儿童NK/T细胞淋巴瘤相关噬血细胞综合征6例临床分析

Children's NK/T Cell Lymphoma-Associated Hemophagocytic Syndrome:Clinical Analysis of 6 Cases

目的：探讨儿童NK/T细胞淋巴瘤相关噬血细胞综合征（NK/T-LAHPS）的临床特征、治疗方法及预后。方法：对6例NK/T-LAHS患儿的临床资料进行回顾性分析。6例NK/T-LAHS患者中,男4例,女2例,中位年龄5（1.75-11）岁,4例以噬血细胞综合征（HPS）为首发表现,2例在疾病进展中发生HPS,临床上以持续高热（6/6）、肝肿大（6/6）、脾肿大（6/6）、血象指标进行性下降（6/6）为突出表现,铁蛋白（2179-15000 ng/ml）、乳酸脱氢酶（608-3899 IU/L）升高明显,EBV-DNA载量较高（均大于10-5 copies/ml）;另外,低蛋白血症（6/6）、肝功能异常（5/6）、低纤维蛋白原血症（5/6）、高甘油三酯血症（3/6）、骨髓中噬血现象（5/6）常见。结果：给予HLH-2004方案为基础的综合治疗1-2周,HPS病情有不同程度改善。4例及时接受改良的SMILE方案化疗后,其中2例获完全缓解并长期存活;1例获部分缓解,但停药后原发病复发死亡;1例化疗无效,病情进展而死亡。另外2例未能及时给予改良SMILE方案化疗,HPS很快复发,患者并发严重肝功能损害、凝血功能异常,最终死亡。结论：NK/T细胞淋巴瘤合并HPS时,多为淋巴瘤的进展期或终末阶段,预后差,以HLH-2004方案为基础的综合治疗可以延缓疾病进展,为原发病治疗创造机会,之后及时应用SMILE化疗方案进行原发病治疗,可以改善患者预后。

Objective：To study the clinical features,treatment and prognosis of patients with NK/T cell lymphomaassociated hemophagocytic syndrome（NK/T-LAHPS）.Methods：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 of4 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（ 〉10^5 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）.Results：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.Conclusion：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/TLAHPS,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.