Microbiology and Virology Unit, IRCCS Policlinico San Matteo, Pavia, Italy.
Molecular Medicine Department, University of Pavia, Pavia, Italy.
Transplant Cell Ther. 2022 Apr;28(4):211.e1-211.e9. doi: 10.1016/j.jtct.2022.01.008. Epub 2022 Jan 15.
Letermovir (LTV), recently approved for the prophylaxis of human cytomegalovirus (HCMV) reactivation after hematopoietic stem cell transplantation (HSCT), has been shown to decrease the rate of infection in the first months post-transplantation. The aim of this study was to evaluate the impact of LTV prophylaxis on immune reconstitution and late-onset infection. We studied HCMV infection and HCMV-specific T cell reconstitution in 2 matched groups of HSCT recipients, those treated with LTV prophylaxis (n = 30; LTV group) and those receiving preemptive therapy (n = 31; PET group). We analyzed the rates of graft-versus-host disease (GVHD), neutropenia, baseline disease recurrence, and overall survival in the 2 groups. Clinically significant infections necessitating preemptive therapy showed a similar rate in the 2 groups (PET: 21 of 31 [68%]; LTV: 17 of 30 [57%]; P = .434) but occurred significantly later (after prophylaxis discontinuation) in the LTV group. There was no between-group difference in peak HCMV DNAemia level (P = .232). HCMV-specific T cell recovery was delayed by approximately 100 days in the LTV group. HCMV-specific CD4 and CD8 T cell counts were significantly lower in the LTV group at days 120 to 360 and days 90 to 120, respectively. A lower rate of chronic GVHD (P = .024) was seen in the LTV group. Time to engraftment, rate of disease relapse, and 1-year survival were not different between the 2 groups, whereas trends toward a lower rate of neutropenia (P = .124) and a higher rate of acute GVHD grade III-IV (P = .103) were observed in the LTV group. Because LTV prophylaxis delays HCMV infection and HCMV-specific immune reconstitution, immunologic and virologic monitoring should be implemented after discontinuation of prophylaxis. The potential effect of LTV prophylaxis in reducing chronic GVHD should be evaluated in prospective studies.
替诺福韦酯（LTV）最近被批准用于预防造血干细胞移植（HSCT）后人类巨细胞病毒（HCMV）的再激活，已被证明可降低移植后第一个月的感染率。本研究旨在评估 LTV 预防对免疫重建和迟发性感染的影响。我们研究了接受 LTV 预防治疗（n=30；LTV 组）和接受抢先治疗（n=31；PET 组）的 HSCT 受者的 HCMV 感染和 HCMV 特异性 T 细胞重建情况。我们分析了两组患者移植物抗宿主病（GVHD）、中性粒细胞减少症、基线疾病复发和总生存率的发生率。两组患者需要抢先治疗的临床显著感染率相似（PET：31 例中的 21 例[68%]；LTV：30 例中的 17 例[57%]；P=0.434），但在 LTV 组中发生时间明显延迟（在预防治疗停药后）。两组间峰值 HCMV DNAemia 水平无差异（P=0.232）。LTV 组 HCMV 特异性 T 细胞恢复延迟约 100 天。LTV 组在第 120 至 360 天和第 90 至 120 天时，HCMV 特异性 CD4 和 CD8 T 细胞计数明显较低。LTV 组慢性 GVHD 发生率较低（P=0.024）。两组间植入时间、疾病复发率和 1 年生存率无差异，而 LTV 组中性粒细胞减少症发生率较低（P=0.124）和急性 GVHD Ⅲ-Ⅳ级发生率较高（P=0.103）的趋势。由于 LTV 预防可延迟 HCMV 感染和 HCMV 特异性免疫重建，因此在预防治疗停药后应进行免疫和病毒学监测。应在前瞻性研究中评估 LTV 预防在降低慢性 GVHD 中的潜在作用。
