化疗联合亲缘HLA半相合淋巴细胞输注治疗难治性成人EBV相关噬血细胞综合征

Chemotherapy combined with relative HLA-haploidentical lymphocyte infusion therapy in refractory adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis

目的观察化疗联合亲缘HLA半相合淋巴细胞输注治疗难治性成人EB病毒相关噬血细胞综合征(EBV-HLH)的疗效。方法回顾性收集2017年7月至2019年7月于首都医科大学附属北京友谊医院经过噬血细胞综合征一线方案(HLH-94/HLH-04)及挽救方案(DEP/L-DEP)治疗均无效后通过化疗联合亲缘HLA半相合淋巴细胞输注治疗的16例难治性成人EBV-HLH患者的临床资料。亲缘HLA半相合淋巴细胞输注方案为:在DEP方案化疗后24 h输注亲缘HLA半相合淋巴细胞(阿霉素脂质体25 mg/m^2第一天;依托泊苷100 mg/m^2第一天;甲基强的松龙15 mg/kg第一天,淋巴细胞输注第三天)。取化疗前1天及淋巴细胞输注后3天的化验结果进行比较(包括血象、肝功能、铁蛋白、EBV-DNA拷贝数等)。结果16例在经过一线治疗及挽救治疗后仍未达到部分应答的患者中,经过化疗联合亲缘HLA半相合淋巴细胞输注后的5例患者达到了部分应答,11例患者仍为无应答。在5例达到了部分应答的患者中3例患者进行了异基因造血干细胞移植。回输后的患者血小板得到一定程度的恢复,铁蛋白和EBV-DNA的拷贝数存在下降的趋势。结论对于经过噬血细胞综合征一线方案(HLH-94/HLH-04)及挽救方案(DEP/L-DEP)治疗均无效,并且无法立即接受异基因造血干细胞移植的EBV-HLH患者,化疗联合亲缘HLA半相合淋巴细胞输注的方法可作为尝试,它可以使部分患者拥有异基因造血干细胞移植的机会,对控制疾病的进展有一定作用。

Objective To observe the efficacy of chemotherapy combined with relative HLA-haploidentical lymphocyte infusion in refractory adult Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis(EBV-HLH).Methods The clinical information of 16 refractory adult EBV-HLH patients who were treated by relative HLA-haploidentical lymphocyte infusion after the HLH first-line regimen(HLH-94/HLH-04)and salvage regimen(DEP/L-DEP)were ineffective in Beijing Friendship Hospital,Capital Medical University from July 2017 to July 2019 was collected.The relative HLA-haploidentical lymphocyte infusion regimen was:the infusion of the cells was performed at 24 hours after DEP regimen(Liposomal doxorubicin 25 mg/m^2 on the first day;Etoposide 100 mg/m^2 on the first day;Methylprednisolone 15 mg/kg on the first day,Lymphocyte infusion on the third day).The laboratory test results of 1 day before chemotherapy and 3 days after lymphocyte infusion were compared(include blood routine,liver function,ferritin,EBV-DNA copy and so on).Results Among the 16 patients who did not reach partial response(PR)after HLH first-line treatment and salvage treatment,5 patients achieved PR after chemotherapy combined with relative HLA-haploidentical lymphocyte infusion therapy,11 patients remianed unresponsive.Among the 5 patients who achieved PR,3 patients had allogeneic hematopoietic stem cell transplantation.Platelets recovered to a certain extent after lymphocyte infusion,ferritin and the copy of EBV-DNA showed a downward trend.Conclusion Chemotherapy combined with relative HLA-haploidentical lymphocyte infusion can be used as an attempt for patients who are unable to receive allogeneic hematopoietic stem cell transplantation immediately after the first-line HLH therapy(HLH-94/HLH-04)and rescue therapy(DEP/L-DEP)were ineffective.It can provide some patients with the opportunity of allogeneic hematopoietic stem cell transplantation and plays a certain role in controlling the progress of the disease.