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

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ABSTRACT

Background: Epstein–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.

Methods: In 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.

Results: Median 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.

Conclusions: This 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).

No MeSH data available.


Survival of patients with refractory EBV-HLH (a). Relationship between the number of pretreatment EBV-DNA copies (1 × 105 copies/mL) and survival (b). Relationship between the number of pretreatment EBV-DNA copies (1 × 106 copies/mL) and survival (c). Relationship between declining multiples of EBV-DNA copies and survival after L-DEP regimen (d)
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Fig3: Survival of patients with refractory EBV-HLH (a). Relationship between the number of pretreatment EBV-DNA copies (1 × 105 copies/mL) and survival (b). Relationship between the number of pretreatment EBV-DNA copies (1 × 106 copies/mL) and survival (c). Relationship between declining multiples of EBV-DNA copies and survival after L-DEP regimen (d)

Mentions: As of 1 March 2016, 14 of the 28 study patients EBV-HLH had survived and 14 had died; thus, the mortality was 50 % and the median survival 18 weeks (range 1–40 weeks, Fig. 3a). Three of the 13 patients who achieved PR or CR and underwent subsequent allo-HSCT died from EBV-HLH recurrence or transplant-related complications (Table 2). The four patients who achieved PR but did not undergo allo-HSCT for financial reasons maintained response for 4 to 20 weeks after L-DEP and died from relapse. Three of the seven patients who relapsed before receiving allo-HSCT died, and four patients are receiving a maintenance regimen at the time of publication. Four patients who did not achieve response died within 4 weeks of the L-DEP regimen.Fig. 3


PEG-aspargase and DEP regimen combination therapy for refractory Epstein – Barr virus-associated hemophagocytic lymphohistiocytosis
Survival of patients with refractory EBV-HLH (a). Relationship between the number of pretreatment EBV-DNA copies (1 × 105 copies/mL) and survival (b). Relationship between the number of pretreatment EBV-DNA copies (1 × 106 copies/mL) and survival (c). Relationship between declining multiples of EBV-DNA copies and survival after L-DEP regimen (d)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5017041&req=5

Fig3: Survival of patients with refractory EBV-HLH (a). Relationship between the number of pretreatment EBV-DNA copies (1 × 105 copies/mL) and survival (b). Relationship between the number of pretreatment EBV-DNA copies (1 × 106 copies/mL) and survival (c). Relationship between declining multiples of EBV-DNA copies and survival after L-DEP regimen (d)
Mentions: As of 1 March 2016, 14 of the 28 study patients EBV-HLH had survived and 14 had died; thus, the mortality was 50 % and the median survival 18 weeks (range 1–40 weeks, Fig. 3a). Three of the 13 patients who achieved PR or CR and underwent subsequent allo-HSCT died from EBV-HLH recurrence or transplant-related complications (Table 2). The four patients who achieved PR but did not undergo allo-HSCT for financial reasons maintained response for 4 to 20 weeks after L-DEP and died from relapse. Three of the seven patients who relapsed before receiving allo-HSCT died, and four patients are receiving a maintenance regimen at the time of publication. Four patients who did not achieve response died within 4 weeks of the L-DEP regimen.Fig. 3

View Article: PubMed Central - PubMed

ABSTRACT

Background: Epstein–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.

Methods: In 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.

Results: Median 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.

Conclusions: This 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).

No MeSH data available.