Zheng Yong-Zhi, Zheng Hao, Li Jian, LE Shao-Hua, Hua Xue-Ling, Chen Zai-Sheng, Zheng Ling, Li Mei, Chen Yi-Qiao, Gao Qin-Li, Yang Jing-Hui, Hu Jian-Da
Department of Hematology, Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fuzhou 350001, Fujian Province, China.
Department of Hematology, Fujian Medical University Union Hospital, Fujian Institute of Hematology, Fuzhou 350001, Fujian Province, China. E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1764-1770. doi: 10.7534/j.issn.1009-2137.2016.06.027.
To study the clinical features, treatment and prognosis of patients with NK/T cell lymphoma-associated hemophagocytic syndrome(NK/T-LAHPS).
Retrospective analysis was used to explore the clinical data of 6 children with NK/T-LAHPS who were admitted in Department of Pediatric Hematology of Fujian Medical University Union Hospital from July 2012 to June 2016. The 6 patients included 4 boys and 2 girls, with a median age of 4 years(range 1.75 to 11). In 4 patients the hemophagocytic syndrome(HPS) occurred as the main primary manifestations of underlying lymphoma, in the other 2 patients HPS occurred during lymphoma progression. The clinical manifestations included persistent fever(6/6), hepatomegaly(6/6), splenomegaly(6/6) and pancytopenia(6/6). Laboratory data indicated that the level of ferritin(2179-15000 ng/ml) , LDH(608-3899 IU/L) and EBV-DNA(>10 copies/ml ) was elevated obviously. The other common clinical features of NK/T-LAHPS were hypoproteinemia(6/6), hepatic dysfunction(5/6), hypofibrinogenimia(5/6), hypertriglyceridemia(3) and hemophagocytosis in bone marrow(5/6).
After being treated according to the HLH-2004 protocol combined with supported therapy for 1 or 2 weeks, all the patients achieved a clinical response, and the laboratory indicators of HPS were improved. The combined chemotherapy of SMILE was given to 4 patients timely, among them 2 patients achieved complete remission(CR) and long term survival, 1 patient achieved partial remission(PR) and died of relapse after drug withdrawal and 1 patient died of aggravated lymphoma. The other 2 patients did not receive chemotherapy in time, HPS relapsed quickly, because of the progression of lymphoma, and all died of severe hepatic dysfunction and coagulopathy.
The NK/T-LAHPS is an invariably fatal disease with poor prognosis, and typically occurrs at the advanced stage or the terminal phase of the disease. HLH-2004- based protocol in combination with comprehensive therapy is hopeful for the patients with NK/T-LAHPS, which may delay the disease progression and provide opportunities for the treatment of primary disease. Once the laboratory indicators of HPS are improved, it is important to treat lymphoma timely with the combined chemotherapy of SMILE, which is significant for improving the prognosis.
探讨自然杀伤/ T细胞淋巴瘤相关噬血细胞综合征（NK/T-LAHPS）患者的临床特征、治疗及预后。
采用回顾性分析方法，对2012年7月至2016年6月福建医科大学附属协和医院儿科收治的6例NK/T-LAHPS患儿的临床资料进行分析。6例患儿中男4例，女2例，中位年龄4岁（1.75～11岁）。4例以噬血细胞综合征（HPS）为潜在淋巴瘤的主要首发表现，另2例在淋巴瘤进展过程中出现HPS。临床表现包括持续发热（6/6）、肝大（6/6）、脾大（6/6）和全血细胞减少（6/6）。实验室检查显示铁蛋白水平（2179～15000 ng/ml）、乳酸脱氢酶（LDH，608～3899 IU/L）及EBV-DNA（>10拷贝/ml）明显升高。NK/T-LAHPS的其他常见临床特征为低蛋白血症（6/6）、肝功能不全（5/6）、纤维蛋白原减少（5/6）、高甘油三酯血症（3例）及骨髓噬血细胞现象（5/6）。
按照HLH-2004方案联合支持治疗1或2周后，所有患者均获得临床缓解，HPS的实验室指标得到改善。4例患者及时给予SMILE联合化疗，其中2例达到完全缓解（CR）并长期生存，1例达到部分缓解（PR），停药后复发死亡，1例死于淋巴瘤进展。另外2例患者未及时接受化疗，HPS迅速复发，因淋巴瘤进展，均死于严重肝功能不全和凝血功能障碍。
NK/T-LAHPS是一种预后不良、通常在疾病晚期或终末期发生的致命性疾病。基于HLH-2004的方案联合综合治疗有望用于NK/T-LAHPS患者，可能延缓疾病进展并为原发性疾病的治疗提供机会。一旦HPS的实验室指标改善，及时用SMILE联合化疗治疗淋巴瘤很重要，这对改善预后具有重要意义。
