Is CMV PCR Monitoring Necessary for Hematological Malignancy during Chemotherapy?

Introduction: Cytomegalovirus (CMV) is an important cause of mortality and morbidity in patients with immune defects. Due to the extensive use of immunosuppressive treatments, CMV infections have emerged as one of the most critical problems for patients with hematological malignancies globally. CMV infections can lead to life-threatening CMV-related diseases and graft rejections after bone marrow transplantation. It is more difficult to determine the incidence and risk factors of CMV infection in non-transplanted patients. The purpose of this study was to evaluate the frequency of CMV reactivation and risk factors of CMV disease in chemotherapy-treated patients who did not get stem cell transplantation.

Materials and Methods: This was a prospective, single-center study involving 316 non-transplanted adult patients receiving chemotherapy for hematologic malignancies. Patients diagnosed with leukemia and lymphoma who developed neutropenia for more than 3 days after chemotherapy were included in the study. After chemotherapy, CMV PCR follow-up was routinely performed 2 days a week during their hospitalization. CMV DNA was investigated by real-time PCR method. CMV-DNA follow-up results and clinical evaluations of the patients were reviewed. The relationship between CMV reactivation and clinical and demographic parameters of the cases was investigated.

Results: There were totally 504 hospitalization episodes of 316 patients. CMV PCR was studied in all hospitalization episodes. CMV infection incidence of 316 patients was 9%. CMV viremia was observed in 35 of 504 hospitalization episodes, and CMV viremia and disease were observed together in 13. Of the 13 episodes with CMV disease, 4 were CMV retinitis and 9 were CMV pneumonia.

Antiviral therapy was given for a total of 29 episodes. Of the 48 episodes with CMV viremia, 16 (33%) received preemptive treatment, while 13 (27%) received treatment for CMV disease. Ganciclovir was given to all patients as preemptive treatment. Ganciclovir was administered as antiviral therapy in 13 episodes with both CMV viremia and CMV disease. 19 episodes (40%) with CMV viremia were followed without antiviral treatment. Of the 29 episodes that received antiviral therapy for CMV viremia, 13 (45%) recovered with antiviral therapy, while 3 (10%) died despite receiving antiviral therapy. PCR positivity continued in 13 (45%) patients, but CMV disease did not develop in these patients during follow-up.

CMV viremia was present in 25 (7%) episodes with a diagnosis of leukemia and 23 (14%) with a diagnosis of lymphoma. There was a significant difference in the frequency of CMV viremia between these two groups (p=0.035). While CMV disease was observed in 5 (2%) episodes with a diagnosis of leukemia, it was found in 8 (5%) episodes with a diagnosis of lymphoma. There was a significant difference in the frequency of CMV disease between these two groups (p=0.038). Both cmv viremia and cmv disease were statistically higher in refractory disease (p=0.006, p=0.016).

In the univariate analysis, diagnosis of lymphoma, refractory disease, administration of >2 lines of chemotherapy, rituximab based therapy, lymphopenia before neutropenia, lymphopenia after neutropenia, and co-infection were independent risk factors for CMV viremia. However, in the multivariate analysis, only post-neutropenia lymphopenia and co-infection status were independent risk factors for CMV viremia. The risk of developing CMV in patients with lymphopenia after neutropenia was 3.1 times higher than those without lymphopenia (p=0.011), and it was 6.4 times higher in those with co-infection than in those without (p=0.013).

Co-infection was seen in 402 (80%) of 504 hospitalization episodes. There was a statistically significant correlation between CMV viremia and co-infection. (p=0.002). However, no significant relationship was found between CMV disease and co-infection (p=0.081).

Conclusion: This real-life experience shows that CMV infection can become a serious threat for patients with hematological malignancies during the period of intensive chemotherapeutic regimen. We think that our study, which reflects the experience of a single center, is important in terms of monitoring CMV in patients with hematological malignancies who did not undergo transplantation.