This prospective study enrolls subjects who have clinical and laboratory manifestations related with hemophagocytic lymphohistiocytosis. The purpose of the study is to evaluate clinical and biological features of adult hemophagocytic lymphohistiocytosis. The enrolled subjects into this study will be evaluated according to the HLH (hemophagocytic lymphohistiocytosis)criteria and treated with systemic immunosuppressive therapy or chemotherapy. All subjects will be regularly monitored by physicians participating in this study.

Study process is as follows.

1. Informed consent for subjects fulfilling the inclusion criteria.

2. Laboratory evaluation will be done for subjects according to the following diagnostic criteria.

   • Diagnosis will be established if one of either 1 or 2 below is fulfilled

     1. A molecular diagnosis consistent with HLH
     2. Diagnostic criteria for HLH fulfilled (5 out of 8 criteria below)

   • fever ≥ 38.5'C for ≥ 7 days

   • splenomegaly ≥ 3 finger breadth below left subcostal margin

   • cytopenias affecting ≥2 of 3 lineages in peripheral blood (Hemoglobin < 9 g/L, Platelets < 100 × 109/L, Absolute neutrophil count < 1.0 × 109/L)

   • Hypertriglyceridemia and/or hypofibrinogenemia: Fasting triglycerides ≥ 265 mg/dL, fibrinogen ≤ 1.5 g/L

   • Hemophagocytosis in bone marrow or spleen or lymph node

   • Low or absent NK-cell activity (according to local laboratory reference)

   • Ferritin ≥ 500 mcg/L

   • Soluble CD25 (sIL-2 receptor) ≥ 2,400 U/mL

Inclusion Criteria:

• Subjects should fulfill the following criteria

  1. Subjects should have at least one of the following problems

     1. Presence of hemophagocytosis in tissue or bone marrow
     2. Presence of at least 3 conditions among 8 conditions of HLH diagnostic criteria

  2. Age > 18 years

  3. Written informed consents

     Exclusion Criteria:

• Subjects cannot satisfy the inclusion criteria

Subjects who have clinical and laboratory manifestations related with hemophagocytic lymphohistiocytosis.