The role of cerebrospinal fluid EBV DNA loads in EBV-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation

Abstract

Objective To explore the role of cerebrospinal fluid (CSF) EBV DNA loads in EBV-associated central nervous system (CNS) diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods Forty six patients who had EBV-associated diseases or unexplainable CNS manifestations from 272 patients undergoing allo-HSCT were enrolled in this prospective study.Moreover,10 patients with EBV DNA-emia but without EBV-associated diseases and 5 patients who were negative for blood EBV DNA volunteered to have their CSF monitored as controls (platelet＞50 × 109/L).The EBV DNA loads of blood and CSF were monitored regularly by quantitative real-time polymerase chain reaction.Results Fourteen patients were diagnosed as EBV associated CNS diseases,including post-transplant lymphoproliferative disorder (PTLD) in t0 cases and encephalitis/myelitis in 4 cases.Except one patient with isolated CNS-PTLD,the EBV-DNA of blood was positive in all patients with EBV associated CNS diseases.The EBV DNA loads of CSF were significantly higher than those of blood (P =0.027).The levels of blood and CSF EBV DNA were declined with control of diseases in 5 patients who were responsive to the initial treatments.However,the levels of CSF EBV DNA were increased,and those of blood EBV DNA increased or remained unchanged with the development of the disease in the 9 patients who were unresponsive to the initial treatments.In addition,we observed 2 patients that their blood EBV DNA levels were decreased and lymphadenectasis became smaller,but CNS manifestations deteriorated,and the levels of CSF EBV DNA increased after intravenous rituximab-based treatment.Their CSF EBV DNA levels were decreased and neurological symptoms alleviated after treatment with intrathecal rituximab.Conclusion EBV DNA detection in CSF might be more specific and sensitive than that in blood for diagnosis,development and therapeutic evaluation of EBV-associated CNS diseases. Key words: EB virus; Cerebrospinal fluid; Central nervous system; Hematopoietic stem cell transplantation