PEG-aspargase and DEP regimen combination therapy for refractory Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis

Abstract

BackgroundEpstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is the most frequent subtype of secondary HLH triggered by infections. Previous studies have shown that ~30 % or more of patients with EBV-HLH do not respond to standard therapy. This study investigated the efficacy and safety profile of a modified DEP regimen in combination with PEG-aspargase (L-DEP) as a salvage therapy for refractory EBV-HLH.MethodsIn this study from October 2014 to October 2015, 28 patients with refractory EBV-HLH received a L-DEP regimen at the Beijing Friendship Hospital, Capital Medical University. Treatment efficacy and adverse events were evaluated at 2 and 4 weeks after L-DEP treatment.ResultsMedian EBV-DNA concentrations before and 2 weeks after receiving the L-DEP regimen were 9.6 × 105 (1.5 × 104 − 1 × 109) copies/mL and 2.2 × 105 (3.8 × 102 − 1.2 × 107) copies/mL, respectively; the post-treatment values were significantly lower than that of the pretreatment (P = 0.048). Nine of the 28 study patients achieved complete response (CR) and 15 partial response (PR), resulting in an overall response rate of 85.7 % (CR+PR). Four patients who did not achieve response died within 4 weeks of receiving L-DEP. Thirteen of the 24 patients who achieved partial or complete response received subsequent allogenic hematopoietic stem cell transplantation (allo-HSCT). Ten of these 13 patients survived until 1 March 2016. The major adverse effects of the L-DEP regimen were high serum amylase concentrations, abnormal liver function, and coagulation disorders.ConclusionsThis study suggests that L-DEP is a safe and effective salvage therapy prior to allo-HSCT for refractory EBV-HLH and increases the possibility of such patients receiving allo-HSCT. A prospective multicenter large-scale clinical trial that aims to validate the L-DEP regimen for refractory EBV-HLH is currently underway (ClinicalTrails.gov Identifier: NCT02631109).

Requirement for etoposide in the initial treatment of Epstein‐Barr virus–associated haemophagocytic lymphohistiocytosis

“…According to previous literature, age is a negative factor for the prognosis of EBV‐HLH, and adult EBV‐HLH patients suffer poorer prognoses compared to children (Tseng et al , ; Kogawa et al , ; Arca et al , ). Our centre uses L‐DEP as a salvage treatment for relapsed and refractory EBV‐HLH, which can effectively improve the remission rate and achieve the goal of bridging to allogeneic haematopoietic stem cell transplantation (allo‐HSCT) (Wang et al , ). However, some controversies remain regarding the initial treatment strategy in EBV‐HLH.…”

“…Group 2: patients whose initial therapy did not include etoposide. transplantation (allo-HSCT) (Wang et al, 2016). However, some controversies remain regarding the initial treatment strategy in EBV-HLH.…”

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in adults and adolescents—a life-threatening disease: analysis of 133 cases from a single center

“…For the patients with refractory EBV-HLH and no remission after the initial HLH-94/HLH-04 regimen and the patients with alleviation after the initial treatment but recurrent EBV-HLH, the available salvage treatments mainly include anti-thymocyte globulin (ATG) [20], tumor necrosis factor alpha (TNF-α) inhibitor [21], anti-CD52 monoclonal antibody [5,22], anti-CD20 monoclonal antibody [23,24], and DEP/L-DEP [25,26]. For the refractory or recurrent EBV-HLH, our previous study shows that the DEP and L-DEP regimens achieved a high treatment efficiency and prolonged the survival time of the patients, and enables more patients to undergo allo-HSCT [25,26]. In this study, our results also showed the very high treatment efficiency of the DEP and L-DEP regimens in the refractory EBV-HLH patients with no remission after HLH-94/ HLH-2004 and recurrent patients; and the therapeutic efficacy of L-DEP against EBV-HLH was higher than DEP.…”

Requirement for Containing Etoposide in the Initial Treatment of Lymphoma Associated Hemophagocytic Lymphohistiocytosis

“…There were 52 patients with initial etoposide and 14 without one. The baseline level between two group shows no differences (p > 0.05) ( Table 1) for DEP/L-DEP regimen once a week [13,15], 60-100 mg/m2 d1-d3 for E-CHOP regimen. .…”