adequacy of the criteria, management, and outcomes. We found that not all criteria were used for diagnosis, and the most sensitive and specific tests (genetic study, ferritin, and soluble IL-2r levels) were sometimes bypassed. Late diagnosis delayed management of some patients. Only a few treatment options were used for patient care. The hemophagocytic syndrome is a very rare and fatal entity requiring highly sensitive and specific diagnostic criteria for prompt diagnosis, targeted management, and thorough follow-up. Every patient admitted to the hospital with life-threatening conditions should be suspected and tested for the hemophagocytic syndrome as early as possible. The criteria for hemophagocytic lymphohistiocytosis should be revised, with the most sensitive and specific ones being done in all cases. Subsequently, each patient should be tested for the presence of genetic abnormalities that correlate with the syndrome.     

Blood and Marrow Transplant Clinical Trials Network: Progress since the State of the Science Symposium 2007

Outcomes of hematopoietic cell transplantation continue to improve. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from related and unrelated donors. In June 2007, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a State of the Science Symposium (SOSS) in Ann Arbor and identified 11 high priority clinical trials for the network to pursue. This article reviews both the status of those trials and the record of achievement of the BMT CTN as it convenes another SOSS in Grapevine, Texas in February 2014.     

Hemophagocytic lymphohistiocytosis and primary immune deficiency disorders

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled immune activation and is traditionally associated with inherited gene defects or acquired causes. In addition to abnormalities in cytotoxic granules and lysosomes, various primary immune deficiency disorders (PID) have been identified among patients suffering from HLH. Our purpose was twofold: to better characterize and detail the association between PID and HLH.