title: Development of multifocal leukoencephalopathy in patients undergoing allogeneic stem cell transplantation-can preemptive detection of John Cunningham virus be useful?
abstract: Therapeutic options for progressive multifocal leukoencephalopathy (PML) caused by reactivation of John Cunningham virus (JCV) are limited and inefficient in preventing neurological progression and death. The current study investigated the course of JCV reactivation resulting in PML in patients undergoing allogeneic stem cell transplantation (allo-SCT) and assessed the feasibility and potential significance of preemptive JCV detection in peripheral blood, enabling early cessation of immunosuppressive therapy and immune restoration. Two allografted patients were diagnosed with PML at 188 and 808 days post-allo-SCT. Stored DNA samples of both patients, originally obtained for quantitative cytomegalovirus PCR analysis since transplantation, were evaluated for JCV. JCV reactivation in peripheral blood was found to precede the appearance of neurological symptoms by 126 and 105 days. JCV blood levels were found to be highly correlated with the steroid dosage administered for treating graft-versus-host disease (GVHD). In one patient, the cessation of immunosuppression, including steroids, led to the disappearance of JCV in peripheral blood, with a remarkable improvement in neurological symptoms. In conclusion, the current study suggests the feasibility of early detection of JCV reactivation in blood. Immune restoration at that point may prevent PML development; however prospective studies are warranted to elucidate these issues.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, 8, Ha'Aliya Street, Haifa 31096, Israel; Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel. Electronic address: s_kamenetsky@rambam.health.gov.il.
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
authors.affiliation: Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Talya
authors.initials: T
authors.lastname: Wittmann
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, 8, Ha'Aliya Street, Haifa 31096, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Henig
authors.affiliation: Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel; Microbiology-Virology Laboratory, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Zipora
authors.initials: Z
authors.lastname: Kra-Oz
authors.affiliation: Microbiology-Virology Laboratory, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Szwarcwort Cohen
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, 8, Ha'Aliya Street, Haifa 31096, Israel; Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Tsila
authors.initials: T
authors.lastname: Zuckerman
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, 8, Ha'Aliya Street, Haifa 31096, Israel; Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Netanel A
authors.initials: NA
authors.lastname: Horowitz
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, 8, Ha'Aliya Street, Haifa 31096, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Benyamini
mesh_terms: D004279:DNA, Viral / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D007577:JC Virus / Q000302:isolation & purification*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis* / Q000821:virology; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous
chemical_list: D004279:DNA, Viral
keywords: Allogeneic stem cell transplantation; Immunosuppression; JCV; PML; Preemptive detection; Viral load