From the Guidelines
Hemophagocytic Lymphohistiocytosis (HLH) diagnosis after Stem Cell Transplant (SCT) is defined by elevated ferritin of >10,000 ng/mL, along with at least two organ toxicities, including the presence of hemophagocytosis in bone marrow or organs, or at least grade 3 transaminitis, renal insufficiency, or pulmonary edema, as proposed in the most recent guidelines 1.
Key Diagnostic Criteria
The diagnostic criteria for HLH after SCT include:
- Elevated ferritin of >10,000 ng/mL
- At least two organ toxicities, such as:
- Hemophagocytosis in bone marrow or organs
- Grade 3 transaminitis
- Renal insufficiency
- Pulmonary edema
Clinical Presentation
Presenting symptoms related to CAR T–induced HLH may include:
- Fever
- Enlarged spleen
- Enlarged liver
- Swollen lymph nodes
- Skin rash
- Jaundice
- Lung problems such as coughing and trouble breathing
- Digestive problems such as stomach ache, vomiting, and diarrhea
- Nervous system problems such as headaches, trouble walking, vision disturbances, and weakness
Treatment
Treatment for HLH after SCT typically involves:
- Corticosteroids and IL-6 antagonist therapy for grade 3 or greater organ toxicity
- Etoposide may be used, although data in CAR T-cell therapy recipients are lacking 1
- Anakinra has been used for refractory HLH in CAR T-cell therapy recipients, although clinical efficacy is unclear 1 It is essential to note that the diagnosis and treatment of HLH after SCT can be challenging due to overlapping symptoms with other conditions, and prompt recognition and treatment are critical to improve outcomes 1.
From the Research
Hemophagocytic Lymphohistiocytosis (HLH) Criteria after Stem Cell Transplant (SCT)
The diagnosis of HLH after SCT can be challenging due to overlapping symptoms with common post-transplant complications. The following criteria have been mentioned in the studies:
- Hyperferritinemia 2, 3, 4, 5, 6
- Increased macrophage count in bone marrow 6
- Pancytopenia 2
- Hypertriglyceridemia 2
- Extensive hemophagocytosis involving the bone marrow and spleen 2
- Splenomegaly 6
- Elevated serum ferritin levels, with varying thresholds (500-10,000 μg/mL) 5
- Increased percentage of macrophages and hemophagocytes in bone marrow aspirates 6
Diagnostic Criteria
Different studies have used various diagnostic criteria, including:
- HLH-2004 guidelines 2, 4, 5
- HLH-94 guidelines 4
- H score 5
- PT-HLH criteria (hyperferritinemia and increased macrophage count in bone marrow) 6
Challenges in Diagnosis
The diagnosis of HLH after SCT is complicated by the similarity in symptoms with other post-transplant complications, such as: