Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation: a case-control study

Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation: a case-control study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation: a case-control study Jinyoung Yang, Young Ho Lee, Jae-Hoon Ko, Kyungmin Huh, Sun Young Cho, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2744306/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Backgrounds: This study aims to evaluate the risk factors and prognosis for CMV diseases in hematologic malignancy patients without HSCT. Methods: We performed a case-control study (1:2) between 2012 and 2022. Adults with pathologic-confirmed CMV diseases (n=60) among hematologic malignancy patients were matched and compared to whom without CMV disease. Results: Lymphoma was the most common underlying malignancy, and gastrointestinal tract involvement was the most common CMV disease. In the case group, high-dose steroid administration and transfusion within one month before diagnosis were higher (p<0.001). Steroid administration (aOR=5.78; 95% confidence interval: 1.25–26.68, p=0.024), red blood cell transfusion within one month (aOR=14.63; 2.75–77.76, p=0.002), low BMI (aOR=13.46, 2.07–87.45, p=0.006), and hypoalbuminemia (aOR=26.48, 5.93–118.17, p<0.001) were independent risk factors associated with CMV disease. The 30-day mortality was higher in the case group and CMV disease was significantly associated with all-cause mortality (aOR=14.41, 3.23–64.31, p<0.001). Conclusions: In hematologic malignancy patients without HSCT, risk factors for CMV organ disease included high-dose steroid administration and RBC transfusion within one month, low BMI, and hypoalbuminemia. Overall mortality was significantly higher with CMV disease, and CMV disease occurrence was a significant risk factor for mortality. Cytomegalovirus CMV organ disease hematologic malignancy hematopoietic stem-cell transplantation Figures Figure 1 Introduction Human cytomegalovirus (CMV) is an opportunistic pathogen, with most infections occurring in immunocompromised hosts such as organ transplant recipients and people with human immunodeficiency virus (HIV) infection, posing significant morbidity and mortality [ 1 ]. Risk factors for CMV infection in patients who underwent hematopoietic stem-cell transplantation (HSCT) are well-known. Because adaptive T-cell responses are important for keeping the virus inactive, restoration of CD4 and CD8 cells after HSCT are critical for virus control [ 2 ]. The most important risk factors for CMV diseases in allogeneic HSCT are the serological statuses of donor and recipient [ 3 ], followed by long-term high-dose corticosteroid exposure, graft-versus-host disease (GVHD), and use of mismatched or unrelated donors [ 4 ]. Additionally, because CMV is cell-associated and transmitted by latent virus reactivation in white blood cells (WBCs), blood transfusions have been suggested as a risk factor for CMV infection [ 5 ], and use of alemtuzumab, an anti-CD52 monoclonal antibody used for T-cell depletion after allogeneic transplantation is a well-known risk factor for CMV infections [ 6 , 7 ]. In autologous HSCT, high-dose corticosteroids, total body irradiation, and inclusion of fludarabine in the conditioning regimen are also potential risk factors for CMV diseases [ 8 ]. Previous studies regarding risk factors for CMV diseases have mainly been conducted on HSCT patients, and risk factors for CMV diseases in hematologic malignancy patients without HSCT have not been formally assessed. Therefore, we performed a study to systematically assess the risk factors, clinical outcomes and impacts on mortality for CMV diseases in hematologic malignancy patients who have not received HSCT. Methods Study Design and Patient Selection This is a retrospective, single-center, 1:2 matched case-control study of CMV organ diseases diagnosed between January 2012 and July 2022. We included patients ≥ 18 years of age at Samsung Medical Center (Seoul, Korea), a 1,989-bed tertiary care university-affiliated hospital and referral center. Patients who underwent HSCT prior to diagnosis of CMV diseases were excluded. For the purposes of risk-factor analysis, matched control subjects were obtained and two control subjects were included for each case patient with CMV disease. The control subjects were matched for the same type of hematologic malignancy diagnosed at a similar time to consider the natural course of the underlying diseases. Definitions and Data Collection Because the definition for CMV diseases was mainly established in transplant recipients, previous guidelines were used for this study [ 9 ]. Only histologically confirmed cases were selected to focus on risk factors and outcomes of patients with definite diagnosis of CMV end-organ diseases. “CMV end-organ disease” was defined as the presence of appropriate clinical symptoms and/or signs with documentation of CMV in tissue from the relevant organ by histopathology, immunohistochemistry, virus isolation, or culture. Immunohistochemistry staining was performed with monoclonal antibodies directed against CMV immediate early nuclear protein and early nuclear protein (Clones CCH2 + DDG9; DAKO, Glostrup, Denmark). Data were systematically collected from the electronic medical records. For the case patients, “time of diagnosis” was defined as the time of CMV diagnosis with pathologic confirmation; for the control subjects, the time of CMV disease in the corresponding case patient was used. Variables analyzed for both case patients and control subjects included demographic characteristics, laboratory data, CMV antigenemia at time of diagnosis, type of involved organ that was pathologically confirmed, chemotherapy regimen, high-dose corticosteroid administration (≥ 20 mg per day of prednisolone for ≥ 2 weeks, equivalent or more) and transfusion within one month before diagnosis. Treatment failure, which was defined as death from CMV disease or recurrence in the same organ after treatment initiation, and all-cause mortality were investigated. We obtained ethical approval from the institutional review board of Samsung Medical Center (SMC 2022-06-099-001) and informed consent was waived as a retrospective study. Statistical Analysis To evaluate the differences between the two patient groups, Student’s t-test and the Mann-Whitney U-test were used to compare continuous variables, and chi-square test and Fisher’s exact test were used to compare categorical variables. We used a multivariable logistic regression model to identify risk factors for CMV disease and overall mortality. All p-values were 2-tailed, and those < 0.05 were considered statistically significant. SPSS 27.0 (IBM, Armonk, NY, USA) was used for all statistical analyses. Results A total of 60 patients with hematologic malignancy and who were diagnosed with CMV diseases, excluding those who underwent allogeneic HSCT, were identified among hospitalized patients at Samsung Medical Center from January 2012 through July 2022. The most common underlying disease was lymphoma (n = 49, 81.7%), and the most common site of infection was the gastrointestinal tract (n = 48, 80%). There were no statistical differences in demographics (Table 1 ) other than body-mass index (BMI). At the time of CMV disease diagnosis, anemia, thrombocytopenia, and hypoalbuminemia were significantly higher in the case group than in the control. In the case group, high-dose corticosteroid administration and transfusion history within one month before diagnosis were significantly higher. Table 1 Baseline characteristics of hematologic malignancy patients with CMV organ disease and matched controls Variables Case (N = 60) Control (N = 120) p-value N (%) or mean ± SD or median (IQR) Age, year 60.25 ± 13.41 58.05 ± 15.77 0.3558 Male sex 29 (48.3%) 74 (61.7%) 0.0883 BMI, kg/m 2 21.30 ± 3.39 24.40 ± 3.94 < 0.0001 Hematologic malignancy Lymphoma 49 (81.7%) 98 (81.7%) Leukemia 9 (15%) 18 (15%) Multiple myeloma 2 (3.3%) 4 (3.3%) CMV organ disease Upper GI tract 22 (36.7%) Lower GI tract 26 (43.3%) Pneumonia 13 (21.7%) Lymphadenitis 2 (3.3%) Laboratory tests WBC, x10 3 /µL 5.54 (2.74–9.00) 5.18 (4.05–6.48) 0.7163 ANC, x10 3 /µL 3.72 (1.92–8.36) 2.66 (2.05–3.67) 0.049 ALC, x10 3 /µL 0.40 (0.18–0.97) 1.56 (1.15–2.01) 0.3361 Hemoglobin, g/dL 8.9 (7.9–10.0) 12.8 (11.1–14.0) < 0.0001 Platelet, x10 3 /µL 71.0 (29.0–170.0) 186.0 (124.5–236.0) < 0.0001 Albumin, g/dL 2.9 (2.6–3.2) 4.3 (4.0–4.6) < 0.0001 Total bilirubin, mg/dL 0.60 (0.40–1.28) 0.50 (0.40–0.80) 0.0091 ESR, mm/h 18.00 (4.25–38.75) 39.00 (10.00–55.00) 0.1186 C-reactive protein, mg/dL 2.80 (1.11–6.77) 0.70 (0.15–3.16) 0.2829 CMV antigenemia, per 200,000 WBCs 4 (0, 53.5) Chemotherapy regimen within 1 month Rituximab included 20 (33.3%) 11 (9.2%) < 0.001 Steroid administration within 1 month 48 (80.0%) 21 (17.5%) < 0.001 Red blood cell transfusion 52 (86.7%) 11 (9.2%) < 0.001 Platelet transfusion 40 (66.7%) 11 (9.2%) < 0.001 Fresh frozen plasma/cryoprecipitate transfusion 13 (21.7%) 0 (0) < 0.001 Outcome Treatment failure 18 (30.0%) 30-day mortality 15 (25.0%) 1 (0.8%) < 0.001 Abbreviations: SD, standard deviation; IQR, interquartile range; CMV, cytomegalovirus; BMI, body-mass index; GI, gastrointestinal; WBC, white blood cell; ANC, absolute neutrophil count; ALC, absolute lymphocyte count Multivariable analysis was performed to determine risk factors for development of CMV diseases (Table 2). After fitting a conditional logistic regression model, low BMI (BMI <23) and hypoalbuminemia (albumin <3.5) significantly increased the risk of developing CMV organ disease. If there was a history of high-dose corticosteroid administration or RBC transfusion within one month, CMV disease incidence increased 5.78 times and 14.63 time, respectively. Table 2. Multivariable analysis of risk factors for development of CMV organ disease Adjusted analysis Risk factor aOR (95% CI) p-value Low BMI (BMI <23) 13.46 (2.07–87.45) 0.006* Steroid within 1 month 5.78 (1.25–26.68) 0.024* RBC transfusion within 1 month 14.63 (2.75–77.76) 0.002* WBC 0.22 (0.04–1.18) 0.077 ANC 5.15 (0.79–33.60) 0.087 ALC 4.47 (0.84–23.68) 0.079 Hypoalbuminemia (albumin <3.5) 26.48 (5.93–118.17) <0.001* Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; BMI, body-mass index; RBC, red blood cell; ANC, absolute neutrophil count; ALC, absolute lymphocyte count All patients with CMV diseases, except one receiving oral valganciclovir, received IV ganciclovir for CMV treatment. The overall treatment failure rate of patients with CMV diseases was 30%, and the 30-day mortality after diagnosis of CMV disease was significantly higher in the case group than in the control. A multivariable analysis showed that development of CMV diseases was significantly associated with all-cause mortality (Table 3). Figure 1 shows the survival curve from the time of CMV diagnosis to July, 2022, for both groups. 90% of the case group and 21 patients died during the follow-up period. The mortality of patients with CMV disease was significantly higher, suggesting that the prognosis of CMV diseases in hematologic malignancy patients was poor. Table 3. Multivariable analysis of risk factors for all-cause mortality Adjusted analysis Risk factor aOR (95% CI) p-value Male sex 5.93 (1.81–19.47) 0.003* RBC transfusion within 1 month 47.24 (1.60–1393.70) 0.026* PLT transfusion within 1 month 0.03 (0.00–1.09) 0.056 Hb 0.74 (0.57–0.96) 0.023* PLT 0.99 (0.99–1.00) 0.044* CMV disease 14.41 (3.23–64.31) <0.001* Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; RBC, red blood cell; PLT, platelet; Hb, hemoglobin; CMV, cytomegalovirus Discussion To the best of our knowledge, this is the first matched case-control study to evaluate risk factors for developing CMV organ disease in hematologic malignancy patients who did not receive HSCT. We determined that low BMI, corticosteroid use, prior RBC transfusion, and hypoalbuminemia were independent risk factors for CMV diseases. Such variables have biological plausibility and did not differ significantly from previous studies results for HSCT patients [4, 5]. In previous research from our center regarding CMV colitis in immunocompetent patients, steroid administration and RBC transfusion history were also identified as risk factors [10]. In a recent study of 6,837 Korean women between the ages of 15 and 49, CMV IgG seroprevalence was 95.8% [11]. Another previous study including 710 liver transplantation recipients in Korea reported all patients to be seropositive [12], and it could be concluded, that most cases in this study are reactivations rather than primary infections, although they did not test for CMV-specific antibody. The strength of our study is that it expanded study subject inclusion relative to previous studies that mainly focused on HSCT to also include patients with hematologic malignancies who did not receive HSCT. It could be assumed that GI-involved disease was the most common in our study because biopsy is relatively easy to perform for the GI tract. However, stringent patient selection was made by including only pathologically confirmed patients. We also found that CMV organ disease was a predictor of poor prognosis even in hematologic malignancy patients who did not receive HSCT. This study has several limitations. First, because this study was a retrospective study, it is not possible to know the causal relationship between the revealed risk factors. Therefore, a prospective study is further needed. Second, the number of included cases was relatively small (n=60). However, we tried to overcome this disadvantage by performing a matched case-control study (1:2 ratio). Third, only pathologically confirmed cases were included for definitive diagnosis. Thus, a selection bias may have occurred due to the exclusion of patients who did not undergo biopsy. Fourth, although the CMV antigenemia test is more labor-intensive and does not have a standardization assay [14], it is more frequently used than PCR test for CMV-DNA in our institution because of cost issues. However, the antigenemia test was difficult to perform in hematologic malignancy patients who have profound neutropenia. Therefore, the usefulness of CMV antigenemia could not be evaluated in this study. Finally, it was difficult to evaluate the risk of specific drugs because the types of hematologic malignancies included in this study and the treatment medications were diverse. Previous studies found that dasatinib, which suppresses T-cell activation and proliferation, when administered to chronic myeloid leukemia patients, may be a potential risk factor for CMV reactivation, but further research is needed on other anti-cancer drugs [15, 16]. In conclusion, we formally assessed the risk factors for development of CMV organ diseases in hematologic malignancy patients without HSCT, showing that high-dose corticosteroid, RBC transfusion within one month, low BMI, and hypoalbuminemia are independent risk factors. Furthermore, overall mortality was significantly higher when CMV disease occurred, and the occurrence of CMV disease was found to be a significant risk factor for mortality. Abbreviations CMV: cytomegalovirus HIV: human immunodeficiency virus HSCT: hematopoietic stem-cell transplantation GVHD: graft-versus-host disease BMI: body-mass-index Declarations Ethics approval and consent to participate This study was approved by the institutional review board of Samsung Medical Center (SMC 2022-06-099-001) and informed consent was waived as a retrospective study. All experiments were performed in accordance with relevant guidelines and regulations (such as the Declaration of Helsinki). Consent for publication Not applicable Avilability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that there is no conflict of interest. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors’ con tributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jinyoung Yang, Young Ho Lee, Jaehoon Ko, Kyungmin Huh, Cheol-In Kang. The first draft of the manuscript was written by Jinyoung Yang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledements Not applicable Author information Jinyoung Yang, [email protected] Young Ho Lee, [email protected] Jae-Hoon Ko, [email protected] Kyungmin Huh, [email protected] Sun Young Cho, [email protected] Doo Ryeon Chung, [email protected] Kyong Rak Pcek, [email protected] Chul Won Jung, [email protected] Cheol-In Kang, [email protected] References Alonso-Álvarez S, Colado E, Moro-García MA, Alonso-Arias R. Cytomegalovirus in Haematological Tumours.Front Immunol. 2021 Oct18;12:703256. doi: 10.3389/fimmu.2021.703256 . Boeckh M, Geballe AP. Cytomegalovirus: pathogen, paradigm, and puzzle. J Clin Invest. 2011 May;121(5):1673–80. 10.1172/JCI45449 . Pande A, Dubberke ER. Cytomegalovirus Infections of the Stem Cell Transplant Recipient and Hematologic Malignancy Patient. Infect Dis Clin North Am. 2019 Jun;33(2):485–500. doi: 10.1016/j.idc.2019.02.008 . Epub 2019 Mar 30. Boeckh M, Nichols WG, Papanicolaou G, Rubin R, Wingard JR, Zaia J. Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003 Sep;9(9):543–58. 10.1016/s1083-8791(03)00287-8 . Barbara JA, Tegtmeier GE. Cytomegalovirus and blood transfusion. Blood Rev. 1987 Sep;1(3):207–11. 10.1016/0268-960x(87)90037-3 . Chakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O'Gorman P et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution.Blood. 2002 Jun15;99(12):4357–63. doi: 10.1182/blood.v99.12.4357 . Chae YS, Sohn SK, Kim JG, Cho YY, Moon JH, Yang DH et al. Impact of alemtuzumab as conditioning regimen component on transplantation outcomes in case of CMV-seropositive recipients and donors.Am J Hematol. 2008Aug;83(8):649–53. doi: 10.1002/ajh.21215 . Holmberg LA, Boeckh M, Hooper H, Leisenring W, Rowley S, Heimfeld S et al. Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation.Blood. 1999 Dec15;94(12):4029–35. Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G et al. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017 Jan 1;64(1):87–91. doi: 10.1093/cid/ciw668 . Epub 2016 Sep 28. Ko JH, Peck KR, Lee WJ, Lee JY, Cho SY, Ha YE et al. Clinical presentation and risk factors for cytomegalovirus colitis in immunocompetent adult patients.Clin Infect Dis. 2015 Mar15;60(6):e20-6. doi: 10.1093/cid/ciu969 . Epub 2014 Dec 1. Choi R, Lee S, Lee SG, Lee EH. Seroprevalence of CMV IgG and IgM in Korean women of childbearing age.J Clin Lab Anal. 2021 Apr;35(4):e23716. doi: 10.1002/jcla.23716 . Epub 2021 Mar 30. Kim JM, Kim SJ, Joh JW, Kwon CH, Shin M, Kim EY et al. Early and delayed onset cytomegalovirus infection of liver transplant recipients in endemic areas. Transplant Proc. 2010 Apr;42(3):884-9. doi: 10.1016/j.transproceed.2010.02.025 . O'Brien S, Ravandi F, Riehl T, Wierda W, Huang X, Tarrand J et al. Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy.Blood. 2008 Feb15;111(4):1816–9. doi: 10.1182/blood-2007-03-080010 . Epub 2007 Nov 26. Hong SI, Kim T, Park SY, Jung J, Lee JY, Chong YP, et al. Sensitivity of the Cytomegalovirus Antigenemia Assay to Diagnose Cytomegalovirus Retinitis. Infect Chemother. 2016 Dec;48(4):302–8. 10.3947/ic.2016.48.4.302 . Epub 2016 Nov 22. Choi JK, Cho SY, Choi SM, Kim GH, Lee SE, Lee S, et al. Cytomegalovirus Colitis during Dasatinib Treatment for Patients with Hematologic Malignancy: Case Series and Literature Review. Infect Chemother. 2018 Jun;50(2):153–9. 10.3947/ic.2018.50.2.153 . Kreutzman A, Ladell K, Koechel C, Gostick E, Ekblom M, Stenke L et al. Expansion of highly differentiated CD8 + T-cells or NK-cells in patients treated with dasatinib is associated with cytomegalovirus reactivation.Leukemia. 2011Oct;25(10):1587–97. doi: 10.1038/leu.2011.135 . Epub 2011 Jun 7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2744306","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":189976113,"identity":"a5b12b92-7408-47a8-9906-fdb4ca6c43d4","order_by":0,"name":"Jinyoung Yang","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jinyoung","middleName":"","lastName":"Yang","suffix":""},{"id":189976114,"identity":"3d66ff1e-721c-498a-87e5-84f86a91a0be","order_by":1,"name":"Young Ho Lee","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Young","middleName":"Ho","lastName":"Lee","suffix":""},{"id":189976115,"identity":"3060bcc3-6dbc-4347-861f-dd23865b91cb","order_by":2,"name":"Jae-Hoon Ko","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jae-Hoon","middleName":"","lastName":"Ko","suffix":""},{"id":189976116,"identity":"f2b9897f-9c69-4a24-b045-f8e826b59a2c","order_by":3,"name":"Kyungmin Huh","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kyungmin","middleName":"","lastName":"Huh","suffix":""},{"id":189976118,"identity":"3cf42765-f870-47f1-8b40-03ff02bdadb0","order_by":4,"name":"Sun Young Cho","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sun","middleName":"Young","lastName":"Cho","suffix":""},{"id":189976119,"identity":"e26ef6a7-d129-476f-85af-21732b57ac9c","order_by":5,"name":"Doo Ryeon Chung","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Doo","middleName":"Ryeon","lastName":"Chung","suffix":""},{"id":189976121,"identity":"b279fe5b-8e2f-4026-bb1f-60005354c0e1","order_by":6,"name":"Kyong Ran Peck","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kyong","middleName":"Ran","lastName":"Peck","suffix":""},{"id":189976122,"identity":"7357f530-d8d2-4540-af7a-94d9d60dd630","order_by":7,"name":"Chul Won Jung","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chul","middleName":"Won","lastName":"Jung","suffix":""},{"id":189976124,"identity":"81226682-5ff2-42de-9dbf-efc603f960d8","order_by":8,"name":"Cheol-In Kang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYFAC5sYDDAwSDPwSYJ6EDBFaGBvAWiRnAFlABg+xWhgYDG6AtTAQ1sLf3thw4EeNRZ7x7ebjj27UWPAwsB8+ugGfFokzBxsO9hyTKDa7cyyxOecY0GE8aWk38GkxkEhsOMDbIJG47UaOYXMOG1CLBI8ZQS0H/wK1bJ4B0vKPSC2HQbZskABqyW0jQgvIL4dljkkkzriRljg7t0+Ch42QX/jbmw8+fFNTl9g/I/nA55xvdXL87IeP4dWCCdhIUz4KRsEoGAWjABsAAD4XS3umKH0YAAAAAElFTkSuQmCC","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Cheol-In","middleName":"","lastName":"Kang","suffix":""}],"badges":[],"createdAt":"2023-03-28 01:29:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2744306/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2744306/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":35546273,"identity":"a87afb4f-6281-4005-9915-e23a8083cc4f","added_by":"auto","created_at":"2023-04-10 18:00:04","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":26173,"visible":true,"origin":"","legend":"\u003cp\u003eThe survival curve from the time of CMV disease diagnosis.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2744306/v1/b6ef8f67416247643bba8ad5.jpg"},{"id":38084527,"identity":"21a08d61-d99d-45bf-88d5-424378f65e06","added_by":"auto","created_at":"2023-06-06 11:14:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":302871,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2744306/v1/01c5bf83-4c15-459e-b06a-19f66e17acd3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation: a case-control study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHuman cytomegalovirus (CMV) is an opportunistic pathogen, with most infections occurring in immunocompromised hosts such as organ transplant recipients and people with human immunodeficiency virus (HIV) infection, posing significant morbidity and mortality [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Risk factors for CMV infection in patients who underwent hematopoietic stem-cell transplantation (HSCT) are well-known. Because adaptive T-cell responses are important for keeping the virus inactive, restoration of CD4 and CD8 cells after HSCT are critical for virus control [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The most important risk factors for CMV diseases in allogeneic HSCT are the serological statuses of donor and recipient [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], followed by long-term high-dose corticosteroid exposure, graft-versus-host disease (GVHD), and use of mismatched or unrelated donors [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Additionally, because CMV is cell-associated and transmitted by latent virus reactivation in white blood cells (WBCs), blood transfusions have been suggested as a risk factor for CMV infection [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and use of alemtuzumab, an anti-CD52 monoclonal antibody used for T-cell depletion after allogeneic transplantation is a well-known risk factor for CMV infections [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In autologous HSCT, high-dose corticosteroids, total body irradiation, and inclusion of fludarabine in the conditioning regimen are also potential risk factors for CMV diseases [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePrevious studies regarding risk factors for CMV diseases have mainly been conducted on HSCT patients, and risk factors for CMV diseases in hematologic malignancy patients without HSCT have not been formally assessed. Therefore, we performed a study to systematically assess the risk factors, clinical outcomes and impacts on mortality for CMV diseases in hematologic malignancy patients who have not received HSCT.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Patient Selection\u003c/h2\u003e \u003cp\u003eThis is a retrospective, single-center, 1:2 matched case-control study of CMV organ diseases diagnosed between January 2012 and July 2022. We included patients\u0026thinsp;\u0026ge;\u0026thinsp;18 years of age at Samsung Medical Center (Seoul, Korea), a 1,989-bed tertiary care university-affiliated hospital and referral center. Patients who underwent HSCT prior to diagnosis of CMV diseases were excluded. For the purposes of risk-factor analysis, matched control subjects were obtained and two control subjects were included for each case patient with CMV disease. The control subjects were matched for the same type of hematologic malignancy diagnosed at a similar time to consider the natural course of the underlying diseases.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions and Data Collection\u003c/h2\u003e \u003cp\u003eBecause the definition for CMV diseases was mainly established in transplant recipients, previous guidelines were used for this study [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Only histologically confirmed cases were selected to focus on risk factors and outcomes of patients with definite diagnosis of CMV end-organ diseases. \u0026ldquo;CMV end-organ disease\u0026rdquo; was defined as the presence of appropriate clinical symptoms and/or signs with documentation of CMV in tissue from the relevant organ by histopathology, immunohistochemistry, virus isolation, or culture. Immunohistochemistry staining was performed with monoclonal antibodies directed against CMV immediate early nuclear protein and early nuclear protein (Clones CCH2\u0026thinsp;+\u0026thinsp;DDG9; DAKO, Glostrup, Denmark).\u003c/p\u003e \u003cp\u003eData were systematically collected from the electronic medical records. For the case patients, \u0026ldquo;time of diagnosis\u0026rdquo; was defined as the time of CMV diagnosis with pathologic confirmation; for the control subjects, the time of CMV disease in the corresponding case patient was used. Variables analyzed for both case patients and control subjects included demographic characteristics, laboratory data, CMV antigenemia at time of diagnosis, type of involved organ that was pathologically confirmed, chemotherapy regimen, high-dose corticosteroid administration (\u0026ge;\u0026thinsp;20 mg per day of prednisolone for \u0026ge;\u0026thinsp;2 weeks, equivalent or more) and transfusion within one month before diagnosis. Treatment failure, which was defined as death from CMV disease or recurrence in the same organ after treatment initiation, and all-cause mortality were investigated. We obtained ethical approval from the institutional review board of Samsung Medical Center (SMC 2022-06-099-001) and informed consent was waived as a retrospective study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eTo evaluate the differences between the two patient groups, Student\u0026rsquo;s t-test and the Mann-Whitney U-test were used to compare continuous variables, and chi-square test and Fisher\u0026rsquo;s exact test were used to compare categorical variables. We used a multivariable logistic regression model to identify risk factors for CMV disease and overall mortality. All p-values were 2-tailed, and those\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. SPSS 27.0 (IBM, Armonk, NY, USA) was used for all statistical analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 60 patients with hematologic malignancy and who were diagnosed with CMV diseases, excluding those who underwent allogeneic HSCT, were identified among hospitalized patients at Samsung Medical Center from January 2012 through July 2022. The most common underlying disease was lymphoma (n\u0026thinsp;=\u0026thinsp;49, 81.7%), and the most common site of infection was the gastrointestinal tract (n\u0026thinsp;=\u0026thinsp;48, 80%). There were no statistical differences in demographics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) other than body-mass index (BMI). At the time of CMV disease diagnosis, anemia, thrombocytopenia, and hypoalbuminemia were significantly higher in the case group than in the control. In the case group, high-dose corticosteroid administration and transfusion history within one month before diagnosis were significantly higher.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of hematologic malignancy patients with CMV organ disease and matched controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase (N\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (N\u0026thinsp;=\u0026thinsp;120)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eN (%) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median (IQR)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.25\u0026thinsp;\u0026plusmn;\u0026thinsp;13.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.05\u0026thinsp;\u0026plusmn;\u0026thinsp;15.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (48.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (61.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0883\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.30\u0026thinsp;\u0026plusmn;\u0026thinsp;3.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.40\u0026thinsp;\u0026plusmn;\u0026thinsp;3.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematologic malignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (81.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (81.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple myeloma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMV organ disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper GI tract\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (36.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower GI tract\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (43.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphadenitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory tests\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC, x10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.54 (2.74\u0026ndash;9.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.18 (4.05\u0026ndash;6.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.7163\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eANC, x10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.72 (1.92\u0026ndash;8.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.66 (2.05\u0026ndash;3.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALC, x10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.40 (0.18\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.56 (1.15\u0026ndash;2.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.3361\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin, g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.9 (7.9\u0026ndash;10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.8 (11.1\u0026ndash;14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet, x10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.0 (29.0\u0026ndash;170.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e186.0 (124.5\u0026ndash;236.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin, g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9 (2.6\u0026ndash;3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.3 (4.0\u0026ndash;4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal bilirubin, mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.60 (0.40\u0026ndash;1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.50 (0.40\u0026ndash;0.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR, mm/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.00 (4.25\u0026ndash;38.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.00 (10.00\u0026ndash;55.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.1186\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC-reactive protein, mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.80 (1.11\u0026ndash;6.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.70 (0.15\u0026ndash;3.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2829\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMV antigenemia, per 200,000 WBCs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0, 53.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy regimen within 1 month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRituximab included\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSteroid administration within 1 month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (17.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRed blood cell transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (86.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFresh frozen plasma/cryoprecipitate transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (21.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (30.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cp\u003eAbbreviations: SD, standard deviation; IQR, interquartile range; CMV, cytomegalovirus; BMI, body-mass index; GI, gastrointestinal; WBC, white blood cell; ANC, absolute neutrophil count; ALC, absolute lymphocyte count\u003c/p\u003e\u003c/p\u003e\u003cp\u003eMultivariable analysis was performed to determine risk factors for development of CMV diseases (Table 2). After fitting a conditional logistic regression model, low BMI (BMI \u0026lt;23) and hypoalbuminemia (albumin \u0026lt;3.5) significantly increased the risk of developing CMV organ disease. If there was a history of high-dose corticosteroid administration or RBC transfusion within one month, CMV disease incidence increased 5.78 times and 14.63 time, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eMultivariable analysis of risk factors for development of CMV organ disease\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.38461538461539%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"54.61538461538461%\"\u003e\n \u003cp\u003eAdjusted analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eRisk factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003eaOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eLow BMI (BMI \u0026lt;23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e13.46 (2.07\u0026ndash;87.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.006*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eSteroid within 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e5.78 (1.25\u0026ndash;26.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.024*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eRBC transfusion within 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e14.63 (2.75\u0026ndash;77.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eWBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e0.22 (0.04\u0026ndash;1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.077\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eANC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e5.15 (0.79\u0026ndash;33.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eALC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e4.47 (0.84\u0026ndash;23.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eHypoalbuminemia (albumin \u0026lt;3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e26.48 (5.93\u0026ndash;118.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: aOR, adjusted odds ratio; CI, confidence interval; BMI, body-mass index; RBC, red blood cell; ANC, absolute neutrophil count; ALC, absolute lymphocyte count\u003c/p\u003e\n\u003cp\u003eAll patients with CMV diseases, except one receiving oral valganciclovir, received IV ganciclovir for CMV treatment. The overall treatment failure rate of patients with CMV diseases was 30%, and the 30-day mortality after diagnosis of CMV disease was significantly higher in the case group than in the control. A multivariable analysis showed that development of CMV diseases was significantly associated with all-cause mortality (Table 3). Figure 1 shows the survival curve from the time of CMV diagnosis to July, 2022, for both groups. 90% of the case group and 21 patients died during the follow-up period. The mortality of patients with CMV disease was significantly higher, suggesting that the prognosis of CMV diseases in hematologic malignancy patients was poor.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eMultivariable analysis of risk factors for all-cause mortality\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.38461538461539%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"54.61538461538461%\"\u003e\n \u003cp\u003eAdjusted analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eRisk factor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003eaOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eMale sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e5.93 (1.81\u0026ndash;19.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.003*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eRBC transfusion within 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e47.24 (1.60\u0026ndash;1393.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.026*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003ePLT transfusion within 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e0.03 (0.00\u0026ndash;1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e0.74 (0.57\u0026ndash;0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.023*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e0.99 (0.99\u0026ndash;1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e0.044*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.472061657032754%\"\u003e\n \u003cp\u003eCMV disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.15028901734104%\"\u003e\n \u003cp\u003e14.41 (3.23\u0026ndash;64.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.377649325626205%\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: aOR, adjusted odds ratio; CI, confidence interval; RBC, red blood cell; PLT, platelet; Hb, hemoglobin; CMV, cytomegalovirus\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first matched case-control study to evaluate risk factors for developing CMV organ disease in hematologic malignancy patients who did not receive HSCT. We determined that low BMI, corticosteroid use, prior RBC transfusion, and hypoalbuminemia were independent risk factors for CMV diseases. Such variables have biological plausibility and did not differ significantly from previous studies results for HSCT patients [4, 5]. In previous research from our center regarding CMV colitis in immunocompetent patients, steroid administration and RBC transfusion history were also identified as risk factors [10].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn a recent study of 6,837 Korean women between the ages of 15 and 49, CMV IgG seroprevalence was 95.8% [11]. Another previous study including 710 liver transplantation recipients in Korea reported all patients to be seropositive [12], and it could be concluded, that most cases in this study are reactivations rather than primary infections, although they did not test for CMV-specific antibody.\u003c/p\u003e\n\u003cp\u003eThe strength of our study is that it expanded study subject inclusion relative to previous studies that mainly focused on HSCT to also include patients with hematologic malignancies who did not receive HSCT. It could be assumed that GI-involved disease was the most common in our study because biopsy is relatively easy to perform for the GI tract. However, stringent patient selection was made by including only pathologically confirmed patients. We also found that CMV organ disease was a predictor of poor prognosis even in hematologic malignancy patients who did not receive HSCT.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, because this study was a retrospective study, it is not possible to know the causal relationship between the revealed risk factors. Therefore, a prospective study is further needed. Second, the number of included cases was relatively small (n=60). However, we tried to overcome this disadvantage by performing a matched case-control study (1:2 ratio). Third, only pathologically confirmed cases were included for definitive diagnosis. Thus, a selection bias may have occurred due to the exclusion of patients who did not undergo biopsy. Fourth, although the CMV antigenemia test is more labor-intensive and does not have a standardization assay [14], it is more frequently used than PCR test for CMV-DNA in our institution because of cost issues. However, the antigenemia test was difficult to perform in hematologic malignancy patients who have profound neutropenia. Therefore, the usefulness of CMV antigenemia could not be evaluated in this study. Finally, it was difficult to evaluate the risk of specific drugs because the types of hematologic malignancies included in this study and the treatment medications were diverse. Previous studies found that dasatinib, which suppresses T-cell activation and proliferation, when administered to chronic myeloid leukemia patients, may be a potential risk factor for CMV reactivation, but further research is needed on other anti-cancer drugs [15, 16].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, we formally assessed the risk factors for development of CMV organ diseases in hematologic malignancy patients without HSCT, showing that high-dose corticosteroid, RBC transfusion within one month, low BMI, and hypoalbuminemia are independent risk factors. Furthermore, overall mortality was significantly higher when CMV disease occurred, and the occurrence of CMV disease was found to be a significant risk factor for mortality.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCMV: cytomegalovirus\u003c/p\u003e\n\u003cp\u003eHIV: human immunodeficiency virus\u003c/p\u003e\n\u003cp\u003eHSCT: hematopoietic stem-cell transplantation\u003c/p\u003e\n\u003cp\u003eGVHD: graft-versus-host disease\u003c/p\u003e\n\u003cp\u003eBMI: body-mass-index\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eEthics approval and consent to participate\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by\u0026nbsp;the institutional review board of Samsung Medical Center (SMC 2022-06-099-001) and informed consent was waived as a retrospective study. All experiments were performed in accordance with relevant guidelines and regulations (such as the Declaration of Helsinki).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvilability of data and materials\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting interests\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthors\u0026rsquo; con\u003c/u\u003e\u003cu\u003etributions\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jinyoung Yang, Young Ho Lee, Jaehoon Ko, Kyungmin Huh, Cheol-In Kang. The first draft of the manuscript was written by Jinyoung Yang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAcknowledements\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthor information\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eJinyoung Yang, [email protected]\u003c/p\u003e\n\u003cp\u003eYoung Ho Lee, [email protected]\u003c/p\u003e\n\u003cp\u003eJae-Hoon Ko, \u0026nbsp; [email protected]\u003c/p\u003e\n\u003cp\u003eKyungmin Huh, [email protected]\u003c/p\u003e\n\u003cp\u003eSun Young Cho, [email protected]\u003c/p\u003e\n\u003cp\u003eDoo Ryeon Chung, [email protected]\u003c/p\u003e\n\u003cp\u003eKyong Rak Pcek, [email protected]\u003c/p\u003e\n\u003cp\u003eChul Won Jung, [email protected]\u003c/p\u003e\n\u003cp\u003eCheol-In Kang, [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlonso-\u0026Aacute;lvarez S, Colado E, Moro-Garc\u0026iacute;a MA, Alonso-Arias R. Cytomegalovirus in Haematological Tumours.Front Immunol. 2021 Oct18;12:703256. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2021.703256\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2021.703256\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoeckh M, Geballe AP. Cytomegalovirus: pathogen, paradigm, and puzzle. J Clin Invest. 2011 May;121(5):1673\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1172/JCI45449\u003c/span\u003e\u003cspan address=\"10.1172/JCI45449\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePande A, Dubberke ER. Cytomegalovirus Infections of the Stem Cell Transplant Recipient and Hematologic Malignancy Patient. Infect Dis Clin North Am. 2019 Jun;33(2):485\u0026ndash;500. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.idc.2019.02.008\u003c/span\u003e\u003cspan address=\"10.1016/j.idc.2019.02.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2019 Mar 30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoeckh M, Nichols WG, Papanicolaou G, Rubin R, Wingard JR, Zaia J. Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003 Sep;9(9):543\u0026ndash;58. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1083-8791(03)00287-8\u003c/span\u003e\u003cspan address=\"10.1016/s1083-8791(03)00287-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarbara JA, Tegtmeier GE. Cytomegalovirus and blood transfusion. Blood Rev. 1987 Sep;1(3):207\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0268-960x(87)90037-3\u003c/span\u003e\u003cspan address=\"10.1016/0268-960x(87)90037-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O'Gorman P et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution.Blood. 2002 Jun15;99(12):4357\u0026ndash;63. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/blood.v99.12.4357\u003c/span\u003e\u003cspan address=\"10.1182/blood.v99.12.4357\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChae YS, Sohn SK, Kim JG, Cho YY, Moon JH, Yang DH et al. Impact of alemtuzumab as conditioning regimen component on transplantation outcomes in case of CMV-seropositive recipients and donors.Am J Hematol. 2008Aug;83(8):649\u0026ndash;53. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ajh.21215\u003c/span\u003e\u003cspan address=\"10.1002/ajh.21215\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolmberg LA, Boeckh M, Hooper H, Leisenring W, Rowley S, Heimfeld S et al. Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation.Blood. 1999 Dec15;94(12):4029\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLjungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G et al. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017 Jan 1;64(1):87\u0026ndash;91. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/cid/ciw668\u003c/span\u003e\u003cspan address=\"10.1093/cid/ciw668\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2016 Sep 28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKo JH, Peck KR, Lee WJ, Lee JY, Cho SY, Ha YE et al. Clinical presentation and risk factors for cytomegalovirus colitis in immunocompetent adult patients.Clin Infect Dis. 2015 Mar15;60(6):e20-6. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/cid/ciu969\u003c/span\u003e\u003cspan address=\"10.1093/cid/ciu969\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2014 Dec 1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi R, Lee S, Lee SG, Lee EH. Seroprevalence of CMV IgG and IgM in Korean women of childbearing age.J Clin Lab Anal. 2021 Apr;35(4):e23716. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/jcla.23716\u003c/span\u003e\u003cspan address=\"10.1002/jcla.23716\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2021 Mar 30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JM, Kim SJ, Joh JW, Kwon CH, Shin M, Kim EY et al. Early and delayed onset cytomegalovirus infection of liver transplant recipients in endemic areas. Transplant Proc. 2010 Apr;42(3):884-9. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.transproceed.2010.02.025\u003c/span\u003e\u003cspan address=\"10.1016/j.transproceed.2010.02.025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO'Brien S, Ravandi F, Riehl T, Wierda W, Huang X, Tarrand J et al. Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy.Blood. 2008 Feb15;111(4):1816\u0026ndash;9. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/blood-2007-03-080010\u003c/span\u003e\u003cspan address=\"10.1182/blood-2007-03-080010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2007 Nov 26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHong SI, Kim T, Park SY, Jung J, Lee JY, Chong YP, et al. Sensitivity of the Cytomegalovirus Antigenemia Assay to Diagnose Cytomegalovirus Retinitis. Infect Chemother. 2016 Dec;48(4):302\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3947/ic.2016.48.4.302\u003c/span\u003e\u003cspan address=\"10.3947/ic.2016.48.4.302\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2016 Nov 22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi JK, Cho SY, Choi SM, Kim GH, Lee SE, Lee S, et al. Cytomegalovirus Colitis during Dasatinib Treatment for Patients with Hematologic Malignancy: Case Series and Literature Review. Infect Chemother. 2018 Jun;50(2):153\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3947/ic.2018.50.2.153\u003c/span\u003e\u003cspan address=\"10.3947/ic.2018.50.2.153\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKreutzman A, Ladell K, Koechel C, Gostick E, Ekblom M, Stenke L et al. Expansion of highly differentiated CD8 + T-cells or NK-cells in patients treated with dasatinib is associated with cytomegalovirus reactivation.Leukemia. 2011Oct;25(10):1587\u0026ndash;97. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/leu.2011.135\u003c/span\u003e\u003cspan address=\"10.1038/leu.2011.135\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2011 Jun 7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cytomegalovirus, CMV organ disease, hematologic malignancy, hematopoietic stem-cell transplantation","lastPublishedDoi":"10.21203/rs.3.rs-2744306/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2744306/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackgrounds: This study aims to evaluate the risk factors and prognosis for CMV diseases in hematologic malignancy patients without HSCT.\u003c/p\u003e\n\u003cp\u003eMethods: We performed a case-control study (1:2) between 2012 and 2022. Adults with pathologic-confirmed CMV diseases (n=60) among hematologic malignancy patients were matched and compared to whom without CMV disease.\u003c/p\u003e\n\u003cp\u003eResults: Lymphoma was the most common underlying malignancy, and gastrointestinal tract involvement was the most common CMV disease. In the case group, high-dose steroid administration and transfusion within one month before diagnosis were higher (p\u0026lt;0.001). Steroid administration (aOR=5.78; 95% confidence interval: 1.25–26.68, p=0.024), red blood cell transfusion within one month (aOR=14.63; 2.75–77.76, p=0.002), low BMI (aOR=13.46, 2.07–87.45, p=0.006), and hypoalbuminemia (aOR=26.48, 5.93–118.17, p\u0026lt;0.001) were independent risk factors associated with CMV disease. The 30-day mortality was higher in the case group and CMV disease was significantly associated with all-cause mortality (aOR=14.41, 3.23–64.31, p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eConclusions: In hematologic malignancy patients without HSCT, risk factors for CMV organ disease included high-dose steroid administration and RBC transfusion within one month, low BMI, and hypoalbuminemia. Overall mortality was significantly higher with CMV disease, and CMV disease occurrence was a significant risk factor for mortality.\u003c/p\u003e","manuscriptTitle":"Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation: a case-control study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-04-10 17:59:59","doi":"10.21203/rs.3.rs-2744306/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6c8cb873-323c-4d1a-898f-6e5a76ef585f","owner":[],"postedDate":"April 10th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-06-06T11:14:31+00:00","versionOfRecord":[],"versionCreatedAt":"2023-04-10 17:59:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2744306","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2744306","identity":"rs-2744306","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}