Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 3
- 主要终点
- Identify immunologic mechanisms involved in the pathogenesis of sHLH from a variety of predisposing conditions.
研究概览
简要总结
Background:
Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by disrupted immune function. People with HLH are prone to fevers and illnesses, which can be fatal. Some people develop a genetic form of this disease (pHLH), but researchers do not understand why some other people develop a nongenetic form (sHLH). They also do not have good ways to diagnose and treat sHLH.
Objective:
To learn about sHLH and why some people get it and others do not.
Eligibility:
Adults aged 18 years and older with sHLH.
Design:
Participants will be admitted to the study based on a review of their medical records. Those who join will have at least 3 clinical evaluations over 9 to 12 months. These may occur during an inpatient hospitalization if they require medical care or in the outpatient clinic.
Participants will also have a physical exam at each visit. Up to half a cup of blood will be drawn at each visit. Participants may also have their blood drawn by their own doctors, who will send the samples to the researchers. Researchers may also contact these participants by telephone or video calls.
The blood will be used for clinical tests as well as research. No new treatments will be administered as part of this study; however, standard medications and treatments may be recommended.
Participants may opt to continue their visits once a year for 3 more years. Participants may also opt for an extra clinial evaluation 1 week after starting a new treatment.
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详细描述
Study Description:
The purpose of this multisite natural history study is to study the immunopathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH). This will include detailed longitudinal clinical and immunologic characterization of sHLH, as well as mechanistic studies evaluating inflammasome activation, cytotoxicity, and JAK-STAT signaling. Participants with sHLH will undergo clinical assessment and management along with three research blood draws with the option for additional blood draws at time points such as post-immunosuppressive treatment or treatment escalation and during longer-term follow-up. Participation may be in person or remote, with blood collected and processed locally then shipped to the NIH. Longitudinal clinical information will be recorded, and standard of care will be offered as needed.
Primary Objective:
To study the immunopathogenesis of sHLH from various etiologies including biomarkers, cellular phenotypes, and gene expression to determine mechanistic pathways that may be amenable to host-directed therapies.
Secondary Objectives:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Aged 18 years or older.
- •Established diagnosis of sHLH defined by meeting any published criteria, per Table 1:
- •Meeting the HLH-2004 criteria.
- •HScore of >
- •For those without a bone marrow biopsy to evaluate for hemophagocytosis (worth 35 points in the criteria), HScore>134 will be used.
- •For those with underlying rheumatologic disease: meeting the 2016 American College of Rheumatology criteria for macrophage activation syndrome.
- •Agree to storage and sharing of study data and biospecimens for future research use.
- •Table 1: Published Criteria for HLH
- •HLH-2004 Criteria:
- •Molecular diagnosis of HLH OR At least 5 of 8 below criteria:
- •Fever (>38.4 Degrees Celcius)
- •Splenomegaly
- •Cytopenias affecting >=2 of 3 lineages: Hgb <9 g/dL, platelets <10^5/microliter, neutrophils <10^6/microliter
- •Hypertriglyceridemia (>256 mg/dL) and/or fibrinogen <1.5 g/L
- •Hemophagocytosis on biopsy
- •Serum ferritin >=500 ng/mL
- •Increased serum sCD25 (>2400 U/mL)
- •Low or absent NK cell activity
- •Known immunosuppression:
- •0 (no) or 18 (yes)
- •Temperature (degrees, Celsius):
- •0 (<38.4), 33 (38.4-39.4), 49 (>39.4)
- •Organomegaly:
- •0 (no), 23 (liver/spleen), 38 (both)
- •Number of cytopenias:
- •0 (1 lines), 24 (2 lines), 34 (3 lines)
- •Ferritin (ng/mL):
- •0 (<2000), 35 (2000-6000), 50 (>6000)
- •Triglycerides (mg/dL):
- •0 (<1.5), 44 (1.5-4), 66 (>4)
- •Fibrinogen (g/L):
- •0 (>2.5), 30 (<2.5)
- •AST (IU/mL):
- •0 (<30), 19 (>30)
- •Hemophagocytosis:
- •0 (no) or 35 (yes)
- •Cutoff value=169
- •ACR 2016-MAS Criteria:
- •A febrile patient with known or suspected sJIA is classified as having macrophage activation syndrome if the following criteria are met:
- •Ferritin >684 ng/mL
- •AND any 2 of the following:
- •Platelets <=181,000/microliter
- •AST >48 IU/mL
- •Triglycerides >156 mg/dL
- •Fibrinogen <=3.6 g/L
- •Abbreviations: ACR, American College of Rheumatology; AST, aspartate transaminase; Hgb, hemoglobin; HLH, hemophagocytic lymphohistiocytosis; MAS, macrophage activation syndrome; NK, natural killer, sJIA, systemic juvenile idiopathic arthritis.
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Currently pregnant.
- •Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.
研究组 & 干预措施
sHLH
Hemophagocytic lymphohistiocytosis (HLH) represents a clinical condition of persistent, dysregulated immune activation with unrelenting fevers, hyperferritinemia, and cytopenias, which lead to multiorgan failure and death.
结局指标
主要结局
Identify immunologic mechanisms involved in the pathogenesis of sHLH from a variety of predisposing conditions.
时间窗: Through end of study.
To study the immunopathogenesis of sHLH from various etiologies including biomarkers, cellular phenotypes, and gene expression to determine mechanistic pathways that may be amenable to host-directed therapies.
次要结局
- Prospectively define acute and longitudinal clinical profiles that predict key clinical outcomes.(Through end of study.)
- Characterize risk factors to identify populations at risk for developing sHLH.(Through end of study.)
- Compare clinical and immune profiles between the classically defined HLH subgroups.(Through end of study.)
- Improve the understanding of the pathogenesis of sHLH.(Through end of study.)