Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis

Abstract

Key Points• A salvage therapy for adults with refractory hemophagocytic lymphohistiocytosis.• Liposomal doxorubicin treatment combined with etoposide and methylprednisolone showed an encouraging overall response and was welltolerated.Hemophagocytic lymphohistiocytosis (HLH) is a refractory immune disorder with a significant risk of death. Although standard therapy has dramatically improved survival in HLH patients, approximately 30%, especially adults, show no response to current treatment strategies. This prospective study aimed to investigate the efficacy of liposomal doxorubicin treatment combined with etoposide and methylprednisolone (doxorubicin-etoposidemethylprednisolone; DEP) as a salvage therapy for adult refractory HLH. Adult patients who did not achieve at least partial response 2 weeks after initial standard HLH therapy were enrolled in this study between June 2013 and June 2014. Response to salvage therapy was assessed at 2 and 4 weeks after initiation of DEP therapy and patients were followed until death or until November 2014. Sixty-three refractory HLH patients were enrolled, including 29 cases of lymphoma-associated HLH, 22 cases of Epstein-Barr virus-associated HLH, and 4 cases of familial HLH. There were 8 cases with unknown underlying diseases. Seventeen cases (27.0%) achieved complete response and 31 cases (49.2%) achieved partial response. The overall response was 76.2% (48/63). Patients who showed no response to DEP died within 4 weeks after salvage therapy. Twenty-nine of the 48 patients who achieved partial or complete response survived to subsequent chemotherapy, allogenic hematopoietic stem cell transplantation, or splenectomy. Our study suggests that DEP regimen is an effective salvage regimen for adult refractory HLH, which can prolong patient survival as we continue to understand the responsible mechanisms and bridge the gap between HLH and its underlying diseases. This study was registered in the Chinese Clinical Trials Registry Platform

Malignancy‐associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes

“…A recent report from China, described the use of combination chemotherapy with DEP (doxorubicin, etoposide, methylprednisolone) regimen as a salvage therapy for adult patients with refractory HLH. The DEP regimen showed promising results with a complete remission in 27% and partial remission in 49% of the 63 refractory HLH patients treated 23 . Furthermore, even within the pediatric population the outcomes of HLH-94 remain less than ideal with only approximately half of patients experiencing complete resolution of disease, with a significant early mortality rates 22,24,25 .…”

A consensus review on malignancy‐associated hemophagocytic lymphohistiocytosis in adults

“…Targets the cytokine storm and T-cell proliferation using etoposide (75-100 mg/m 2 ), corticosteroids, polyvalent immunoglobulins (therapeutic dosing) and, when the first hit is unsuccessful, salvage regimens such as DEP (liposomal doxorubicin, etoposide, methylprednisolone), alemtuzumab-based therapy, or cytokine adsorption using therapeutic cytokine adsorption columns or plasmapheresis 63-65 ,…”

Hemophagocytic Lymphohistiocytosis during the Postpartum Stage of Pregnancy: A Report of Eight Cases

“…After a test of NK cell activity and sCD25, the patient was diagnosed with HLH. She improved after 3 courses of a doxorubicin, etoposide, and high-dose methylprednisolone (DEP) regimen [6]. The remission did not last, as the patient started a fever again 3 months later.…”