Evolution of diagnostic accuracy and survival rates for FHL in the HLH-94 to HLH-2024 study generations
| . | HLH-943 . | HLH-20044 HLH-2016-20215 . | HLH-20241 . | OHI8 . |
|---|---|---|---|---|
| Clinical criteria | Fever, splenomegaly | Fever, splenomegaly | Fever, splenomegaly | Fever, splenomegaly |
| Laboratory criteria | Cytopenia in ≥2 of 3 cell lines Hemoglobin <90 g/L Platelets <100 × 109/L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥2 mmol/L Fibrinogen ≤1.5 g/L | Cytopenia in ≥2 of 3 cell lines Hemoglobin <90 g/L Platelets <100 × 109 /L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥3 mmol/L Fibrinogen ≤1.5 g/L | Cytopenia in ≥2 of 3 cell lines Hemoglobin <90 g/L Platelets <100 × 109/L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥3 mmol/L Fibrinogen ≤1.5 g/L | Cytopenia in ≥2 of 3 cell lines Hemoglobin <90 g/L Platelets <100 × 109/L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥3 mmol/L Fibrinogen ≤1.5 g/L |
| Histopathologic criteria | Hemophagocytosis in spleen/bone marrow/lymph node, no evidence of malignancy | Hemophagocytosis in spleen/bone marrow/lymph node, no evidence of malignancy | Hemophagocytosis in spleen/bone marrow/lymph node, no evidence of malignancy | Hemophagocytosis in spleen/bone marrow/lymph node |
| Inflammatory criteria | Low or absent NK-cell activity, ferritin ≥500 μg/L, soluble CD25 ≥2400 U/mL | Ferritin ≥500 μg/L, soluble CD25 ≥2400 U/mL | Ferritin ≥1000 μg/L, soluble CD25 ≥3900 U/mL | |
| Overall survival | 5 years, 50% | 2004: 5 years, 59%; 2016-2021: 3 years, 79% | NA | 5 years, 10%-30%∗ |
| . | HLH-943 . | HLH-20044 HLH-2016-20215 . | HLH-20241 . | OHI8 . |
|---|---|---|---|---|
| Clinical criteria | Fever, splenomegaly | Fever, splenomegaly | Fever, splenomegaly | Fever, splenomegaly |
| Laboratory criteria | Cytopenia in ≥2 of 3 cell lines Hemoglobin <90 g/L Platelets <100 × 109/L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥2 mmol/L Fibrinogen ≤1.5 g/L | Cytopenia in ≥2 of 3 cell lines Hemoglobin <90 g/L Platelets <100 × 109 /L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥3 mmol/L Fibrinogen ≤1.5 g/L | Cytopenia in ≥2 of 3 cell lines Hemoglobin <90 g/L Platelets <100 × 109/L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥3 mmol/L Fibrinogen ≤1.5 g/L | Cytopenia in ≥2 of 3 cell lines Hemoglobin <90 g/L Platelets <100 × 109/L Neutrophils <1.0 × 109/L Hypertriglyceridemia and/or hypofibrinogenemia Fasting triglycerides ≥3 mmol/L Fibrinogen ≤1.5 g/L |
| Histopathologic criteria | Hemophagocytosis in spleen/bone marrow/lymph node, no evidence of malignancy | Hemophagocytosis in spleen/bone marrow/lymph node, no evidence of malignancy | Hemophagocytosis in spleen/bone marrow/lymph node, no evidence of malignancy | Hemophagocytosis in spleen/bone marrow/lymph node |
| Inflammatory criteria | Low or absent NK-cell activity, ferritin ≥500 μg/L, soluble CD25 ≥2400 U/mL | Ferritin ≥500 μg/L, soluble CD25 ≥2400 U/mL | Ferritin ≥1000 μg/L, soluble CD25 ≥3900 U/mL | |
| Overall survival | 5 years, 50% | 2004: 5 years, 59%; 2016-2021: 3 years, 79% | NA | 5 years, 10%-30%∗ |
The OHI for secondary, malignancy-associated HLH in adults relates to HLH-2024 through 5 of 7 positive HLH-2024 criteria. HLH-2024 is a structured case-control study to validate the diagnostic criteria.
FHL, familial hemophagocytic lymphohistiocytosis; HLH, hemophagocytic lymphohistiocytosis; NA, not applicable; NK, natural killer; OLH, optimized HLH index.
This survival estimate relates strictly to malignancy-associated HLH in adults. Other forms of the secondary type in adult patients with HLH (triggered by autoinflammatory disorders, autoimmune disorders, or infections that come with HLH) have better outcome data.