Association between CMV and invasive fungal infections after autologous stem cell transplant in lymphoproliferative malignancies: Opportunistic partnership or cause-effect relationship?

Francesco Marchesi, Fulvia Pimpinelli, Enea Gino Di Domenico, Daniela Renzi, Maria Teresa Gallo, Giulia Regazzo, Maria Giulia Rizzo, Svitlana Gumenyuk, Luigi Toma, Mirella Marino, Iole Cordone, Maria Cantonetti, Anna Marina Liberati, Marco Montanaro, Anna Ceribelli, Grazia Prignano, Francesca Palombi, Atelda Romano, Elena Papa, Francesco PisaniAntonio Spadea, William Arcese, Fabrizio Ensoli, Andrea Mengarelli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number6
DOIs
Publication statusPublished - Mar 2 2019

Keywords

  • Autologous stem cell transplant
  • CMV infection
  • Gram negative bacteria
  • Gram positive bacteria
  • Invasive fungal disease
  • Lymphoma
  • Multiple myeloma
  • Skin commensals

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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