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 Mar 19;20(6):1373. doi: 10.3390/ijms20061373.

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; autologous stem cell transplant; gram negative bacteria; gram positive bacteria; invasive fungal disease; lymphoma; multiple myeloma; skin commensals.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Cytomegalovirus Infections / complications*
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Invasive Fungal Infections / complications*
  • Lymphoproliferative Disorders / microbiology*
  • Lymphoproliferative Disorders / virology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Opportunistic Infections / complications*
  • Risk Factors
  • Transplantation, Autologous / adverse effects
  • Young Adult