初诊伴自身免疫性溶血性贫血的侵袭性非霍奇金淋巴瘤特征分析

Characteristic analysis of aggressive non-Hodgkin's lymphoma complicated by autoimmune hemolytic anemia

目的:探讨首发伴自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)的侵袭性非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)的临床及实验室特征。方法:收集2013年9月至2016年7月苏州大学附属第二医院收治的6例首发伴AIHA的侵袭性NHL患者的临床资料,分析患者的发病情况、疾病进展、治疗及预后相关因素。结果:2013年9月至2016年7月苏州大学附属第二医院收治初发侵袭性NHL 155例,起病伴AIHA为6例(3.9%),其中男性3例,女性3例;中位年龄67(62~74)岁。首发症状包括:全身多发淋巴结肿大5例、发热3例、多发骨破坏并骨痛1例,均表现血红蛋白进行性下降。6例患者病理类型分别为:弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)3例,其中1例Bcl-2(+)Bcl-6(+)c-myc(+)三表达,1例CD5阳性;1例外周T细胞淋巴瘤-非特指型(peripheral T-cell lymphoma-not otherwise specified,PTCL-NOS);2例血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T-cell lymphoma,AITCL)。色素原位杂交(chromogenic in situ hybridization,CISH)法检测石蜡组织EB病毒基因(Epstein-Barr virus-m RNA,EBV-m RNA)(EBER)的表达:所检测5例均阳性。6例ECOG评分3~4分,Ann-Arbor分期均为Ⅲ~Ⅳ期,IPI评分4~5分,均为高危组。淋巴瘤病理确诊时中位血红蛋白56(34~79)g/L、中位网织红细胞比例6.7(0.2~21.0)%;6例患者Coombs试验均阳性:6例抗C3阳性(1:64~1:2 048)、4例抗Ig G阳性(±~1:16);检测3例血浆EBV-DNA拷贝数均增高。6例患者中:1例AITCL确诊后放弃治疗;其余5例应用CHOP样方案±利妥昔单抗联合化疗2~8个疗程(4例化疗间歇期加强的松治疗),其中2例DLBCL持续完全缓解(complete response,CR),总生存时间(overall survival,OS)分别为20、14个月,另1例DLBCL及1例PTCL-NOS经2个疗程化疗后骨髓抑制期继发严重肺部感染、心功能衰竭死亡,OS分别为1.5、2个月,1例AITCL化疗4个疗程后疾病快速进展死亡,OS为4.5个月。结论:侵袭性NHL首发伴AIHA多见于老年患者,EBV感染率高,溶血进展快、程度严重,化疗耐受性差,总体预后差,早期死亡率高。早期诊断及有效化疗可能改善预后。

Objective： To explore the clinical characteristics and laboratory data of aggressive non-Hodgkin＇s lymphoma（NHL） complicated by autoimmune hemolytic anemia（AIHA）. Methods： Data of six patients with aggressive NHL complicated by AIHA treated at the Second Affiliated Hospital of Suzhou University between September 2013 and July 2016 were reviewed retrospectively. The onset symptoms, disease progression, therapy, and prognostic factors were analyzed. Results： From September 2013 to July 2016, 155 patients with aggressive NHL were treated in our hospital. Six of them were complicated by AIHA（3.9%）, with three males and three females, aged from 62 to 74. The median age was 67 years. The first clinical symptoms included the following： five presented with lymphadenectasis, three had fever, and one presented with multiple bone destruction and bone pain, all complicated by progressive hemoglobin decrease. Histological examination of the six patients revealed three cases with diffuse large B-cell lymphoma（DLBCL）, including one case with positive Bcl-2, Bcl-6, and C-myc, and one case with positive CD5; one case was peripheral T-cell lymphoma-not otherwise specified（PTCL-NOS）; and two cases with angioimmunoblastic T-cell lymphoma（AITCL）. Epstein-Barr virus（EBV）-m RNA（EBER）was detected by chromogenic in situ hybridization（CISH）. Up to 100%（5/5） cases were EBER-positive. Eastern Cooperative Oncology Group scores of the six patients were three to four. All six cases were in the Ann-Arbor stagesⅢ-Ⅳ and International Prognostic Index score 4-5. All cases belonged to the high risk group. At the time when lymphoma was confirmed by pathology, the median level of hemoglobin was 56（34-79） g/L. The median ratio of reticulocytes was 6.7（0.2-21.0）%. The positive rate of Coombs test was 100%. All cases showed autoantibodies against C3（1 ： 64-1 ： 2 048）. Four cases showed antoantibodies against G antigen（±~1 ： 16）. The plasma concentration of EBV DNA of three patients was detected and all increased. Except that 1 case gave up treatment, five patients received the chemotherapy with CHOP or R-CHOP. Four patients received prednisone between chemotherapy intermittent period. Two cases showed sustained complete response（CR）. The overall survival（OS） was 20 and 14 months. Another patient with DLBCL and one patient with PTCL-NOS died from secondary severe pulmonary infection and heart failure during the myelosuppression. The OS times were 1.5 and 2 months, respectively. One patient with AITCL died in the disease progression after four cycles of chemotherapy. The OS was 4.5 months. Conclusion： Aggressive NHL complicated by AIHA is common in older patients with poor prognosis. The incidence rate of EBV infection was high, and hemolysis is rapid and serious. The patients＇ tolerance to chemotherapy was poor. Early diagnosis and effective chemotherapy may improve patients＇ prognosis.