Association between CMV and Invasive Fungal Infections After Autologous Stem Cell Transplant in Lymphoproliferative Malignancies: Opportunistic Partnership or Cause-Effect Relationship?

International Journal of Molecular Sciences

Iole Cordone¹  Giulia Regazzo²  MariaGiulia Rizzo²  Maria Cantonetti³  William Arcese³  Francesco Marchesi⁴  Daniela Renzi⁴  Francesco Pisani⁴  Antonio Spadea⁴  Svitlana Gumenyuk⁴  Elena Papa⁴  Atelda Romano⁴  Francesca Palombi⁴  Andrea Mengarelli⁴  Marco Montanaro⁵  Luigi Toma⁶  Anna Ceribelli⁷  Fulvia Pimpinelli⁸  Fabrizio Ensoli⁸  EneaGino Di Domenico⁸  MariaTeresa Gallo⁸  Grazia Prignano⁸  AnnaMarina Liberati⁹  Mirella Marino^1,10 

[1] Clinical Pathology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy;Genomic and Epigenetic Unit, Translational Research Area, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy;Hematology Unit, Tor Vergata University Hospital, Viale Oxford, 81 00133 Rome, Italy;Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy;Hematology, Belcolle Hospital, Str. Sammartinese, 01100 Viterbo, Italy;Infectious Disease Consultant, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy;Medical Oncology, San Camillo de Lellis Hospital, Viale Kennedy, 02100 Rieti, Italy;Molecular Virology, Pathology and Microbiology, IRCCS San Gallicano Dermatological Institute, Via Elio Chianesi, 53 00144 Rome, Italy;Oncology-Hematology, Santa Maria Hospital, University of Perugia, Viale Tristano di Joannuccio, 05100 Terni, Italy;Pathology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy;

关键词: CMV infection;    invasive fungal disease;    gram positive bacteria;    gram negative bacteria;    skin commensals;    autologous stem cell transplant;    multiple myeloma;    lymphoma;   

DOI  :  10.3390/ijms20061373

来源: DOAJ

【 摘 要 】

Unlike allogeneic transplant, autologous stem cell transplantation (ASCT) represents a procedure with a low-risk of cytomegalovirus (CMV) symptomatic reactivation-infection/end-organ disease (CMV complications) and invasive fungal disease (IFD). However, novel drugs for the treatment of lymphoproliferative malignancies could cause an increase of such opportunistic infections, even after ASCT. To the best of our knowledge, there are no published data demonstrating an association between CMV and IFD in the autologous setting, while this association has been widely reported in allogeneic transplantation. We have reviewed our series of 347 ASCT in myeloma and lymphoma patients performed over a period of 14 years with the aim of investigating the descriptive and analytical epidemiology of bacterial, CMV and IFD complications, focusing on the association between CMV and IFD. Patients with myeloma have significantly fewer bacterial infections and IFD than patients with lymphoma, but a similar rate of CMV complications. Descriptive epidemiological data are consistent with the literature, indicating an overall incidence of 36%, 3.5% and 15.5% for bacterial infections, IFD and CMV complications, with a case mortality rate of 4%, 16.7% and 3.7%, respectively. A strong correlation between CMV and IFD exists, with 8 cases of IFD out of a total of 12 presenting a CMV complication. At multivariate analysis, a diagnosis of lymphoma, ≥3 previous treatment lines and age ≥60 years were found to be independent risk factors for IFD. Duration of neutropenia (ANC < 500/mm3) ≥7 days represents an independent risk factor for CMV complications, where neutropenia most likely represents a crude surrogate biomarker indicating a deeper and longer state of overall immunosuppression. From our data we conclude that (1) myeloma patients are at lower risk of bacterial infections and IFD as compared with lymphoma patients but are at equal risk of CMV complications, most likely as a consequence of a selective impact of bortezomib on Herpes Viruses infection control; (2) a significant association exists between CMV and IFD, although a possible cause-effect relationship remains to be determined; (3) IFD is a rare complication after ASCT but burdened by a mortality rate of about 17%, with peak rates in older lymphoma patients who underwent more intensive therapeutic regimens.

【 授权许可】

Unknown