Abstract
Cytomegalovirus meningitis/meningoencephalitis is a potentially fatal complication following hematopoietic stem cell transplantation that causes significant morbidity and mortality. In the pre-transplant setting, a few cases involving lymphoid malignancies have been reported. However, there have been no reports of patients with myeloid malignancies. A 36-year-old man with relapsed acute myeloid leukemia received high-dose cytarabine-containing salvage chemotherapies and then developed grade 4 lymphopenia for more than one month. Subsequently, the patient developed pyrexia, accompanying headache, nausea, and vomiting with no abnormal brain imaging. Despite receiving antimicrobial treatment, his febrile status and headache persisted. Given that the patient had symptoms consistent with viral meningitis with no evidence of etiology other than positive cytomegalovirus-DNA in his cerebrospinal fluid and cytomegalovirus pp65 antigenemia, cytomegalovirus meningitis was diagnosed. After commencing ganciclovir treatment, the patient’s headache and febrile status rapidly improved. Cytomegalovirus meningitis/meningoencephalitis is rare before hematopoietic stem cell transplantation, but may be useful in differential diagnoses in heavily treated acute myeloid leukemia patients with central nervous system symptoms.
Similar content being viewed by others
References
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;64:87–91.
Cinque P, Cleator GM, Weber T, Monteyne P, Sindic C, Gerna G, et al. Diagnosis and clinical management of neurological disorders caused by cytomegalovirus in AIDS patients. European Union Concerted Action on Virus Meningitis and Encephalitis. J Neurovirol. 1998;4:120–32.
Matsukawa T, Goto H, Takahashi K, Asanuma S, Yasumoto A, Takahata M, et al. A fatal case of cytomegalovirus ventriculoencephalitis in a mycosis fungoides patient who received multiple umbilical cord blood cell transplantations. Int J Hematol. 2012;95:217–22.
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 Transplant. 2010;45:979–84.
Mori T, Kato J. Cytomegalovirus infection/disease after hematopoietic stem cell transplantation. Int J Hematol. 2010;91:588–95.
Mussini C, Mongiardo N, Manicardi G, Trenti F, Alessandrì A, Paolillo F, et al. Relevance of clinical and laboratory findings in the diagnosis of cytomegalovirus encephalitis in patients with AIDS. Eur J Clin Microbiol Infect Dis. 1997;16:437–44.
Storek J, Dawson MA, Storer B, Stevens-Ayers T, Maloney DG, Marr KA, et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood. 2001;97:3380–9.
Suzumiya J, Marutsuka K, Ueda S, Uno H, Eizuru Y, Sumiyoshi A. An autopsy case of necrotizing ventriculo-encephalitis caused by cytomegalovirus in Hodgkin’s disease. Acta Pathol Jpn. 1991;41:291–8.
Nagayama M, Shinohara Y, Sekiyama S, Takahashi W, Takagi S, Yamamoto M, et al. Intravascular malignant lymphomatosis manifesting clinically as bilateral sudden hearing loss and cytomegalovirus encephalitis. Neurology. 1994;44:1518–20.
Van DJ, De Ceuninck M, Snoeck HW, Schroyens W, Berneman Z. Successful treatment of cytomegalovirus encephalitis in a patient with Hodgkin’s disease in remission. Ann Hematol. 1998;76:179–81.
Vallet S, Tempescul A, Tran A, Legrand-Quillien MC, Narbonne V, Berthou C. Cytomegalovirus-associated meningoradiculoneuritis after treatment of mantle cell lymphoma with a combination of chemotherapy and rituximab. Ann Hematol. 2005;84:545–7.
Suzuki HI, Hangaishi A, Hosoya N, Watanabe T, Kanda Y, Motokura T, et al. Herpes simplex encephalitis and subsequent cytomegalovirus encephalitis after chemoradiotherapy for central nervous system lymphoma: a case report and literature review. Int J Hematol. 2008;87:538–41.
Siakantaris MP, Argyropoulos KV, Ioannou S, Papadopoulou V, Tzeletas G, Tsonis J, et al. Cytomegalovirus meningoencephalitis after rituximab treatment for primary central nervous system lymphoma. Neurologist. 2015;19:35–7.
Visani G, Petti MC, Cenacchi A, Manfroi S, Tosi P, Spadea A, et al. MEC (mitoxantrone, etoposide and intermediate dose cytarabine): an effective induction regimen for previously untreated acute non-lymphocytic leukemia. Leuk Lymphoma. 1995;19:447–51.
Hiddemann W, Büchner T, Essink M, Koch O, Stenzinger W, van de Loo J. High-dose cytosine arabinoside and mitoxantrone: preliminary results of a pilot study with sequential application (s-HAM) indicating a high antileukemic activity in refractory acute leukemias. Onkologie. 1988;11:10–2.
Miyawaki S, Kawai Y, Takeshita A, Komatsu N, Usui N, Arai Y, et al. Phase I trial of FLAGM with high doses of cytosine arabinoside for relapsed, refractory acute myeloid leukemia: study of the Japan Adult Leukemia Study Group (JALSG). Int J Hematol. 2007;86:343–7.
Logan SA, MacMahon E. Viral meningitis. BMJ. 2008;336:36–40.
Burke DG, Leonard DG, Imperiale TF, Valdez H, Karaman B, Shick E, et al. The utility of clinical and radiographic features in the diagnosis of cytomegalovirus central nervous system disease in AIDS patients. Mol Diagn. 1999;4:37–43.
Cinque P, Vago L, Brytting M, Castagna A, Accordini A, Sundqvist VA, et al. Cytomegalovirus infection of the central nervous system in patients with AIDS: diagnosis by DNA amplification from cerebrospinal fluid. J Infect Dis. 1992;166:1408–11.
Cinque P, Vago L, Dahl H, Brytting M, Terreni MR, Fornara C, et al. Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients. AIDS. 1996;10:951–8.
Bhaskaran A, Racsa L, Gander R, Southern P, Cavuoti D, Alatoom A. Interpretation of positive molecular tests of common viruses in the cerebrospinal fluid. Diagn Microbiol Infect Dis. 2013;77:236–40.
Ersvaer E, Brenner AK, Vetås K, Reikvam H, Bruserud Ø. Effects of cytarabine on activation of human T cells—cytarabine has concentration-dependent effects that are modulated both by valproic acid and all-trans retinoic acid. BMC Pharmacol Toxicol. 2015;16:12.
Hagemeister FB. Treatment of relapsed aggressive lymphomas: regimens with and without high-dose therapy and stem cell rescue. Cancer Chemother Pharmacol. 2002;49(Suppl 1):13–20.
Dixon SB, Lane A, O’Brien MM, Burns KC, Mangino JL, Breese EH, et al. Viral surveillance using PCR during treatment of AML and ALL. Pediatr Blood Cancer. 2018. https://doi.org/10.1002/pbc.26752 (Epub 2017 Aug 9).
Goerig NL, Frey B, Korn K, Fleckenstein B, Überla K, Schmidt MA, et al. Frequent occurrence of therapeutically reversible CMV-associated encephalopathy during radiotherapy of the brain. Neuro Oncol. 2016;18:1664–72.
Zhou K, Boström M, Ek CJ, Li T, Xie C, Xu Y, et al. Radiation induces progenitor cell death, microglia activation, and blood–brain barrier damage in the juvenile rat cerebellum. Sci Rep. 2017;7:46181.
Sweet C. The pathogenicity of cytomegalovirus. FEMS Microbiol Rev. 1999;23:457–82.
Acknowledgements
The authors are grateful to the staff of the Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, for their excellent patient care.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
About this article
Cite this article
Harada, K., Sekiya, N., Ikegawa, S. et al. Cytomegalovirus meningitis in a patient with relapsed acute myeloid leukemia. Int J Hematol 109, 233–238 (2019). https://doi.org/10.1007/s12185-018-2544-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-018-2544-x