Preventing, Managing Cytomegalovirus Infection in the Setting of Hematopoietic Stem Cell Transplantation

Recently published guidelines on the prevention and management of cytomegalovirus (CMV) infection in patients with hematologic cancers, particularly those undergoing hematopoietic stem cell transplantation (HSCT), provided details regarding the optimal assay for detecting CMV infection/reactivation, as well as antiviral approaches to the prevention and management of CMV in these patients. These guidelines were recently published in Lancet Infectious Diseases.

Cytomegalovirus is a common virus that rarely causes problems in healthy persons. With an estimated real-world incidence of CMV disease at 5% to 10% of those undergoing HSCT, CMV infections in immunocompromised patients can affect multiple organs including the lungs, gastrointestinal tract, eyes, and the central nervous system (CNS), and result in substantial morbidity and mortality. In addition, reactivation of CMV can also occur in patients undergoing HSCT or in those with hematologic cancers being treated with the immunosuppressive drug alemtuzumab or the phosphoinositide 3-kinase inhibitor idelalisib outside of the transplant setting.

Following a meeting in 2017 by the European Conference on Infections in Leukaemia (ECIL 7), guidelines for the management of CMV infection in patients with hematologic cancers were formulated and recently published. 

Recommendations from these guidelines cover approaches to the prevention and diagnosis of CMV infection, as well as the management of CMV disease.

With respect to CMV prevention in patients undergoing allogeneic HSCT, the guidelines committee recommend pretransplant testing of patients and donors for CMV IgG antibodies close to the time of HSCT, as well as selecting a CMV-seronegative donor for a CMV-seronegative patient, whenever possible. Conversely, a CMV-seropositive donor is preferred for CMV-seropositive patients who will undergo allogeneic HCST from an unrelated donor following myeloablative conditioning, given the increased likelihood of CMV reactivation in these patients if the donor is CMV seronegative.

Interestingly, results of several studies have suggested that there is an association between CMV reactivation and a decreased risk of relapse in patients with acute myeloid leukemia (AML). Nevertheless, the guidelines panel recommended against strategies “permissive for CMV reactivation” in these patients, given the limited evidence for, and potential risk of, such an approach.

Another focus of the guidelines is on monitoring patients for CMV following allogeneic HSCT. Specifically, weekly testing of whole blood or plasma using a quantitative polymerase chain reaction (qPCR) assay to detect/measure CMV viral load is recommended for the first 100 days after the transplant, with longer durations of CMV monitoring recommended for populations at higher risk of CMV infection or reactivation. The guidelines committee also suggests that sequential monitoring of interferon-γ-producing CMV-specific T cells could augment information obtained through measurement of CMV viral load.

Regarding strategies to prevent CMV reactivation/disease in CMV-seropositive patients who have undergone allogeneic HSCT, the guideline recommends both chemoprophylaxis with antiviral drugs and preemptive use of these agents only after viral load monitoring indicates CMV reactivation. For example, intravenous (IV) ganciclovir or foscarnet is considered suitable for first-line preemptive therapy.

Antiviral therapy (eg, IV ganciclovir) is recommended for patients with CMV disease. Furthermore,consideration of immunoglobulin or hyperimmune globulin in addition to antiviral therapy for patients with CMV pneumonia is included, among other recommendations, for managing CMV disease.

Guideline-based recommendations for managing patients with CMV infection receiving alemtuzumab include regular CMV viral load monitoring during the period of maximum immunosuppression. Antiviral therapy is also included as an option for some of these patients.

Also recommended is the use of leucocyte-depleted or CMV-seronegative blood products in CMV-seronegative patients receiving idelalisib for hematologic cancers, and to consider antiviral therapy, either preemptively in those with a detectable CMV viral load or for those with symptomatic CMV infection.

Finally, the guideline authors emphasized that managing resistant or refractory CMV infection or disease in patients with hematologic cancers remains an ongoing challenge.

Reference Ljungman P, de la Camara R, Robin C, et al. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7) [published online May 29, 2019]. Lancet Infect Dis. doi: 10.1016/S1473-3099(19)30107-0