[en] Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD occurred before or after day 100 following allogeneic hematopoietic stem cell transplantation. Median time between hematopoietic stem cell transplantation and pCNS-GvHD onset was 149 days (IQ25-75 48-321), and pCNS-GvHD onset occurred before day 100 following transplantation in 44% of patients. The most frequent findings at presentation were cognitive impairment (41%), paresis (21%), altered consciousness (20%), sensory impairment (18%), and headache (15%). Clinical presentation did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Brain MRI found abnormalities compatible with the clinical picture in 57% of patients, while CT detected abnormalities in only 7%. Seven patients had documented spinal cord MRI abnormalities, all of them with pCNS-GvHD occurring after day 100 following transplantation. In the cerebrospinal fluid, white blood cell count was increased in 56% of the population (median 18 cells/μL). Histopathological analyses were performed on 12 specimens and were suggestive of pCNS-GvHD in 10. All compatible specimens showed parenchymal and perivascular infiltration by CD3+ and CD163+ cells. Immunosuppressive therapy was prescribed in 97% of patients, achieving complete clinical response in 27%, partial improvement in 47% and stable disease in 6%. Response to immunosuppressive therapy did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Clinical relapse was observed in 31% of patients who initially responded to treatment. One-year overall survival following pCNS-GvHD onset was 41%. Onset before day 100 following hematopoietic stem cell transplantation (HR [95%CI]: 2.1 [1.0-4.5]; P=0.041) and altered consciousness at initial presentation (HR [95%CI]: 3.0 [1.3-6.7]; P=0.0077) were associated with a reduced one-year overall survival probability. Among surviving patients, 61% had neurological sequelae. This study supports that immune-mediated CNS manifestations may occur following allo-HSCT. These can be associated with both acute and chronic GvHD and carry a grim prognosis. The clinical presentation as well as the radiological and biological findings appear variable.
Lambert, Nicolas ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Forte, Florence ; Centre Hospitalier Universitaire de Liège - CHU > > Service de neurologie
El Moussaoui, Majdouline ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Maladies infectieuses et médecine interne générale
Monseur, Justine ; Université de Liège - ULiège > Département des sciences de la santé publique > Biostatistique
Raus, Nicole; Department of Hematology Marcel-Bérard secteur 1G, Centre hospitalier Lyon sud, 69310 Pierre-Bénite, France
Polushin, Alexey; Department of Chemotherapy and Stem Cell Transplantation for Cancer and Autoimmune Diseases, First Pavlov State Medical University of St. Peterburg, 197022 Saint Petersburg, Russia
Michonneau, David; Hematology and transplantation unit, Saint Louis hospital, Université Paris Cité, 75010 Paris, France
Shultz, Carl; Division of Hematology, Mayo Clinic, 55905 Rochester, Minnesota, USA
Hogan, William J; Division of Hematology, Mayo Clinic, 55905 Rochester, Minnesota, USA
Balaguer-Roselló, Aitana; Hospital Universitari i Politècnic la Fe, 46026 Valencia, Spain
Gil-Perotìn, Sara ; Hospital Universitari i Politècnic la Fe, 46026 Valencia, Spain
Brijs, Jan; Department of Hematology, University Hospitals Leuven, 3000 Leuven, Belgium
Chauvet, Paul; CHU de Lille, Maladies du Sang, Université de Lille, 59000 Lille, France
Gavriilaki, Maria; First Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Carre, Martin; Department of Hematology, Hôpital Michallon, 38043 Grenoble, France
Dulamea, Adriana Octaviana; Department of Neurology, University of Medicine and Pharmacy "Carol Davila", Fundeni Clinical Institute, Bucharest 022328, Romania
Chalandon, Yves ; Division of Hematology, University Hospital of Geneva (HUG) and faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland
Salmenniemi, Urpu; HUCH Comprehensive Cancer Center, Stem Cell Transplantation Unit - Helsinki, 00029 Helsinki, Finland
Duminuco, Andrea; Department of Hematology with BMT, A.O.U. Policlinico "G.Rodolico-San Marco", 95123 Catania, Italy
Ram, Ron; BMT Unit, Tel Aviv Sourasky Medical Center and Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel
García-Cadenas, Irene; Department of Hematology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain
Porto, Gaetana; Department of Hemato-Oncology and Radiotherapy, Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", 89100 Reggio Calabria, Italy
Nguyen, Stéphanie; Department of Hematology, Pitie-Salpetriere Hospital, 75013 Paris, France
Smallbone, Portia; Department of Hematology, Fiona Stanley Hospital, 6150 Perth, Western Australia
González-Vicent, Marta; BMT Unit, Hospital Niño Jesus, 28009 Madrid, Spain
Santoro, Jonathan D ; Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 90027 Los Angeles, California, USA
Willems, Evelyne ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique
Baron, Frédéric ; Université de Liège - ULiège > Département des sciences cliniques
Servais, Sophie ; Université de Liège - ULiège > Département des sciences cliniques
Beguin, Yves ; Université de Liège - ULiège > Département des sciences cliniques
Maquet, Pierre ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie
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