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

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

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

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.      «

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 immuni...     »