Haematologica (Dec 2019)

Standardized monitoring of cytomegalovirus-specific immunity can improve risk stratification of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation

  • Eva Wagner-Drouet,
  • Daniel Teschner,
  • Christine Wolschke,
  • Dietlinde Janson,
  • Kerstin Schäfer-Eckart,
  • Johannes Gärtner,
  • Stephan Mielke,
  • Martin Schreder,
  • Guido Kobbe,
  • Mustafa Kondakci,
  • Inken Hilgendorf,
  • Marie von Lilienfeld-Toal,
  • Stefan Klein,
  • Daniela Heidenreich,
  • Sebastian Kreil,
  • Mareike Verbeek,
  • Sandra Grass,
  • Markus Ditschkowski,
  • Tanja Gromke,
  • Martina Koch,
  • Monika Lindemann,
  • Thomas Hünig,
  • Traudel Schmidt,
  • Anne Rascle,
  • Harald Guldan,
  • Sascha Barabas,
  • Ludwig Deml,
  • Ralf Wagner,
  • Daniel Wolff

DOI
https://doi.org/10.3324/haematol.2019.229252
Journal volume & issue
Vol. 106, no. 2

Abstract

Read online

Recurrence of cytomegalovirus reactivation remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Monitoring cytomegalovirus-specific cellular immunity using a standardized assay might improve the risk stratification of patients. A prospective multicenter study was conducted in 175 intermediate- and high-risk allogeneic hematopoietic stem cell transplant recipients under preemptive antiviral therapy. Cytomegalovirus-specific cellular immunity was measured using a standardized IFN-γ ELISpot assay (T-Track® CMV). Primary aim was to evaluate the suitability of measuring cytomegalovirus-specific immunity after end of treatment for a first cytomegalovirus reactivation to predict recurrent reactivation. 40/101 (39.6%) patients with a first cytomegalovirus reactivation experienced recurrent reactivations, mainly in the high-risk group (cytomegalovirus-seronegative donor/cytomegalovirus-seropositive recipient). The positive predictive value of T-Track® CMV (patients with a negative test after the first reactivation experienced at least one recurrent reactivation) was 84.2% in high-risk patients. Kaplan-Meier analysis revealed a higher probability of recurrent cytomegalovirus reactivation in high-risk patients with a negative test after the first reactivation (hazard ratio 2.73; p=0.007). Interestingly, a post-hoc analysis considering T-Track® CMV measurements at day 100 post-transplantation, a time point highly relevant for outpatient care, showed a positive predictive value of 90.0% in high-risk patients. Our results indicate that standardized cytomegalovirus-specific cellular immunity monitoring may allow improved risk stratification and management of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. This study was registered at www.clinicaltrials.gov as #NCT02156479.