gms | German Medical Science

Cytomegalovirus (CMV) disease of the central nervous system (CNS) post haematopoietic stem cell transplant (HSCT) is an uncommon occurrence. The CNS is well-known as a sanctuary site; the treatment of disease with agents without adequate CNS penetration may, in theory, lead to CNS disease. We describe two post-HSCT patients for whom this particular phenomenon occurred. Patient 1 is a 50 year old male who had a second allogeneic HSCT following relapse of underlying acute myeloid leukaemia. He received CMV negative (D-/R+) matched unrelated donor with a non-myeloablative conditioning regimen consisting of fludarabine, busulphan and anti-thymocyte globulin (ATG). He developed acute graft versus host disease (GVHD) and CMV esophagitis on day 35 post-transplant. Although this responded to both ganciclovir and foscarnet, his subsequent clinical course was characterized by recurrent episodes of antigenemia even while on valganciclovir secondary prophylaxis. Resistance to ganciclovir and foscarnet was documented. He presented with progressive demyelinating polyradiculopathy at 11 months post-transplant and CNS CMV disease was confirmed by cerebrospinal fluid (CSF) assessment. Artesunate was employed in addition to ganciclovir and foscarnet combination therapy which reduced the degree of antigenemia but had minimal effect on CNS disease. Patient 2 is a 40 year old male with underlying severe aplastic anemia who underwent matched sibling allogeneic HSCT. CMV serostatus was D+/R+. Fludarabine, cyclophosphamide with total body irradiation were used as the conditioning regimen. His post-transplant clinical course was complicated by recurrent CMV infections with documented resistance to ganciclovir and foscarnet on genotypic resistance testing. He required multiple courses of systemic anti-CMV therapy including CMV specific immunoglobulin (CMVIg), artesunate and maribavir. In addition, CMV-specific cytotoxic T lymphocyte (CTL) infusion was attempted at 3.5 months post-transplant but there was failure of reconstitution of CMV-specific immunity. Five months post-transplant, magnetic resonance imaging (MRI) of the brain demonstrated multifocal enhancing intracranial and leptomeningeal lesions with mass effect and hydrocephalus. CMV quantitative polymerase chain reaction (PCR) assay of the CSF confirmed CMV CNS disease. These two cases demonstrate the phenomenon of compartmentalization of CMV in the CNS, possibly related to the use of agents with poor CNS penetration.