International Journal of Hematology

, Volume 95, Issue 2, pp 217–222 | Cite as

A fatal case of cytomegalovirus ventriculoencephalitis in a mycosis fungoides patient who received multiple umbilical cord blood cell transplantations

  • Toshihiro MatsukawaEmail author
  • Hideki Goto
  • Kenta Takahashi
  • Shinsuke Asanuma
  • Atsushi Yasumoto
  • Mutsumi Takahata
  • Akio Shigematsu
  • Tomoyuki Endo
  • Junji Tanaka
  • Satoshi Hashino
  • Shinya Tanaka
  • Masahiro Imamura
Case Report


Cytomegalovirus (CMV) infection is latent in the majority of adult humans. The reactivation of CMV causes pneumonia and gastrointestinal disease in severely immunosuppressed patients, who consequently suffer very high mortality due to CMV central nervous system disease. We report here a case involving a 28-year-old female patient with mycosis fungoides who underwent umbilical cord blood transplantation three times and developed CMV ventriculoencephalitis. The patient’s CMV viremia was successfully preempted with ganciclovir (GCV) as indicated by undetectable CMV antigenemia; despite this successful treatment, the patient developed CMV ventriculoencephalitis. Foscarnet (FCV) therapy led to a temporary recovery, after which CMV ventriculoencephalitis recurred, and the patient died after receiving combination GCV and FCV therapy. Autopsy samples revealed CMV ventriculoencephalitis, as indicated by numerous inclusion-bearing cells (Owl’s eye). It is likely that this patient harbored a GCV-resistant CMV strain; however, it was not possible to obtain nucleic acids suitable for use in assessing this possibility.


Cytomegalovirus ventriculoencephalitis Ganciclovir resistance Umbilical cord blood transplantation Mycosis fungoides Inclusion-bearing cells 


Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Kim YH, Liu HL, Mraz-Gernhard S, Varghese A, Hoppe RT. Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome: clinical prognostic factors and risk for disease progression. Arch Dermatol. 2003;139:857–66.PubMedCrossRefGoogle Scholar
  2. 2.
    Arulogun SO, Prince HM, Nq J, Lade S, Ryan GF, Blewitt O, et al. Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation. Blood. 2008;112:3082–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Bolovan-Fritts CA, Mocarski ES, Wiedeman JA. Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood. 1999;93:394–8.PubMedGoogle Scholar
  4. 4.
    Kondo K, Kaneshima H, Mocarski ES. Human cytomegalovirus latent infection of granulocyte-macrophage progenitors. Proc Natl Acad Sci USA. 1994;91:11879–83.PubMedCrossRefGoogle Scholar
  5. 5.
    Seo SK, Regan A, Cihlar T, Lin DC, Boulad F, George D, et al. Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance. Clin Infect Dis. 2001;33:e105–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Julin JE, van Burik JH, Krivit W, Webb C, Holman DJ, Clark HB, et al. Ganciclovir-resistant cytomegalovirus encephalitis in a bone marrow transplant recipient. Transpl Infect Dis. 2002;4:201–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Hamprecht K, Eckle T, Prix L, Faul C, Einsele H, Jahn G. Ganciclovir-resistant cytomegalovirus disease after allogeneic stem cell transplantation: pitfalls of phenotypic diagnosis by in vitro selection of an UL97 mutant strain. J Infect Dis. 2003;187:139–43.PubMedCrossRefGoogle Scholar
  8. 8.
    Wolf DG, Lurain NS, Zuckerman T, Hoffman R, Satinger J, Honigman A, et al. Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients. Blood. 2003;101:463–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Zeiser R, Grullich C, Bertz H, Pantazis G, Hufert FT, Bley TA, et al. Late cytomegalovirus polyradiculopathy following haploidentical CD34+ selected hematopoietic stem cell transplantation. Bone Marrow Transpl. 2004;33:243–5.CrossRefGoogle Scholar
  10. 10.
    Battiwalla M, Paplham P, Almyroudis NG, McCarthy A, Abdelhalim A, Elefante A, et al. Leflunomide failure to control recurrent cytomegalovirus infection in the setting of renal failure after allogeneic stem cell transplantation. Transpl Infect Dis. 2007;9:28–32.PubMedCrossRefGoogle Scholar
  11. 11.
    Miller GG, Boivin G, Dummer JS, McConnell T, Becher MW, Kassim A. Cytomegalovirus ventriculoencephalitis in a peripheral blood stem cell transplant recipient. Clin Infect Dis. 2006;42:e26–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Hubacek P, Keslova P, Formankova R, Pochop P, Cinek O, Zajac M, et al. Cytomegalovirus encephalitis/retinitis in allogeneic haematopoietic stem cell transplant recipient treated successfully with combination of cidofovir and foscarnet. Pediatr Transpl. 2009;13:919–22.CrossRefGoogle Scholar
  13. 13.
    Reddy SM, Winston DJ, Territo MC, Schiller GJ. CMV central nervous system disease in stem-cell transplant recipients: an increasing complication of drug-resistant CMV infection and protracted immunodeficiency. Bone Marrow Transpl. 2010;45:979–84.CrossRefGoogle Scholar
  14. 14.
    Sarva H, Graber J, Remanan R, Rosenblum M, Omuro A. CMV encephalitis in BMT patients. Bone Marrow Transpl 2011. doi: 10.1038/bmt.2011.80.
  15. 15.
    Akpek G, Mikulski M, Kleinberg M, Badros A, Yanovich S, Rapoport AP. Cellular therapy with sequential unmanipulated donor lymphocyte infusions in drug-resistant cytomegalovirus (CMV) encephalitis. Blood. 2011;117:5772–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Lee S, Kim SH, Choi SM, Lee DG, Kim SY, Lee JW, et al. Cytomegalovirus ventriculoencephalitis after unrelated double cord blood stem cell transplantation with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia. J Kor Med Sci. 2010;25:630–3.CrossRefGoogle Scholar
  17. 17.
    Ando T, Mitani N, Yamashita K, Takahashi T, Ohama E, Miyata H, et al. Cytomegalovirus ventriculoencephalitis in a reduced-intensity conditioning cord blood transplant recipient. Transpl Infect Dis. 2010;12:441–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Maschke M, Kastrup O, Diener HC. CNS manifestations of cytomegalovirus infections: diagnosis and treatment. CNS Drugs. 2002;16:303–15.PubMedCrossRefGoogle Scholar
  19. 19.
    Seok JH, Ahn K, Park HJ. Diffusion MRI findings of cytomegalovirus-associated ventriculitis: a case report. Br J Radiol. 2011;84:e179–81.PubMedCrossRefGoogle Scholar
  20. 20.
    Post MJD, Hensley GT, Moskowitz LB, Fischl M. Cytomegalic inclusion virus encephalitis in patients with AIDS: CT, clinical, and pathologic correlation. Am J Neuroradiol. 1986;7:275–9.Google Scholar
  21. 21.
    Griffiths P. Cytomegalovirus infection of the central nervous system. Herpes. 2004;11(Suppl2):95A–104A.PubMedGoogle Scholar
  22. 22.
    Bylsma SS, Achim CL, Wiley CA, Gonzalez C, Kuppermann BD, Berry C, et al. The predictive value of cytomegalovirus retinitis for cytomegalovirus encephalitis in acquired immunodeficiency syndrome. Arch Ophthalmol. 1995;113:89–95.PubMedCrossRefGoogle Scholar
  23. 23.
    Thurnher MM, Thurnher SA, Schindler E. CNS involvement in AIDS: spectrum of CT and MR findings. Eur Radiol. 1997;7:1092–7.CrossRefGoogle Scholar
  24. 24.
    Rubin DI. NeuroImages. “Owl’s eye” of CMV ventriculitis. Neurology. 2000;54:2217.PubMedGoogle Scholar
  25. 25.
    Fletcher C, Sawchuk R, Chinnock B, de Miranda P, Balfour HH Jr. Human pharmacokinetics of the antiviral drug DHPG. Clin Pharmacol Ther. 1986;40:281–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Raffi F, Taburet AM, Ghaleh B, Huart A, Singlas E. Penetration of foscarnet into cerebrospinal fluid of AIDS patients. Antimicrob Agents Chemother. 1993;37:1777–80.PubMedGoogle Scholar
  27. 27.
    Wolf DG, Lee DJ, Spector SA. Detection of human cytomegalovirus mutations associated with ganciclovir resistance in cerebrospinal fluid of AIDS patients with central nervous system disease. Antimicrob Agents Chemother. 1995;39:2552–4.PubMedGoogle Scholar
  28. 28.
    Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev. 2010;23:689–712.PubMedCrossRefGoogle Scholar
  29. 29.
    Reusser P, Riddell SR, Meyers JD, Greenberg PD. Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood. 1991;78:1373–80.PubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2012

Authors and Affiliations

  • Toshihiro Matsukawa
    • 1
    Email author
  • Hideki Goto
    • 1
  • Kenta Takahashi
    • 2
  • Shinsuke Asanuma
    • 1
  • Atsushi Yasumoto
    • 1
  • Mutsumi Takahata
    • 1
  • Akio Shigematsu
    • 1
  • Tomoyuki Endo
    • 1
  • Junji Tanaka
    • 1
  • Satoshi Hashino
    • 1
  • Shinya Tanaka
    • 2
  • Masahiro Imamura
    • 1
  1. 1.Stem Cell Transplantation CenterHokkaido University HospitalSapporoJapan
  2. 2.Department of Pathology, Laboratory of Cancer ResearchHokkaido University Graduate School of MedicineSapporoJapan

Personalised recommendations