Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation

Abstract

Cytomegalovirus (CMV) is an agent of global infection, and its acquisition in a population is characterized by an age-dependent rise in seropositivity. After primary infection, CMV remains in the host cells in latent form, and it can reactivate in the case of immune suppression. The risk of CMV recurrence is dependent on the level of incompetency of the immune system, manifested as an impairment of T-cell immunity, including the presence and function of CMV-specific cytotoxic T lymphocytes. This article presents data on the incidence of CMV recurrence in groups of immunocompromised patients, including allogeneic hematopoietic stem cell transplantation (HSCT) patients and other groups of patients, based on a summary of reported data. The median rate of CMV recurrence in HSCT recipients was estimated as 37% after allogeneic transplant and 12% after autologous transplant, 5% in patients with nontransplant hematological malignancies, 14% in recipients of anti-CD52 therapy, 30% in solid organ transplant recipients, 21% in patients with primary immunodeficiencies, 20% during active replication in HIV-positive patients and 3.3% during antiretroviral therapy, 7% in patients with chronic kidney disease, 0.6% in patients with congenital infection, and 0.6% in neonates with primary infection. The highest risk of CMV recurrence and CMV disease is reported for HSCT CMV-seropositive recipients, regardless of donor serostatus. The odds ratio (OR) for CMV recurrence is higher for recipient-positive versus recipient-negative CMV serostatus transplants (OR 8.0), donor-negative/recipient-positive versus donor-positive/recipient-positive CMV serostatus transplants (OR 1.2), unrelated/mismatched versus matched-family donor transplants (OR 1.6), and acute graft-versus-host-disease versus other diseases (OR 3.2). Other risk factors have minor significance.

Cytomegalovirus Reactivation in a Patient With Extensively Pretreated Multiple Myeloma During Daratumumab Treatment

“…The risk of recurrent CMV infection is increased in immunocompromised patients, such as patients with primary immunodeficiencies or HIV infection, solid organ transplant recipients, and patients on hemodialysis. 2 In patients with hematologic disorders, the risk of CMV infection is markedly increased following allogeneic stem cell transplantation or autologous stem cell transplantation (ASCT) with CD34 þ -selected cells, as well as following treatment with high-dose corticosteroids, alemtuzumab, cladribine, or fludarabine, as a result of lower levels and dysfunction of natural killer (NK) cells, CD8 þ T-cells, and CD4 þ T-cells. [2][3][4] Patients with MM have increased susceptibility to infections as a result of myeloma-induced immune dysfunction, including impaired T-and NK-cell activity, and decreased polyclonal immunoglobulin production, as well as cumulative immunosuppression of anti-MM treatment regimens.…”

“…2 In patients with hematologic disorders, the risk of CMV infection is markedly increased following allogeneic stem cell transplantation or autologous stem cell transplantation (ASCT) with CD34 þ -selected cells, as well as following treatment with high-dose corticosteroids, alemtuzumab, cladribine, or fludarabine, as a result of lower levels and dysfunction of natural killer (NK) cells, CD8 þ T-cells, and CD4 þ T-cells. [2][3][4] Patients with MM have increased susceptibility to infections as a result of myeloma-induced immune dysfunction, including impaired T-and NK-cell activity, and decreased polyclonal immunoglobulin production, as well as cumulative immunosuppression of anti-MM treatment regimens. 5 The incidence of CMV DNAemia, defined as presence of CMV-DNA without CMVrelated symptoms, 1 and CMV disease in patients with MM are best studied following ASCT.…”

“…Because of persisting fever, additional diagnostic tests were performed. Repeated laboratory examinations showed no abnormalities, and there was no evidence for mycobacterial disease or respiratory viruses (influenza virus A/B, metapneumovirus, respiratory syncytial virus, parainfluenza virus [types [1][2][3][4], rhinovirus, and coronavirus). A computed tomography scan of the chest and abdomen, as part of the diagnostic workup of fever of unknown origin, revealed no explanation for her symptoms.…”

Aktualitások a sérült immunitású betegek cytomegalovirusinfekcióinak ellátásában. I. Epidemiológia és klinikai szempontok

“…Ebben az esetben ugyanis az eredeti vírusinfekciót kontrolláló vírusspecifikus T-sejteket a kondicionálókezelés eliminálja, a beültetett új immunrendszer a hCMV-naivitása folytán viszont ezt a funkciót nem lesz képes helyettesíteni. Természetesen hCMV-infekció bármely fél pozitivitása esetén előfordul, az incidencia egyedül a D-/R-konstellációban alacsony (3,1%) [42].…”

“…Ilyen többek között az idegen (nem családi) vagy nem HLA-egyező, illetve női donor, a magas víruskópiaszám, az akut és krónikus GvHD. A gyakoriság -serostatustól függően -0,2-14,5% között változhat (Styczynski, 2018) [42]. A GvHD és a hCMVinfekció kedvezőtlen kölcsönhatást gyakorol egymás gyakoriságára és súlyosságára [43].…”