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The prognostic impact of the cytomegalovirus serostatus in patients with chronic hematological malignancies after allogeneic hematopoietic stem cell transplantation: a report from the Infectious Diseases Working Party of EBMT

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Abstract

It has been shown recently that donor and/or recipient cytomegalovirus (CMV) seropositivity is associated with a significant overall survival (OS) decline in acute leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We now analyzed the prognostic impact of the donor/recipient CMV serostatus in 6968 patients with chronic hematological malignancies who underwent allo-HSCT. Donor and/or recipient CMV seropositivity was associated with a significantly reduced 2-year progression-free survival (PFS, 50% vs. 52%, p = 0.03) and OS (62% vs. 65%, p = 0.01). Multivariate Cox regression analyses showed an independent negative prognostic impact of donor and/or recipient CMV seropositivity on PFS (HR, 1.1; 95% CI, 1.0–1.2; p = 0.03), OS (HR, 1.1; 95% CI, 1.0–1.2; p = 0.003), and non-relapse mortality (HR, 1.2; 95% CI, 1.0–1.3; p = 0.02). OS decline was strongest for CMV-seropositive recipients with a CMV-seronegative donor (HR, 1.2; 95% CI, 1.1–1.3), followed by CMV-seropositive patients with a CMV-seropositive donor (HR, 1.1; 95% CI, 1.0–1.2). Conversely, OS did not differ significantly between CMV-seronegative recipients allografted from a CMV-seropositive donor (HR, 1.0; 95% CI, 0.9–1.2) and patients with donor/recipient CMV seronegativity (p = 0.001 for the four groups together). Non-relapse mortality was also significantly (p = 0.01) higher for CMV-seropositive patients with a CMV-seronegative graft (HR, 1.2; 95% CI, 1.1–1.4) than for CMV-seropositive patients with a CMV-seropositive graft (HR, 1.1; 95% CI, 0.9–1.2) or CMV-seronegative recipients with a CMV-seropositive graft (HR, 1.0; 95% CI, 0.8–1.2). Donor and/or recipient CMV seropositivity still results in an OS decline in patients with chronic hematological malignancies who have undergone allo-HSCT. However, this OS decline seems to be lower than that described for acute leukemia patients previously.

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Authors and Affiliations

  1. Clinic for Hematology and Oncology, Carl-Thiem-Klinikum, Cottbus, Germany

    Martin Schmidt-Hieber

  2. Policlinico G.B. Rossi, Verona, Italy

    Gloria Tridello

  3. Karolinska University Hospital, Stockholm, Sweden

    Per Ljungman

  4. DISSAL, Division of Infectious Diseases, University of Genova and IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Malgorzata Mikulska

  5. EBMT Data Office, Leiden, Netherlands

    Nina Knelange

  6. Institute Paoli Calmettes, Marseille, France

    Didier Blaise

  7. Hopital St. Louis, Paris, France

    Gerard Socié

  8. HUCH Comprehensive Cancer Center, Helsinki, Finland

    Liisa Volin

  9. Nijmegen Medical Centre, Radboud University, Nijmegen, Netherlands

    Nicole Blijlevens

  10. CHU Lapeyronie, Montpellier, France

    Nathalie Fegueux

  11. CHU de Lille, LIRIC, INSERM U995, Université de Lille, Lille, France

    Ibrahim Yakoub-Agha

  12. CHU Bordeaux, Service d’Hematologie et Therapie Cellulaire, Bordeaux, France

    Edouard Forcade

  13. University Hospital Gasthuisberg, Leuven, Belgium

    Johan Maertens

  14. CHU Nantes, Nantes, France

    Patrice Chevallier

  15. University Hospital, Basel, Switzerland

    Jakob Passweg

  16. Erasmus MC Cancer Institute, Rotterdam, Netherlands

    Jan Cornelissen

  17. Nottingham University, Nottingham, UK

    Nigel Russell

  18. Queen Elizabeth Hospital, Birmingham, UK

    Charles Craddock

  19. Gustave Roussy Institute de Cancérologie, Villejuif, France

    Jean Henri Bourhis

  20. Centre Hospitalier Universitaire de Rennes, Rennes, France

    Tony Marchand

  21. St. Istvan & St. Laszlo Hospital, Budapest, Hungary

    Péter Reményi

  22. CHU Grenoble Alpes Grenoble, Grenoble, France

    Jean Yves Cahn

  23. Centre Hospitalier Lyon Sud, Lyon, France

    Mauricette Michallet

  24. Barts Health NHS Trust London, St Bartholomew’s Hospital, London, UK

    Silvia Montoto

  25. University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  26. Clinic for Hematology and Stem Cell Transplantation, HELIOS Clinic Berlin-Buch, Berlin, Germany

    Bertram Glaß

  27. Collegium Medicum UMK, University Hospital, Bydgoszcz, Poland

    Jan Styczynski

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  1. Martin Schmidt-Hieber
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Contributions

M.S.H., G.T., P.L., M.Mik., and J.S. designed the research. M.S.H., G.T., P.L., M.Mik., N.K., D.B., G.S., L.V., N.B., N.F., I.Y.A., E.F., J.M, P.C., J.P., J.C., N.R., C.C., J.H.B., T.M., P.R., J.Y.C., M.Mic., S.M., N.K., B.G., and J.S. provided important clinical data and/or performed statistical analyses. M.S.H. wrote the first draft of the manuscript. All authors approved the final version of the manuscript. A complete list of contributors appears in the online data supplement.

The authors thank all allogeneic transplantation centers of the European Bone Marrow Transplantation group for reporting the data to this registry.

Corresponding author

Correspondence to Martin Schmidt-Hieber.

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Conflict of interest

I.Y.A received honorarium from Biotest and MSD Sharp & Dohme GmbH that commercialize anti-CMV drugs. The other authors declare that they have no conflicts of interest.

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All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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According to EBMT policy, patients give informed consent for data reporting to the EBMT registry.

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Schmidt-Hieber, M., Tridello, G., Ljungman, P. et al. The prognostic impact of the cytomegalovirus serostatus in patients with chronic hematological malignancies after allogeneic hematopoietic stem cell transplantation: a report from the Infectious Diseases Working Party of EBMT. Ann Hematol 98, 1755–1763 (2019). https://doi.org/10.1007/s00277-019-03669-z

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