摘要
目的 观察再生障碍性贫血(AA)患者行异基因造血干细胞移植(allo-HSCT)后应用小剂量利妥昔单抗预防EB病毒(EBV)感染的效果,探讨其安全性.方法 回顾性分析2017年3月-2020年8月河南省肿瘤医院行allo-HSCT的91例AA患者的临床资料.53例移植第5天给予单次小剂量利妥昔单抗预防EBV感染者为利妥昔单抗组;38例移植前1 d起口服阿昔洛韦(400 mg/次,2次/d)至免疫抑制剂停用预防EBV感染者为对照组;2组移植前常规预防巨细胞病毒感染、移植物抗宿主病.记录2组移植后30、60、90 d血常规、免疫球蛋白水平及CD3+、CD20+淋巴细胞数量.随访3年,记录2组移植后EBV感染、巨细胞病毒感染、其他感染、淋巴细胞增殖性疾病、移植物抗宿主病发生情况及生存情况.结果 (1)2组回输单个核细胞数量、CD34+细胞数量、粒细胞植入时间、血小板植入时间、造血重建率、Ⅱ～Ⅳ级急性移植物抗宿主病及慢性移植物抗宿主病发生率比较差异均无统计学意义(P＞0.05).(2)利妥昔单抗组移植后30、60、90 d 淋巴细胞计数[0.2(0.1,0.4)× 109/L、0.2(0.1,0.3)× 109/L、0.3(0.1,1.5)× 109/L]均低于对照组[0.5(0,4.1)×109/L、0.6(0.1,2.5)× 109/L、1.3(0.3,2.9)× 109/L](P＜0.05),移植后 30 d IgA 水平[0.95(0.18,2.29)g/L]低于对照组[1.59(0.77,2.68)g/L](P＜0.05).(3)随访至 2023年12月31日,利妥昔单抗组EBV 感染率(20.75％)、EBV 感染后 EBV-DNA 最高载量[9.60(2.20,51.30)× 103 拷贝/mL]、EBV 感染后 EBV-DNA载量＞1× 104拷贝/mL 比率(9.43％)均低于对照组[65.79％、36.40(6.60,154.00)× 103 拷贝/mL、26.32％](P＜0.05),移植后EBV初次感染时间[77(36,420)d]晚于对照组[33(23,53)d](P＜0.05),初次EBV感染时EBV-DNA载量及淋巴细胞增殖性疾病发生率与对照组比较差异均无统计学意义(P＞0.05).利妥昔单抗组重度感染、巨细胞病毒感染发生率与对照组比较差异均无统计学意义(P＞0.05).利妥昔单抗组死亡9例,对照组死亡11例,利妥昔单抗组3年总生存率(82.30％)与对照组(70.00％)比较差异无统计学意义(P＞0.05).结论 AA患者allo-HSCT后第5天应用小剂量利妥昔单抗可有效预防移植后EBV感染,低丙种球蛋白血症程度较轻,不影响造血重建,不增加其他感染,较安全.
Abstract
Objective To explore the efficacy of low-dose rituximab(RTX)on preventing Epstein-Barr virus(EBV)infection in aplastic anemia(AA)patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT),and to explore its safety.Methods Ninety-one AA patients underwent allo-HSCT in Henan Cancer Hospital from March,2017 to August,2020,and their clinical data were retrospectively analyzed.Among these 91 patients,53 patients received low-dose RTX once on the 5th day after allo-HSCT(RTX group),and the other 38 patients received oral acyclovir(400 mg once,twice a day)from the day before allo-HSCT to the time for termination of immunosuppressant to prevent EBV infection(control group).All patients in two groups received routine treatment to prevent cytomegalovirus infection and graft-versus-host disease(GVHD).The blood routine results,serum immunoglobulin levels,and counts of CD3+and CD20+lymphocytes were recorded on the 30th,60th and 90th days after allo-HSCT.The 3-year follow-up was done to record the occurrences of EBV infection,cytomegalovirus infection,other infections,post-transplant lymphoproliferative disorder,GVHD and survival in two groups.Results(1)There were no significant differences in the count of mononuclears cells reinfused,count of CD34+cells,granulocyte and platelet implantation time,rate of blood reconstruction,and post-transplant incidence of Ⅱ to Ⅳ acute and chronic GVHD between two groups(P＞0.05).(2)The counts of lymphocyte on the 30th,60th and 90th days after allo-HSCT were lower in RTX group[0.2(0.1,0.4)×109/L,0.2(0.1,0.3)×109/L,0.3(0.1,1.5)×109/L]than those in control group[0.5(0,4.1)×109/L,0.6(0.1,2.5)×109/L,1.3(0.3,2.9)×109/L](P＜0.05).The level of IgA on the 30th day after allo-HSCT was lower in RTX group[0.95(0.18,2.29)g/L]than that in control group[1.59(0.77,2.68)g/L](P＜0.05).(3)The follow-up was done till December 31,2023,which showed that the rate of EBV infection,maximum EBV-DNA load and rate of EBV-DNA load＞1 × 104 copy/mL were lower in RTX group[20.75％,9.60(2.20,51.30)× 103copy/mL,9.43％]than those in control group after allo-HSCT[65.79％,36.40(6.60,154.00)× 103 copy/mL,26.32％](P＜0.05).The first-time EBV infection developed later in RTX group[77(36,420)d]than that in control group[33(23,53)d](P＜0.05).There were no significant differences in the EBV-DNA load of the first-time EBV infection,the incidence of post-transplant lymphoproliferative disorder,and the rates of severe infection and cytomegalovirus infection after allo-HSCT between two groups(P＞0.05).There were 9 deaths in RTX group and 11 deaths in control group.The 3-year overall survival rate showed no significant difference between RTX group(82.30％)and control group(70.00％)(P＞0.05).Conclusion The use of low-dose RTX on the 5th day after allo-HSCT can significantly reduce the rate of EBV infection in AA patients,with the mild hypogammaglobulinemia,no influence on blood reconstruction and no increase of other infection rates,and it is safe.
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