A Randomized Controlled Study of High-dose Cyclophosphamide Induction Therapy in Adult Patients With HLH

Inclusion criteria

• Age range from 18 to 65 years old (including the critical value), gender is not limited;
• According to the diagnostic criteria of HLH-2004, HLH can be diagnosed if any of the following two criteria are met:

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• Molecular diagnosis is consistent with HLH: Currently known HLH related pathogenic genes exist, such as PRF1, UNC13D, STX11, STXBP2, Rab27a, LYST, SH2D1A, BIRC4, ITK, AP3β1, MAGT1, CD27 (cluster of differentiation antigen 27 )and other pathological mutations.
• Meet 5 or more of the following 8 indicators:

• Fever: body temperature &gt; 38.5 ℃, continuous &gt; 7 d; ② Splenomegaly;

• Hemocytopenia (involving two or three peripheral blood lines) : hemoglobin &lt; 90 g/L (&lt; 4 weeks infant, hemoglobin &lt; 100 g/L), platelet &lt; 100×109/L, neutrophils &lt; 1.0×109/L and not caused by reduced hematopoietic function of bone marrow; ④ High triglyceride (TG) sepsis and/or low fibrinogenemia: triglyceride &gt; 3 mmol/L or 3 standard deviations above the same age, fibrinogen &lt; 1.5g /L or less than 3 standard deviations for the same age; (5) Hematophagy was found in bone marrow, spleen, liver or lymph nodes;

• The activity of NK cells is decreased or absent;

⑦ Serum ferritin increase: ferritin ≥500 μg/L; Elevated sCD25 (soluble interleukin-2 receptor). (3) Those who can understand the research content, agree to comply with the research plan, and voluntarily sign the informed consent.

Exclusion criteria

• HLH caused by treatable infectious causes (such as bacteria, fungi, viruses (except Epstein-Barr virus), protozoa, etc.);
• Have a history of allergy or contraindications to the drugs involved in the program;
• Organ damage caused by long-term chronic diseases;
• Extreme physical weakness, unstable vital signs and inability to tolerate large doses of cyclophosphamide;
• Severe and/or uncontrolled co-morbidivities (e.g., uncontrolled diabetes, pulmonary hypertension, etc.) that the investigator believes may pose an unacceptable safety risk or interfere with protocol compliance;
• Mental instability or history of severe mental illness
• Other factors determined by the researcher that subjects are not suitable to participate in this study.