Reactivation and dynamics of cytomegalovirus and Epstein-Barr virus after rabbit antithymocyte globulin and cyclosporine for aplastic anemia

Eur J Haematol. 2019 Oct;103(4):433-441. doi: 10.1111/ejh.13308. Epub 2019 Aug 21.

Abstract

Objectives: This study aimed to identify the natural course of cytomegalovirus (CMV)/Epstein-Barr virus (EBV) after rabbit antithymocyte globulin and cyclosporine (rATG-CsA) for aplastic anemia (AA).

Methods: In 113 prospectively observed AA patients treated with rATG-CsA, the CMV/EBV cohort was classified into two groups by baseline viremic status: no viremia (CMV-G1, n = 112; EBV-G1, n = 98) and the presence of viremia (CMV-G2, n = 1; EBV-G2, n = 13).

Results: In CMV-G1, the mean CMV load increased up to 3 months but was completely resolved from 6 months. The mean EBV load of EBV-G1 showed a peak at 1 month and then gradually decreased over time but remained detectable throughout the observation period. EBV-G2 showed fluctuating EBV dynamics. With reactivation rates of 38.4% in CMV-G1 and 62.2% in EBV-G1, a longer time to rATG-CsA from diagnosis and a lower absolute lymphocyte count at 1 month from rATG-CsA were significantly associated with CMV and EBV reactivation, respectively. The mean peak CMV and EBV loads of patients with CMV-related (3.5%) and EBV-related (0.9%) diseases were evidently higher than those of the remaining patients without CMV and EBV diseases in the respective cohort.

Conclusion: Considering frequent reactivation and distinct courses of CMV/EBV, virologic surveillance is recommended after rATG-CsA for AA.

Keywords: Epstein-Barr virus; aplastic anemia; cytomegalovirus; immunosuppressive therapy; thymoglobulin.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia, Aplastic / complications*
  • Anemia, Aplastic / drug therapy
  • Antilymphocyte Serum / adverse effects*
  • Antilymphocyte Serum / therapeutic use
  • Cyclosporine / adverse effects*
  • Cyclosporine / therapeutic use
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / etiology*
  • Cytomegalovirus Infections / virology*
  • Cytomegalovirus*
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / etiology*
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Herpesvirus 4, Human*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Treatment Outcome
  • Viral Load
  • Virus Activation*
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Cyclosporine
  • thymoglobulin