Macrophage Activation Syndrome Clinical Trial
Official title:
Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
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....
Status | Recruiting |
Enrollment | 200 |
Est. completion date | April 1, 2031 |
Est. primary completion date | October 1, 2030 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 120 Years |
Eligibility | - INCLUSION CRITERIA: - Aged 18 years or older. - Active sHLH defined by meeting any published criteria, per Table 1: - Meeting the HLH-2004 criteria. - HScore of >168. 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. - Able to provide informed consent. - 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 HScore: 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. EXCLUSION CRITERIA: 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. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Jordan MB, Allen CE, Greenberg J, Henry M, Hermiston ML, Kumar A, Hines M, Eckstein O, Ladisch S, Nichols KE, Rodriguez-Galindo C, Wistinghausen B, McClain KL. Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO). Pediatr Blood Cancer. 2019 Nov;66(11):e27929. doi: 10.1002/pbc.27929. Epub 2019 Jul 24. — View Citation
Rocco JM, Laidlaw E, Galindo F, Anderson M, Rupert A, Higgins J, Sortino O, Ortega-Villa AM, Sheikh V, Roby G, Kuriakose S, Lisco A, Manion M, Sereti I. Severe Mycobacterial Immune Reconstitution Inflammatory Syndrome (IRIS) in Advanced Human Immunodeficiency Virus (HIV) Has Features of Hemophagocytic Lymphohistiocytosis and Requires Prolonged Immune Suppression. Clin Infect Dis. 2023 Feb 8;76(3):e561-e570. doi: 10.1093/cid/ciac717. — View Citation
Rocco JM, Laidlaw E, Galindo F, Anderson M, Sortino O, Kuriakose S, Lisco A, Manion M, Sereti I. Mycobacterial Immune Reconstitution Inflammatory Syndrome in HIV is Associated With Protein-Altering Variants in Hemophagocytic Lymphohistiocytosis-Related Genes. J Infect Dis. 2023 Jul 14;228(2):111-115. doi: 10.1093/infdis/jiad059. — View Citation
Shakoory B, Geerlinks A, Wilejto M, Kernan K, Hines M, Romano M, Piskin D, Ravelli A, Sinha R, Aletaha D, Allen C, Bassiri H, Behrens EM, Carcillo J, Carl L, Chatham W, Cohen JI, Cron RQ, Drewniak E, Grom AA, Henderson LA, Horne A, Jordan MB, Nichols KE, Schulert G, Vastert S, Demirkaya E, Goldbach-Mansky R, de Benedetti F, Marsh RA, Canna SW; HLH/MAS task force. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023 Oct;82(10):1271-1285. doi: 10.1136/ard-2023-224123. Epub 2023 Jul 24. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Identify immunologic mechanisms involved in the pathogenesis of sHLH from a variety of predisposing conditions. | 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. | Through end of study. | |
Secondary | Prospectively define acute and longitudinal clinical profiles that predict key clinical outcomes. | To prospectively and longitudinally characterize the predisposing conditions, clinical features, acute triggers, clinical labs, and outcomes of a cohort of individuals meeting sHLH criteria. | Through end of study. | |
Secondary | Compare clinical and immune profiles between the classically defined HLH subgroups. | To compare biomarkers and immune profiles between the classically defined sHLH subgroups (malignancy, autoimmune, immune-therapy, infectious-triggered, unknown etiology). | Through end of study. | |
Secondary | Improve the understanding of the pathogenesis of sHLH. | To evaluate for novel immunologic subsets of sHLH with unsupervised analyses using a multi-omic approach, including single-cell transcriptomics and proteomics. | Through end of study. | |
Secondary | Characterize risk factors to identify populations at risk for developing sHLH. | To evaluate for rare, protein-altering variants in genes associated with cytotoxicity, inflammasome activation, or immunoregulation via (optional) co-enrollment in NIAID Centralized Sequencing protocol. | Through end of study. |
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