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

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

doi:10.3390/ijms20061373

Open AccessCommunication

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

by

Francesco Marchesi

^1,*,

Fulvia Pimpinelli

²,

Enea Gino Di Domenico

²

,

Daniela Renzi

¹,

Maria Teresa Gallo

²,

Giulia Regazzo

³,

Maria Giulia Rizzo

³,

Svitlana Gumenyuk

¹,

Luigi Toma

⁴,

Mirella Marino

⁵,

Iole Cordone

⁶,

Maria Cantonetti

⁷,

Anna Marina Liberati

⁸,

Marco Montanaro

⁹,

Anna Ceribelli

¹⁰,

Grazia Prignano

²,

Francesca Palombi

¹,

Atelda Romano

¹,

Elena Papa

¹,

Francesco Pisani

¹,

Antonio Spadea

¹,

William Arcese

⁷,

Fabrizio Ensoli

² and

Andrea Mengarelli

^1,† Show full author list Hide full author list

¹

Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy

²

Molecular Virology, Pathology and Microbiology, IRCCS San Gallicano Dermatological Institute, Via Elio Chianesi, 53 00144 Rome, Italy

³

Genomic and Epigenetic Unit, Translational Research Area, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy

⁴

Infectious Disease Consultant, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy

⁵

Pathology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy

⁶

Clinical Pathology Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi, 53 00144 Rome, Italy

⁷

Hematology Unit, Tor Vergata University Hospital, Viale Oxford, 81 00133 Rome, Italy

⁸

Oncology-Hematology, Santa Maria Hospital, University of Perugia, Viale Tristano di Joannuccio, 05100 Terni, Italy

⁹

Hematology, Belcolle Hospital, Str. Sammartinese, 01100 Viterbo, Italy

¹⁰

Medical Oncology, San Camillo de Lellis Hospital, Viale Kennedy, 02100 Rieti, Italy

^*

Author to whom correspondence should be addressed.

^†

The author is on behalf of the Rome Transplant Network.

Int. J. Mol. Sci. 2019, 20(6), 1373; https://doi.org/10.3390/ijms20061373

Submission received: 11 January 2019 / Revised: 11 March 2019 / Accepted: 14 March 2019 / Published: 19 March 2019

(This article belongs to the Special Issue Host-Cytomegalovirus Interactions: Pro- and Antiviral Key Factors Affecting CMV Infection Outcome or Therapeutic Approaches)

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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.

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

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MDPI and ACS Style

Marchesi, F.; Pimpinelli, F.; Di Domenico, E.G.; Renzi, D.; Gallo, M.T.; Regazzo, G.; Rizzo, M.G.; Gumenyuk, S.; Toma, L.; Marino, M.; et al. Association between CMV and Invasive Fungal Infections After Autologous Stem Cell Transplant in Lymphoproliferative Malignancies: Opportunistic Partnership or Cause-Effect Relationship? Int. J. Mol. Sci. 2019, 20, 1373. https://doi.org/10.3390/ijms20061373

AMA Style

Marchesi F, Pimpinelli F, Di Domenico EG, Renzi D, Gallo MT, Regazzo G, Rizzo MG, Gumenyuk S, Toma L, Marino M, et al. 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. 2019; 20(6):1373. https://doi.org/10.3390/ijms20061373

Chicago/Turabian Style

Marchesi, Francesco, Fulvia Pimpinelli, Enea Gino Di Domenico, Daniela Renzi, Maria Teresa Gallo, Giulia Regazzo, Maria Giulia Rizzo, Svitlana Gumenyuk, Luigi Toma, Mirella Marino, and et al. 2019. "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 20, no. 6: 1373. https://doi.org/10.3390/ijms20061373

APA Style

Marchesi, F., Pimpinelli, F., Di Domenico, E. G., Renzi, D., Gallo, M. T., Regazzo, G., Rizzo, M. G., Gumenyuk, S., Toma, L., Marino, M., Cordone, I., Cantonetti, M., Liberati, A. M., Montanaro, M., Ceribelli, A., Prignano, G., Palombi, F., Romano, A., Papa, E., ... Mengarelli, A. (2019). 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, 20(6), 1373. https://doi.org/10.3390/ijms20061373

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

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