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Table of Contents
EDITORIAL
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 76-77

Cytomegalovirus reactivation in solid tumors: Are we missing the bus (bug)?


1 Division of Infectious Diseases, Rajiv Gandhi Cancer Institute, New Delhi, India
2 Division of Infectious Diseases, Apollo Cancer Institute, Chennai, Tamil Nadu, India

Date of Submission22-Dec-2019
Date of Acceptance04-Jan-2020
Date of Web Publication24-Feb-2020

Correspondence Address:
K Abdul Ghafur
Apollo Cancer Institute, Chennai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_119_19

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How to cite this article:
Bansal N, Ghafur K A. Cytomegalovirus reactivation in solid tumors: Are we missing the bus (bug)?. Cancer Res Stat Treat 2020;3:76-7

How to cite this URL:
Bansal N, Ghafur K A. Cytomegalovirus reactivation in solid tumors: Are we missing the bus (bug)?. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Apr 10];3:76-7. Available from: http://www.crstonline.com/text.asp?2020/3/1/76/279077



Human cytomegalovirus (CMV), a β-herpes virus, is responsible for a broad spectrum of clinical conditions. In immunocompetent hosts, it can cause a self-limiting illness such as infectious mononucleosis or a devastating condition known as congenital CMV syndrome. Similarly, in immunocompromised hosts, CMV may be responsible for asymptomatic CMV viremia or can cause life-threatening infections affecting almost every organ of the body, including brain and lungs.[1] These presentations could be due to fresh infection by CMV virus or reactivation. CMV spreads via various body secretions during close contact; mother to fetus during gestation and via an organ or blood during transplants and transfusions. Once acquired, CMV persists indefinitely in host tissues, and can reactivate when immunosuppression occurs.[1]

Although CMV is known to occur worldwide, it is more common in developing countries. In India, as per the available data, the prevalence of CMV IgG positivity in women of childbearing age has been found to be close to 90%.[2] With the increasing popularity of procedures and therapeutic modalities leading to iatrogenic immunosuppression, the management of CMV infections is a challenge in Indian settings. Classical situations where CMV reactivation is actively looked for are solid organ transplants, hematopoietic stem cell transplants, HIV, and recipients of alemtuzumab (anti-CD52) and/or antithymocyte immunoglobulin.[3],[4],[5] In these situations, hosts are either started on prophylaxis or are on close monitoring after risk stratification. These preemptive/prophylactic strategies have led to significant reduction in mortality and morbidity associated with CMV. Unfortunately, the prevalence of CMV infection and its associated morbidity has not been well studied in solid organ tumors, resulting in a large academic and clinical lacuna. The study done by Agrawal et al.[6] attempts to fill this need by analyzing the manifestations of CMV in solid organ malignancies in the Indian context.

In this, well-conducted, single-center, retrospective study, the authors attempt to study the prevalence and manifestations of CMV in adult patients (>15 years) with solid organ malignancies. This study analyzes the data over a long period of 10 years (2010–2019). The authors used the presence of CMV viremia as the criterion for inclusion in the study. Over the study period, only 17 patients were found to have CMV viremia with a median age of 44 years. Cervical carcinoma was the most common cancer among patients with CMV infection in this study, present in 35% of cases. Diabetes mellitus and HIV were the most common comorbidities accompanying CMV infection. CMV infection was found in various chemotherapy regimens, and no particular regimen had any special predilection to CMV infection. During CMV reactivation, only 45% of patients were found to have neutropenia (absolute neutrophil count <1500/mm3). Concomitant culture positivity by other microorganisms was noted in 71% of patients. Fever was the most common presenting symptom and fever alone (without any localization) was seen in 29% of cases. Pneumonia was the most common clinical syndrome, seen in 41% of cases. CMV viremia was also found in patients presenting with diarrhea, esophagitis, and encephalitis. CMV therapy was given to 59% of cases, with ganciclovir, the drug of choice in all cases. The median duration of antiviral therapy was 14 days, and all patients received concomitant broad-spectrum antibiotic therapy. Overall, 59% survived the acute episode and remaining 41% succumbed to the illness.

Although a very good attempt to study the pattern of CMV in solid malignancies, the article has various limitations. First, routine measurement of CMV viremia was not part of the institute protocol in solid organ malignancies, so the exact prevalence of CMV disease could not be established. Second, the mere presence of CMV in blood does not establish it as the etiological agent of the disease presentation. The presence of CMV inclusion bodies or measurement of CMV in the relevant tissue sample indicates end-organ disease. Unfortunately, tissue biopsy was not available in any of the patients. Third, it would have been better if all these 17 patients were closely followed up to look for secondary reactivation. As this study was a retrospective analysis, understandably, the authors could not follow-up the patients. Fourth, all patients received a broad-spectrum anti-infective agent along with ganciclovir, so any conclusion made on outcomes may not be accurate. Finally, as the authors themselves have stated that the numbers are too low and it is a single-center study, conclusions made may not have broader applications.

CMV is a well-established reason for various presentations in patients with hematological malignancies. However, there are limited data of the same in solid organ tumors. In another retrospective study, 17 out of 107 patients with CMV viremia had solid organ tumors, of which eight patients had relevant clinical CMV disease.[7] In a study done by Kou et al., 15 patients with positive CMV IgG were followed up during their chemotherapy.[8] All of these patients except one had solid organ tumors. All except one patient experienced CMV reactivation during the course of chemotherapy, with the average viral load peaking after the third cycle of treatment. Clinical symptoms attributable to CMV infection were seen as the viral load increased. It was concluded that the incidence of CMV reactivation is high and reactivation is not asymptomatic, but self-limiting in most cases.[8] In another retrospective analysis, among patients with CMV viremia done in Taiwan, 70% of patients had solid tumors and the overall mortality rate was close to 56%.[9] Mechanical ventilation, presence of leukocytosis, and lack of appropriate early treatment were independent factors associated with a higher mortality rate. The authors of this study even concluded that preemptive therapy in these patients may lead to better prognosis.[9]

The study by Agrawal et al.[6] is probably the first study on CMV infection in solid tumors from India and provides a 'real-world' picture of the CMV disease in this group of patients. Even though we cannot derive a policy statement based on the study, given its shortcomings, it does carve out a path for future research. With the increasing use of various immune checkpoint inhibitors such as nivolumab and ipilimumab, CMV could turn out to be much more challenging than it used to be.[10] Hence, it is prudent not only to report the incidence of CMV infection, but also to conduct prospective research to establish the risk factors for CMV reactivation and define the magnitude of the problem, so that clear preemptive and prophylactic strategies are put in place to prevent us and our patients from missing the bus (bug).



 
  References Top

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Clyde S, Crumpacker II. Cytomegalovirus (CMV). In: Mandell GL, Bennett JE, Dolin R, editors. Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, USA: Elsevier Churchill Livingstone; 2015. p. 1738-54.  Back to cited text no. 1
    
2.
Chakravarti A, Kashyap B, Matlani M. Cytomegalovirus infection: An Indian perspective. Indian J Med Microbiol 2009;27:3-11.  Back to cited text no. 2
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3.
Camille NK, Martin SH. Cytomegalovirus and human herpes virus type 6, 7 and 8. In: Kasper DL, Fauci AS, Hauser SL, editors. Harrison's Principles of Internal Medicine. 19th ed. USA: McGraw Hill Education; 2015. p. 1190-94.  Back to cited text no. 3
    
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Ramanan P, Razonable RR. Cytomegalovirus infections in solid organ transplantation: A review. Infect Chemother 2013;45:260-71.  Back to cited text no. 4
    
5.
Rossini F, Terruzzi E, Cammarota S, Morini F, Fumagalli M, Verga L, et al. Cytomegalovirus infection after autologous stem cell transplantation: Incidence and outcome in a group of patients undergoing a surveillance program. Transpl Infect Dis 2005;7:122-5.  Back to cited text no. 5
    
6.
Agrawal AK, Akhil R, Noronha V, Joshi A, Patil V, Menon N, et al. Cytomegalovirus infection in solid malignancies. Cancer Res Stat Treat 2020;3:19-24.  Back to cited text no. 6
  [Full text]  
7.
Schlick K, Grundbichler M, Auberger J, Kern JM, Hell M, Hohla F, et al. Cytomegalovirus reactivation and its clinical impact in patients with solid tumors. Infect Agent Cancer 2015;10:45.  Back to cited text no. 7
    
8.
Kuo CP, Wu CL, Ho HT, Chen CG, Liu SI, Lu YT. Detection of cytomegalovirus reactivation in cancer patients receiving chemotherapy. Clin Microbiol Infect 2008;14:221-7.  Back to cited text no. 8
    
9.
Wang YC, Wang NC, Lin JC, Perng CL, Yeh KM, Yang YS, et al. Risk factors and outcomes of cytomegalovirus viremia in cancer patients: A study from a medical center in northern Taiwan. J Microbiol Immunol Infect 2011;44:442-8.  Back to cited text no. 9
    
10.
Franklin C, Rooms I, Fiedler M, Reis H, Milsch L, Herz S, et al. Cytomegalovirus reactivation in patients with refractory checkpoint inhibitor-induced colitis. Eur J Cancer 2017;86:248-56.  Back to cited text no. 10
    




 

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