Greatly reduced risk of EBV reactivation in rituximab-experienced recipients of alemtuzumab-conditioned allogeneic HSCT.
Greatly reduced risk of EBV reactivation in rituximab-experienced recipients of alemtuzumab-conditioned allogeneic HSCT.
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DOI：
10.1038/bmt.2016.19
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发表时间：
2016-06
影响因子：
4.8
通讯作者：
Chaganti S
中科院分区：
文献类型：
--
作者：
Burns DM;Rana S;Martin E;Nagra S;Ward J;Osman H;Bell AI;Moss P;Russell NH;Craddock CF;Fox CP;Chaganti S
EBV相关性移植后淋巴增生性疾病(PTLD)仍然是异基因造血干细胞移植(allo-HSCT)的重要并发症。我们回顾分析了186名成人患者在单个中心接受连续的allo-HSCT后Alemtuzumab T细胞耗尽后EBV再激活的发生率和危险因素。1年内EBV再激活的累积发生率为48%(可信区间为41-55%)，高水平EBV再激活的发生率为18%(可信区间为13-24%)；8名患者同时诊断为PTLD。在高水平再激活的患者中，31/38(82%)在首次EBV qPCR阳性后仅2周内发生了这种情况。在单变量分析中，年龄50岁的⩾与EB病毒再激活的风险显著增加(危险比(HR)1.54，可信区间1.02-2.31；P=0.039)。此外，非霍奇金淋巴瘤的诊断与再激活风险的显著降低相关(HR0.10，CI0.03-0.33；P=0.0001)，这一点在多因素检验中得到证实。重要的是，在allo-HSCT前6个月内接受利妥昔单抗治疗也是缺乏EB病毒再激活的高度预测因素(HR0.18，CI0.07-0.48；P=0.001)，尽管与非霍奇金淋巴瘤有明显的混淆。我们的数据强调了与alemtuzumab相关的PTLD的风险。此外，我们报告了临床上重要的观察结果，即在移植围手术期使用利妥昔单抗可能为PTLD提供有效的预防措施。
EBV-associated post-transplant lymphoproliferative disease (PTLD) remains an important complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). We retrospectively analysed the incidence and risk factors for EBV reactivation in 186 adult patients undergoing consecutive allo-HSCT with alemtuzumab T-cell depletion at a single centre. The cumulative incidence of EBV reactivation was 48% (confidence interval (CI) 41–55%) by 1 year, with an incidence of high-level EBV reactivation of 18% (CI 13–24%); 8 patients were concurrently diagnosed with PTLD. Amongst patients with high-level reactivation 31/38 (82%) developed this within only 2 weeks of first EBV qPCR positivity. In univariate analysis age⩾50 years was associated with significantly increased risk of EBV reactivation (hazard ratio (HR) 1.54, CI 1.02–2.31; P=0.039). Furthermore, a diagnosis of non-Hodgkin lymphoma (NHL) was associated with greatly reduced risk of reactivation (HR 0.10, CI 0.03–0.33; P=0.0001) and this was confirmed in multivariate testing. Importantly, rituximab therapy within 6 months prior to allo-HSCT was also highly predictive for lack of EBV reactivation (HR 0.18, CI 0.07–0.48; P=0.001) although confounding with NHL was apparent. Our data emphasise the risk of PTLD associated with alemtuzumab. Furthermore, we report the clinically important observation that rituximab, administered in the peri-transplant period, may provide effective prophylaxis for PTLD.