Upper and/or Lower Respiratory Tract Infection Caused by Human Metapneumovirus After Allogeneic Hematopoietic Stem Cell Transplantation

Author:

Piñana Jose Luis12,Tridello Gloria3,Xhaard Aliénor4,Wendel Lotus5,Montoro Juan6,Vazquez Lourdes7,Heras Inmaculada8,Ljungman Per910,Mikulska Malgorzata1112,Salmenniemi Urpu13,Perez Ariadna12,Kröger Nicolaus14,Cornelissen Jan15,Sala Elisa16,Martino Rodrigo17,Geurten Claire1819,Byrne Jenny20,Maertens Johan21,Kerre Tessa22,Martin Murray23,Pascual Maria Jesús24,Yeshurun Moshe2526,Finke Jürgen27,Groll Andreas H28,Shaw Peter J29,Blijlevens Nicole30,Arcese William31,Ganser Arnold32,Suarez-Lledo Maria33,Alzahrani Mohsen34,Choi Goda35,Forcade Edouard36,Paviglianiti Annalisa37,Solano Carlos1238,Wachowiak Jacek39,Zuckerman Tsila40,Bader Peter41,Clausen Johannes42,Mayer Jiri43,Schroyens Wilfried44,Metafuni Elisabetta45,Knelange Nina5,Averbuch Dina46,de la Camara Rafael4748

Affiliation:

1. Hematology Department, Hospital Clinico Universitario de Valencia , Valencia , Spain

2. Fundación INCLIVA, Instituto de Investigación Sanitaria, Hospital Clínico, Universitario de Valencia , Valencia , Spain

3. Azienda Ospedaliera, Universitaria Integrata Verona , Verona , Italy

4. Service d’Hématologie-Greffe, Hôpital Saint-Louis, Université Paris-Diderot , Paris , France

5. Leiden Study Unit, EBMT , Leiden , The Netherlands

6. Hematology División, Hospital Universitario y Politécnico La Fe , Valencia , Spain

7. Hematology Department, Hospital Clinico Universitario de Salamanca , Salamanca , Spain

8. Hematology Department, Hospital Morales Meseguer , Murcia , Spain

9. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska Comprehensive Cancer Center, Karolinska University Hospital Huddinge , Stockholm , Sweden

10. Department of Medicine Huddinge, Karolinska Institutet , Stockholm , Sweden

11. Division of Infectious Diseases, Dipartimento di scienze della salute, University of Genoa , Genova , Italy

12. IRCCS Ospedale Policlinico San Martino , Genova , Italy

13. Hematology Department, Comprehensive Cancer Center, Helsinki University Central Hospital , Helsinki , Finland

14. Department for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf , Hamburg , Germany

15. Hematology Department, Erasmus Medical Center Cancer Institute , Rotterdam , The Netherlands

16. Department of Internal Medicine III, University Hospital of Ulm , Ulm , Germany

17. Hematology Department, Hospital de la Santa Creu I Sant Pau , Barcelona , Spain

18. Hematology Department, Birmingham Children's Hospital , Birmingham , United Kingdom

19. Centre Hospitalier Universitaire de Liege , Liege , Belgium

20. Hematology Department, Nottingham University , Nottingham , United Kingdom

21. Hematology Department, University Hospital Gasthuisberg , Leuven , Belgium

22. Hematology Department, Ghent University Hospital , Gent , Belgium

23. Hematology Department, Leicester Royal Infirmary , Leicester , United Kingdom

24. Hematology Department, Hospital Regional de Málaga , Malaga , Spain

25. Institution of Hematology, Rabin Medical Center , Petach-Tikva , Israel

26. Sackler School of Medicine, Tel-Aviv University , Tel-Aviv , Israel

27. Hematology Department, University of Freiburg , Freiburg , Germany

28. Infectious Disease Research Program, Department of Pediatric Hemtology and Oncology and Center for Bone Marrow Transplantation, University Children's Hospital , Muenster , Germany

29. The Children`s Hospital at Westmead , Sydney , Australia

30. Nijmegen Medical Centre , Nijmegen , The Netherlands

31. Hematology Department, Tor Vergata University of Rome , Rome , Italy

32. Hannover Medical School , Hannover , Germany

33. Hematology Department, Hospital Clinic , Barcelona , Spain

34. Department of Oncology, King Abdulaziz Medical City, Ministry of National Guard—Health Affairs , Riyadh , Saudi Arabia

35. University Medical Center Groningen, University of Groningen , Groningen , The Netherlands

36. Service d'Hématologie Clinique et Thérapie Cellulaire, Centre Hospitalier Universitaire Bordeaux , Bordeaux , France

37. Institut Català de Oncología—Hospital Duran i Reynals , Barcelona , Spain

38. Department of Medicine, University of Valencia , Valencia , Spain

39. Department of Pediatric Oncology, Hematology, and Hematopoietic Cell Transplantation, University of Medical Sciences , Poznan , Poland

40. Rambam Medical Center , Haifa , Israel

41. Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Department for Pediatrics and Adolescent Medicine, University Hospital, Goethe University , Frankfurt , Germany

42. Department of Internal Medicine I, Ordensklinikum Linz—Elisabethinen, Johannes Kepler University , Linz , Austria

43. Masaryk University Hospital Brno , Brno , Czech Republic

44. Antwerp University Hospital , Edegem , Belgium

45. Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica e EmatologiaGemelli Research Institute, Fondazione Policlinico Universitario Agostino Gemelli Research Institute, Roma , Italy

46. Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center , Jerusalem , Israel

47. Hematology Department, Hospital de la Princesa , Madrid , Spain

48. Hematology Department, Hospital Universitario Sanitas La Zarzuela , Madrid , Spain

Abstract

Abstract Background Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. Methods This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. Results We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. Conclusions These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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