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



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.



Median EBV-DNA concentrations before and 2 weeks after receiving the L-DEP regimen were 9.6 × 10(5) (1.5 × 10(4) - 1 × 10(9)) copies/mL and 2.2 × 10(5) (3.8 × 10(2) - 1.2 × 10(7)) 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.



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).
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Jingshi
J
Wang
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Yini
Y
Wang
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Lin
L
Wu
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Jia
J
Zhang
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Wenyuan
W
Lai
Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. zhaowww263@yahoo.com.
Zhao
Z
Wang
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000627:therapeutic use; D002648:Child; D002945:Cisplatin / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012074:Remission Induction; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D055815:Young Adult
D004279:DNA, Viral; D011092:Polyethylene Glycols; D005047:Etoposide; C042705:pegaspargase; D001215:Asparaginase; D002945:Cisplatin; D011241:Prednisone
Epstein–Barr virus; Hemophagocytic lymphohistiocytosis; PEG-aspargase