Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

Abstract

Cytomegalovirus (CMV) infection in clinical settings other than the allogeneic transplant represents a poorly explored issue. Thus, we performed a comprehensive review of the medical literature about CMV infection in patients undergoing autologous hematopoietic stem cell transplant and in other nontransplant-related hematologic patients. In autologous hematopoietic stem cell transplant, a CMV reactivation is reported to occur in up to 41% of CMV seropositive patients, when a prospective monitoring of antigenemia and/or viremia by polymerase chain reaction was adopted. However, more contained frequencies, up to 12%, have been reported when the monitoring criteria were based on a clinically driven diagnostic strategy. The most relevant risk factors appear to be CD34 + selected autografts, total body irradiation, and prior treatment with Alemtuzumab, Fludarabine, or Bortezomib, respectively. Other possible risk factors (ie, prior treatment with Rituximab, T-cell lymphomas, and pretransplant HBcIgG seropositivity) are still debated. In nontransplant settings, the data are very heterogeneous; thus, CMV infection incidence and risk factors are more difficult to establish. Overall, the rate of CMV infection/reactivation ranges between 2 and 67%. High-dose steroids, advanced disease, poor performance status, and treatment with Alemtuzumab, Fludarabine, Bortezomib, and Rituximab appear as the most relevant, though putative, risk factors. Intravenous Ganciclovir represents the gold standard for first-line treatment of CMV infection in these patients. Oral Valganciclovir and Foscarnet are other possible options. Extensive prophylaxis and preemptive therapy are not generally recommended, with the exception of high-risk patients.

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

“…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.…”

“…Given the low rate of patients with CMV-DNAemia that develop a symptomatic CMV infection, prospective monitoring of CMV titers in these patients is not recommended. 3 When CMV-DNA quantification was performed on clinical indication, the rate of symptomatic CMV infection post-ASCT ranges from 0.7% to 30.7%. 3 Bortezomib-containing induction regimens are associated with a higher incidence of CMV reactivation post-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.…”

Cytomegalovirus reactivation after bortezomib treatment for multiple myeloma and light chain amyloidosis

“…A prospective study performed by Marchesi et al (2013) of 80 patients with multiple myeloma treated with ASCT also reported a significantly higher rate of CMV reactivation in patients who received bortezomib and immunomodulatory therapy when compared to standard anthracycline‐based treatment (9.4% vs 1.1% P = .019), but not in patients treated with immunomodulatory therapy alone. The study concluded that patients treated with bortezomib‐based regimens were at higher risk of developing symptomatic CMV reactivation after ASCT . A more recent retrospective study performed by Hasegawa et.al (2016) of 120 patients with multiple myeloma reported a CMV infection rate of 20% and three cases of CMV disease.…”

“…A comprehensive literature review performed by Marchesi et al (2017) of non‐transplant haematology patients revealed highly variable CMV reactivation rates ranging between 2% and 39%, but this included a wide range of agents including bortezomib, bendamustine and rituximab. The CMV reactivation rate of 39% of seropositive patients in this current study is similar to the 48.5% reported by Kim et.al; although these studies are not directly comparable due to different patient populations.…”