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Haematologica. 2019 Dec 26. pii: haematol.2019.229252. doi: 10.3324/haematol.2019.229252. [Epub ahead of print]

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

Author information

1
Dpt of Hematology, Medical Oncology, and Pneumology, University Medical Center, Mainz, Germany.
2
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany.
3
Oncology, Hematology and Bone Marrow Transplantation Unit, Klinikum Nord, Nürnberg, Germany.
4
Department of Laboratory Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden.
5
First Department of Medicine, Center for Oncology and Hematology, Wilhelminenspital, Vienna, Austria.
6
Department of Hematology, University Hospital, Heinrich Heine University Düsseldorf, Germany.
7
Klinik f. Innere Medizin II, Abt. Haematol. und Internist. Onkologie, Univ.-Klinikum Jena, Germany.
8
Klinik f. Innere Medizin II, Abt. Haemmatol. und Internist. Onkologie, Univ.-Klinikum Jena, Germany.
9
Dpt of Hematology and Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim,Germany.
10
III. Medical Department, Hematology and Oncology, Klinikum rechts der Isar, TUM, Munich, Germany.
11
Innere Klinik, Tumorforschung, University Hospital Essen, Germany.
12
Dpt of Transplantation Surgery, University Medical Center of the JGU, Mainz, Germany.
13
Institute for Transfusion Medicine, University Hospital Essen, Germany.
14
Institute of Virology and Immunobiology, University Medical Center Würzburg, Germany.
15
Lophius Biosciences, Regensburg, Germany.
16
Institute of Clinical Microbiology and Hygiene, University Medical Center Regensburg, Germany.
17
Dpt of Internal Medicine III, Hematology and Oncology, University Medical Center Regensburg, Germany daniel.wolff@ukr.de.

Abstract

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.

KEYWORDS:

Cell-mediated immunity; Cytomegalovirus; Infectious Disorders; Lymphocytes; Stem Cell Transplantation

PMID:
31879324
DOI:
10.3324/haematol.2019.229252
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