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Peer-reviewedCC BY 4.0Frontiers in Immunology

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

  • Yi-Hsien Tsai1
  • Hsien-Chung Lin2
  • Wen-Chi Yang3,4,5
  • Ta-Jen Lin1
  • Jih-Jin Tsai6,7,8
8 affiliations
  1. 1School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University
  2. 2Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University
  3. 3Division of Hematology and Medical Oncology, Department of Internal Medicine, Pingtung Veterans General Hospital
  4. 4Department of Nursing, Meiho University
  5. 5School of Medicine, National Sun Yat-sen University
  6. 6School of Medicine, College of Medicine, Kaohsiung Medical University
  7. 7Tropical Medicine Center, Kaohsiung Medical University Hospital
  8. 8Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital
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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.

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Cite

BibTeXRIS
BibTeX
@article{tsai2026case,
  title = {{Case Report: Cytomegalovirus retinitis in an HIV-negative patient with splenic mantle cell lymphoma treated with bendamustine-rituximab}},
  author = {Yi-Hsien Tsai and Hsien-Chung Lin and Wen-Chi Yang and Ta-Jen Lin and Jih-Jin Tsai},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1979881},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1979881/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Case Report: Cytomegalovirus retinitis in an HIV-negative patient with splenic mantle cell lymphoma treated with bendamustine-rituximab
AU  - Yi-Hsien Tsai
AU  - Hsien-Chung Lin
AU  - Wen-Chi Yang
AU  - Ta-Jen Lin
AU  - Jih-Jin Tsai
PY  - 2026
DA  - 2026/10/28
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1979881
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1979881/full
AB  - 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.
SN  - 1664-3224
ER  -