DEP方案挽救治疗成人难治性噬血细胞综合征的临床研究

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

目的 观察脂质体阿霉素联合依托泊苷和大剂量甲泼尼龙（DEP）方案挽救治疗成人难治性噬血细胞综合征（HLH）患者的有效性.方法 以41例难治性HLH患者为研究对象,采用DEP方案治疗2周和4周后,参照美国中西部协作组制订的标准进行疗效评价.结果 41例患者中,男28例,女13例,中位年龄31（18～62）岁.总反应率（ORR）为78.1％（32例）,其中完全缓解（CR）率为29.3％（12例）,部分缓解（PR）率为48.8％（20例）.41例患者中有8例未找到引起HLH的原发病（CR 5例,PR2例）;其余33例患者中原发性HLH 1例（CR 1例）,淋巴瘤相关HLH 20例（CR 3例,PR 12例）,EBV相关HLH 12例（CR 3例,PR 6例）.对DEP方案无应答的9例患者均在开始挽救治疗后的2～4周内死亡;达到PR和CR的32例患者在诱导缓解后积极针对原发病治疗,包括化疗、异基因造血干细胞移植、脾脏切除等,其中20例患者病情持续缓解.结论 单臂研究结果提示,DEP方案可能是一种有效的用于成人难治性HLH患者的挽救治疗方案.

Objective To investigate the efficacy of liposomaldoxombicin together with etoposide and high dose methylprednisolone （DEP） as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis （HLH）. Methods Total 41 patients with refractory HLH were enrolled in this study. The efficacy of treatment with DEP regimen after 2 and 4 weeks were evaluated according to the United States Midwest Cooperative HLH Group. Results Of 41 refractory HLH patients, 28 were males and 13 females. The median age was 31 （18-62） years old. The overall response rate （ORR） was 78.1% （32/41）, including 12 patients （29.3%） achieved complete remission （CR） and 20 （48.8%） achieved partial remission （PR）. The underlying disease of HLH were identified in 33 patients, including 1 case of primary HLH （CR）, 20 cases of lymphoma associated HLH and 12 cases of EBV associated HLH. There were still 8 cases with unknown underlying disease. The 9 patients who had no response to DEP died within 2 to 4 weeks after salvage therapy. Twenty of the 32 patients who achieved PR or CR survived to undergo subsequent chemotherapy, allogenic hematopoietic stem cell transplantation （allo-HSCT） or splenectomy. Conclusion The single-arm study suggested that DEP regimen appeared to be an effective salvage protocol for adult patients with refractory HLH.