Case Report: Cytomegalovirus retinitis in an HIV-negative patient with splenic mantle cell lymphoma treated with bendamustine-rituximab

Background Cytomegalovirus (CMV) retinitis following bendamustine-containing therapy is a rare opportunistic infection with limited published evidence, and its optimal management in human immunodeficiency virus (HIV)-negative patients remains poorly defined. Case presentation A 29-year-old man with stage IV splenic mantle cell lymphoma (MCL), previously treated with R-CHOP followed by bendamustine–rituximab (BR) plus ibrutinib, developed progressive bilateral visual symptoms and abdominal pain approximately three months after completing BR therapy. Colonoscopic biopsy confirmed CMV colitis, and CMV retinitis was confirmed in the right eye, with subsequent virological confirmation of intraocular CMV involvement in the left eye. Despite initial induction therapy with intravenous ganciclovir followed by oral valganciclovir, right-eye CMV retinitis progressed, necessitating repeated intravitreal ganciclovir injections and re-induction with intravenous ganciclovir. Immunologic evaluation revealed profound cellular and humoral immune dysfunction, including severe CD4+ lymphopenia (109 cells/μL) and hypogammaglobulinemia, while HIV infection and lymphoma relapse were excluded. Intravenous immunoglobulin (IVIG) replacement therapy was initiated. Because of the prolonged ocular disease course and delayed immune reconstitution, extended oral valganciclovir maintenance and multiple intravitreal ganciclovir injections were required. Serial follow-up demonstrated gradual CD4+ T-cell recovery (109 to 352 cells/μL) and increasing circulating CD19+ B-cell proportions (4.9% to 13.7%), in parallel with sustained virological control. By June 2026, visual acuity remained preserved with no evidence of active retinitis, and both aqueous humor and blood CMV polymerase chain reaction (PCR) assays were undetectable. Given sustained retinal inactivity, virological suppression, and continued lymphoma remission, antiviral therapy was discontinued. Conclusions This case highlights that cumulative therapy-associated immune dysfunction may predispose HIV-negative patients to CMV retinitis, with BR representing an important contributing exposure. For CMV retinitis in HIV-negative patients, treatment duration should be individualized according to ophthalmic findings, virological response, and stability of the underlying hematologic disease rather than relying solely on CD4+ T-cell counts.

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Journal
Frontiers in Immunology
Published
2026-10-28
DOI
https://doi.org/10.3389/fimmu.2026.1979881
Primary Topic
Cytomegalovirus and herpesvirus research
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article
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article

Case Report: Cytomegalovirus retinitis in an HIV-negative patient with splenic mantle cell lymphoma treated with bendamustine-rituximab

Hsien-Chung Lin, Ta‐Jen Lin, Wen‐Chi Yang, Jih‐Jin Tsai et al.
1 links
Frontiers in Immunology
Cytomegalovirus and herpesvirus research
article

Case Report: Cytomegalovirus retinitis in an HIV-negative patient with splenic mantle cell lymphoma treated with bendamustine-rituximab

Hsien-Chung Lin, Ta‐Jen Lin, Wen‐Chi Yang, Jih‐Jin Tsai, Yi‐Hsien Tsai
article en

Abstract

Background Cytomegalovirus (CMV) retinitis following bendamustine-containing therapy is a rare opportunistic infection with limited published evidence, and its optimal management in human immunodeficiency virus (HIV)-negative patients remains poorly defined. Case presentation A 29-year-old man with stage IV splenic mantle cell lymphoma (MCL), previously treated with R-CHOP followed by bendamustine–rituximab (BR) plus ibrutinib, developed progressive bilateral visual symptoms and abdominal pain approximately three months after completing BR therapy. Colonoscopic biopsy confirmed CMV colitis, and CMV retinitis was confirmed in the right eye, with subsequent virological confirmation of intraocular CMV involvement in the left eye. Despite initial induction therapy with intravenous ganciclovir followed by oral valganciclovir, right-eye CMV retinitis progressed, necessitating repeated intravitreal ganciclovir injections and re-induction with intravenous ganciclovir. Immunologic evaluation revealed profound cellular and humoral immune dysfunction, including severe CD4+ lymphopenia (109 cells/μL) and hypogammaglobulinemia, while HIV infection and lymphoma relapse were excluded. Intravenous immunoglobulin (IVIG) replacement therapy was initiated. Because of the prolonged ocular disease course and delayed immune reconstitution, extended oral valganciclovir maintenance and multiple intravitreal ganciclovir injections were required. Serial follow-up demonstrated gradual CD4+ T-cell recovery (109 to 352 cells/μL) and increasing circulating CD19+ B-cell proportions (4.9% to 13.7%), in parallel with sustained virological control. By June 2026, visual acuity remained preserved with no evidence of active retinitis, and both aqueous humor and blood CMV polymerase chain reaction (PCR) assays were undetectable. Given sustained retinal inactivity, virological suppression, and continued lymphoma remission, antiviral therapy was discontinued. Conclusions This case highlights that cumulative therapy-associated immune dysfunction may predispose HIV-negative patients to CMV retinitis, with BR representing an important contributing exposure. For CMV retinitis in HIV-negative patients, treatment duration should be individualized according to ophthalmic findings, virological response, and stability of the underlying hematologic disease rather than relying solely on CD4+ T-cell counts.

Frontiers in ImmunologyVol. 17
National Sun Yat-sen University (TW), Kaohsiung Medical University (TW), Kaohsiung Medical University Chung-Ho Memorial Hospital (TW), Pingtung Hospital (TW), Pingtung Veterans General Hospital (TW), Meiho University (TW)
Good health and well-being
Openalex Percentile: Top 12%
Cytomegalovirus and herpesvirus research
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