Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Mar 29, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a condition called secondary hemophagocytic lymphohistiocytosis (sHLH), which is a serious immune disorder that can cause severe fevers and other health problems. The goal of the study is to better understand why some people develop this condition and how it can be diagnosed and treated. Adults aged 18 and older who have been diagnosed with sHLH are eligible to participate.

If you join the study, you will have several check-ups over a period of 9 to 12 months, either in the hospital or at an outpatient clinic. During these visits, you will have physical exams and blood tests, which may also be done by your own doctors. The blood samples will help researchers learn more about the condition. While you won’t receive new treatments specifically for this study, your healthcare team may suggest standard medications that can help. You also have the option to continue participating in follow-up visits once a year for up to three additional years. This trial is currently recruiting participants, and your involvement could contribute to important research that helps improve care for others with this condition.

Gender

ALL

Eligibility criteria

• * 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 \>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.
• • 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.