Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. Current standard therapy increased the complete remission (CR) rate to more than 50%. Even so, about 30% patients fail the standard treatment. This study aimed to investigate the efficacy of liposomal doxorubicin together with etoposide, and high dose methylprednisolone (DEP) as a salvage therapy for adult refractory HLH.

Methods: Refractory HLH was defined as patient who did not achieve at least partial remission (PR) 2 weeks after initial standard HLH therapy. The DEP regimen included liposomal doxorubicin 25mg/m2 d1, etoposide 100mg/m2 Qw and methylprednisolone 15mg/kg d1-3, 2mg/kg d4-6, 1mg/kg d7-10,0.75mg/kg d11-14. We estimated the curative effect after 2 weeks therapy and 4 weeks therapy.

Results: We observed 63 refractory HLH patients from Jun 2013 to Jun 2014, including 42 males and 21 females. All the data were gathered from Beijing Friendship Hospital, 307 Hospital of PLA, Peking University People’s Hospital, Peking University Third Hospital, Beijing Chao-Yang Hospital, and Navy General Hospital. The median age was 34 years old (Range 18-78). Seventeen patients (27.0%) achieved CR and 31 patients (49.2%) achieved PR. The overall response reached 76.2% (48/63). The underlying disease of HLH were diagnosed within 2 to 8 weeks after HLH diagnosis, including 29 cases of lymphoma associated HLH, 22 cases of EBV associated HLH and 4 cases of familial HLH. There were still 8 cases had unknown underlying disease. The patients who had no response to DEP were died within 2 to 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved PR or CR survived to undergo subsequent chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HCT) or splenectomy. There were significant improvements on leukocytes, ferritin and soluble CD25 (sCD25) after 2 weeks therapy. Thrombocytes and glutamic-pyruvic transaminase (GPT) had improvements after 4 weeks therapy.

Conclusion: DEP regimen appears to be an effective salvage protocol for refractory HLH. Prospective randomized controlled trials of DEP regimen will further estimated the curative effect and define optimal dosing levels and schedules.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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