儿童EB病毒阳性T/NK细胞淋巴组织增殖性疾病21例临床病理特点及预后分析

Clinicopathological and Prognostic Analysis of 21 Children with Epstein-Barr Virus Positive T and NK-Cell Lymphoproliferative Disease

摘要: 目的：分析儿童EB病毒阳性T/NK细胞淋巴组织增殖性疾病临床病理特征及预后。方法：回顾性分析了21例儿童EB病毒阳性T/NK细胞淋巴组织增殖性疾病的临床病理资料，采用Kaplan-Meier法分析预后影响因素。结果：21例儿童EBV-T/NK-LPDs中男孩12例，女孩9例，发病年龄2~14岁(中位年龄8岁)。CAEBV 9例，HV-LPD 8例，CSEBV + TCL 4例，发病年龄分别为7~14岁(中位年龄10岁)，2~12岁(中位年龄6岁)、6~12岁(中位年龄8.5岁)。临床主要表现为发热(17/21)、肝脏肿大(15/21)、脾脏肿大(14/21)、淋巴结肿大(11/21)和皮疹(10/21)，伴全血细胞减少(10/21)、肝功能异常(9/21)、凝血功能障碍(7/21)、HLH (7/21)及肾功能异常(3/21)。21例患儿全血EBV-DNA拷贝数明显升高，超过104 copies/ml。组织病理特点为EB病毒感染的淋巴细胞增生，细胞形态多样。免疫组化：CD3、TIA-1阳性，部分合并CD56阳性。EBER原位杂交阳性。Ki-67增殖指数10%~90%。2例CAEBV、2例CSEBV + TCL及1例HV-LPD患儿检测到TCRγ基因克隆性重排。治疗策略包括抗病毒、糖皮质激素、联合化疗和HLH方案，1例患儿接受造血干细胞移植。随访20例患儿，随访时间0.3~59个月，死亡16例，存活4例。单因素分析结果：血小板减少(P = 0.013)、LDH升高(P = 0.003)、胆红素升高(P = 0)、肾功能异常(P = 0.02)、凝血功能障碍(P = 0)、合并HLH (P = 0)是预后不良的影响因素。结论：儿童EBV-T/NK-LPDs临床罕见，侵袭性强，接受抗病毒、糖皮质激素或按HLH方案治疗，病死率仍高。血小板减少、LDH升高、胆红素升高、肾功能异常、凝血功能障碍、合并HLH与不良预后相关。

Abstract: Objective: To analyze the clinicopathological features and prognosis factors of Epstein-Barr virus positive T and NK-cell lymphoproliferative diseases of children. Methods: The clinicopathological data of 21 children with Epstein-Barr virus positive T and NK-cell lymphoproliferative diseases were retrospectively analyzed according to clinicopathological subtypes. Kaplan-Meier method was used to analyze the prognostic factors. Results: Among the 21 patients with this disease, 12 were males and 9 were females. And the age of onset ranged from 2 to 14 years (median onset age, 8 years), 9 of CAEBV, 8 of HV-LPD, and 4 of CSEBV + TCL. The onset ages were 7~14 years (median on-set age, 10 years), 2~12 years (median onset age, 6 years) and 6~12 years (median onset age, 8.5 years) separately. The main manifestations included fever (17/21), hepatomegaly (15/21), sple-nomegaly (14/21), lymphadenopathy (11/21) and rash (10/21). Laboratory examination showed pancytopenia (10/21), abnormal liver function (9/21), coagulation dysfunction (7/21), HLH (7/21) and abnormal kidney function (3/21). EBV genome lode in the peripheral blood of 21 patients was more than 104 copies/ml. Histopathology is characterized by EBV positive lymphocytes prolifera-tion with diverse morphology. The immunophenotype showed positive for CD3 and TIA-1(+), and partial positive for CD56. EBER-ISH positive cells were seen in all cases. The Ki-67 index was range from 10 % to 90 %. Clonal TCR-γ gene rearrangement was detected in 2 of CAEBV, 2 of CSEBV + TCL, and 1 of HV-LPD. The treatment strategies included antiviral, glucocorticoid, combined chemother-apy and HLH treatment regimen. One child received hematopoietic stem cell transplantation. 20 children were followed up with a follow-up time from 0.3 to 59 months, 16 children died, 4 children survived. Univariate analysis showed that thrombocytopenia (P = 0.013), elevated LDH (P = 0.003), elevated bilirubin (P = 0), renal dysfunction (P = 0.02), coagulation dysfunction (P = 0), and the presence of HLH (P = 0) were associated with poor prognosis. Conclusion: EBV-T/NK-LPDs of chil-dren is rare and aggressive. The outcome of antiviral therapy, glucocorticoid therapy alone or HLH treatment regimens, is unsatisfactory. Thrombocytopenia, elevated LDH, elevated bilirubin, ab-normal renal function, coagulation dysfunction and HLH are associated with poor prognosis.