Modified DEP Regimens for the Treatment of Hemophagocytic Lymphohistiocytosis

In the investigators' previous clinical practice, it has been found that under the condition of combined treatment with safer inflammatory factors such as ruxolitinib and CCRT, further reducing the dosage of high-dose hormones and shortening the duration of use can effectively reduce the occurrence of adverse reactions while still achieving the effect of effectively alleviating HLH. This study is a prospective clinical study aimed at observing the effectiveness and safety of the modified DEP regimen in the treatment of active HLH.

Inclusion criteria

• According to the HLH-2004 criteria, the patient meets the HLH diagnosis.
• 1 year old < age < 70 years old, regardless of gender.
• Before the start of the study, total bilirubin ≤ 10 times the upper limit of normal; serum creatinine ≤ 1.5 times the normal value; fibrinogen can be corrected to ≥ 0.6g/L after infusion.

• Serum HIV antibody negative; HCV antibody negative, or HCV antibody positive, but HCV-RNA negative. HBV surface antigen and HBV core antibody are both negative. If any of the above is positive, peripheral blood hepatitis B virus DNA titer detection is required, and it must be less than 1×103 copies/ml before enrollment.

• Women of childbearing age must be confirmed to be non-pregnant through pregnancy tests, and are willing to take effective contraceptive measures during the trial and within ≥ 6 months after the last dose; pregnant and lactating women cannot participate; all male subjects take contraceptive measures during the trial and within ≥ 3 months after the last dose.

• Sign the informed consent form.

Exclusion criteria

• Allergic to liposome doxorubicin, etoposide, and ruxolitinib or with severe allergic constitution;
• Severe myocardial damage, with myocardial enzyme CK and CK-MB increased more than 3 times ULN (upper limit of normal value).
• Patients with heart disease of grade II or above (including grade II) according to the New York Heart Association (NYHA) score.
• Subjects who have used a total cumulative dose of doxorubicin ≥300mg/m2 or a total cumulative dose of epirubicin ≥450mg/m2, or who have previously used anthracyclines to cause heart disease.
• Subjects with severe mental illness;
• Severe and uncontrollable infections, such as lung infection, intestinal infection, and sepsis.
• Active massive bleeding in visceral organs (including gastrointestinal bleeding, alveolar bleeding, intracranial bleeding, etc.);
• Patients who are unable to rely during the trial and/or follow-up stage and who are participating in other clinical studies at the same time.

• For patients who intend to use PD-1 monoclonal antibodies, if the patient has any of the following conditions, PD-1 monoclonal antibodies will not be used, and only the DEP regimen that does not contain PD-1 monoclonal antibodies will be used:

• Those who are allergic to PD-1 monoclonal antibody components.
• Abnormal thyroid function.
• Those who have other severe immune reaction tendencies, including immune myocardial injury, immune hepatitis, immune pneumonia, etc.