[Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation]

Zhonghua Nei Ke Za Zhi. 2023 Jul 1;62(7):826-832. doi: 10.3760/cma.j.cn112138-20221204-00904.
[Article in Chinese]

Abstract

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

目的: 分析在单倍体造血干细胞移植后的患者中采用莱特莫韦初级预防巨细胞病毒(CMV)感染的有效性及安全性。 方法: 回顾性队列研究。选择2022年5月1日至8月31日于北京大学血液病研究所接受单倍体造血干细胞移植、使用莱特莫韦作为CMV初级预防并满足如下标准的患者:移植后30 d内开始应用莱特莫韦,并持续应用至移植后90 d以上(莱特莫韦组)。按1∶4比例选择同期接受单倍体造血干细胞移植但未应用莱特莫韦的患者作为对照组。主要观察指标包括移植后CMV感染及CMV病的发生率,以及莱特莫韦对于急性移植物抗宿主病(aGVHD)、非复发死亡率(NRM)及骨髓抑制的可能影响。分类变量采用χ2检验、连续变量采用Mann-Whitney U检验进行统计。采用Kaplan-Meier法分析CMV感染发生率。 结果: 莱特莫韦组共纳入符合条件患者17例。莱特莫韦组患者年龄显著高于对照组(中位年龄43岁比15岁,Z=-4.28,P<0.001),两组患者性别及疾病分布等差异均无统计学意义(均P>0.05)。莱特莫韦组供者CMV血清学阴性的比例显著高于对照组(8/17比0/68,χ2=35.32,P<0.001)。莱特莫韦组17例患者中3例发生CMV再激活,发生率显著低于对照组(3/17比40/68,χ2=9.23,P=0.002),无CMV病发生。莱特莫韦对血小板植活时间(P=0.105)、aGVHD(P=0.348)及100天NRM(P=0.474)均无显著影响。 结论: 初步临床数据提示莱特莫韦可能有效降低单倍体造血干细胞移植后CMV感染的发生率,同时未增加aGVHD、NRM及骨髓抑制的发生风险。该结论仍需未来进行前瞻性随机对照研究以进一步验证。.

Publication types

  • English Abstract

MeSH terms

  • Antiviral Agents / therapeutic use
  • Cohort Studies
  • Cytomegalovirus
  • Cytomegalovirus Infections* / prevention & control
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Prospective Studies
  • Recurrence
  • Retrospective Studies

Substances

  • letermovir
  • Antiviral Agents