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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

  • Martin Schmidt-HieberEmail author
  • Gloria Tridello
  • Per Ljungman
  • Malgorzata Mikulska
  • Nina Knelange
  • Didier Blaise
  • Gerard Socié
  • Liisa Volin
  • Nicole Blijlevens
  • Nathalie Fegueux
  • Ibrahim Yakoub-Agha
  • Edouard Forcade
  • Johan Maertens
  • Patrice Chevallier
  • Jakob Passweg
  • Jan Cornelissen
  • Nigel Russell
  • Charles Craddock
  • Jean Henri Bourhis
  • Tony Marchand
  • Péter Reményi
  • Jean Yves Cahn
  • Mauricette Michallet
  • Silvia Montoto
  • Nicolaus Kröger
  • Bertram Glaß
  • Jan Styczynski
Original Article

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.

Keywords

Allogeneic hematopoietic stem cell transplantation Chronic hematological malignancies Cytomegalovirus Serostatus Survival 

Notes

Authorship

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.

Compliance with ethical standards

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.

Ethical approval

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.

Informed consent

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

Supplementary material

277_2019_3669_MOESM1_ESM.docx (45 kb)
ESM 1 (DOCX 44.8kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Martin Schmidt-Hieber
    • 1
    Email author
  • Gloria Tridello
    • 2
  • Per Ljungman
    • 3
  • Malgorzata Mikulska
    • 4
  • Nina Knelange
    • 5
  • Didier Blaise
    • 6
  • Gerard Socié
    • 7
  • Liisa Volin
    • 8
  • Nicole Blijlevens
    • 9
  • Nathalie Fegueux
    • 10
  • Ibrahim Yakoub-Agha
    • 11
  • Edouard Forcade
    • 12
  • Johan Maertens
    • 13
  • Patrice Chevallier
    • 14
  • Jakob Passweg
    • 15
  • Jan Cornelissen
    • 16
  • Nigel Russell
    • 17
  • Charles Craddock
    • 18
  • Jean Henri Bourhis
    • 19
  • Tony Marchand
    • 20
  • Péter Reményi
    • 21
  • Jean Yves Cahn
    • 22
  • Mauricette Michallet
    • 23
  • Silvia Montoto
    • 24
  • Nicolaus Kröger
    • 25
  • Bertram Glaß
    • 26
  • Jan Styczynski
    • 27
  1. 1.Clinic for Hematology and OncologyCarl-Thiem-KlinikumCottbusGermany
  2. 2.Policlinico G.B. RossiVeronaItaly
  3. 3.Karolinska University HospitalStockholmSweden
  4. 4.DISSAL, Division of Infectious DiseasesUniversity of Genova and IRCCS Ospedale Policlinico San MartinoGenoaItaly
  5. 5.EBMT Data OfficeLeidenNetherlands
  6. 6.Institute Paoli CalmettesMarseilleFrance
  7. 7.Hopital St. LouisParisFrance
  8. 8.HUCH Comprehensive Cancer CenterHelsinkiFinland
  9. 9.Nijmegen Medical CentreRadboud UniversityNijmegenNetherlands
  10. 10.CHU LapeyronieMontpellierFrance
  11. 11.CHU de Lille, LIRIC, INSERM U995Université de LilleLilleFrance
  12. 12.CHU BordeauxService d’Hematologie et Therapie CellulaireBordeauxFrance
  13. 13.University Hospital GasthuisbergLeuvenBelgium
  14. 14.CHU NantesNantesFrance
  15. 15.University HospitalBaselSwitzerland
  16. 16.Erasmus MC Cancer InstituteRotterdamNetherlands
  17. 17.Nottingham UniversityNottinghamUK
  18. 18.Queen Elizabeth HospitalBirminghamUK
  19. 19.Gustave Roussy Institute de CancérologieVillejuifFrance
  20. 20.Centre Hospitalier Universitaire de RennesRennesFrance
  21. 21.St. Istvan & St. Laszlo HospitalBudapestHungary
  22. 22.CHU Grenoble Alpes GrenobleGrenobleFrance
  23. 23.Centre Hospitalier Lyon SudLyonFrance
  24. 24.Barts Health NHS Trust LondonSt Bartholomew’s HospitalLondonUK
  25. 25.University Hospital EppendorfHamburgGermany
  26. 26.Clinic for Hematology and Stem Cell TransplantationHELIOS Clinic Berlin-BuchBerlinGermany
  27. 27.Collegium Medicum UMKUniversity HospitalBydgoszczPoland

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