CNS manifestations in acute and chronic graft-versus-host disease
Por:
Lambert, N, Forte, F, El Moussaoui, M, Monseur, J, Raus, N, Polushin, A, Michonneau, D, Shultz, C, Hogan, WJ, Balaguer-Roselló, A, Gil-Perotín, S, Brijs, J, Chauvet, P, Gavriilaki, M, Carre, M, Dulamea, AO, Chalandon, Y, Salmenniemi, U, Duminuco, A, Ram, R, García-Cadenas, I, Porto, G, Nguyen, S, Smallbone, P, González-Vicent, M, Santoro, JD, Willems, E, Baron, F, Servais, S, Beguin, Y, Maquet, P
Publicada:
1 abr 2025
Ahead of Print:
1 feb 2025
Resumen:
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 multicentre retrospective study, we analysed 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 onset occurred before or after Day 100 following allogeneic haematopoietic stem cell transplantation (allo-HSCT).The median time between allo-HSCT and pCNS-GvHD onset was 149 days (interquartile range25-75 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 CSF, the white blood cell count was increased in 56% of the population (median 18 cells/mu l). 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 differ significantly 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 haematopoietic stem cell transplantation [hazard ratio with 95% confidence interval: 2.1 (1.0-4.5); P = 0.041] and altered consciousness at initial presentation [3.0 (1.3-6.7); P = 0.0077] were associated with a reduced 1-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.
In a retrospective international multicentre study, Lambert et al. describe the clinical, biological, radiological, and histopathological characteristics, as well as the course and treatment response, of a large cohort of patients with CNS involvement in graft-versus-host disease.
Filiaciones:
Lambert, N:
Univ Hosp Liege, Dept Neurol, B-4000 Liege, Belgium
Forte, F:
Univ Hosp Liege, Dept Neurol, B-4000 Liege, Belgium
El Moussaoui, M:
Univ Hosp Liege, Dept Infect Dis & Gen Internal Med, B-4000 Liege, Belgium
Monseur, J:
Univ Liege, Biostat & Res Methods Ctr B STAT, Dept Publ Hlth, B-4000 Liege, Belgium
Raus, N:
Ctr Hosp Lyon sud, Dept Hematol, Marcel Berard Sect 1G, F-69310 Pierre Benite, France
Polushin, A:
First Pavlov State Med Univ St Peterburg, Dept Chemotherapy & Stem Cell Transplantat Canc &, St Petersburg 197022, Russia
Michonneau, D:
Univ Paris Cite, St Louis Hosp, Hematol & Transplantat Unit, F-75010 Paris, France
Shultz, C:
Mayo Clin, Div Hematol, Rochester, MN 55905 USA
Hogan, WJ:
Mayo Clin, Div Hematol, Rochester, MN 55905 USA
Balaguer-Roselló, A:
Hosp Univ & Politecn La Fe, Dept Hematol, Valencia 46026, Spain
Gil-Perotín, S:
Hosp Univ & Politecn La Fe, Dept Neurol, Valencia 46026, Spain
Brijs, J:
Univ Hosp Leuven, Dept Hematol, B-3000 Leuven, Belgium
Chauvet, P:
Univ Lille, CHU Lille, F-59000 Lille, France
Gavriilaki, M:
Aristotle Univ Thessaloniki, AHEPA Univ Hosp, Dept Neurol 1, Thessaloniki 54636, Greece
Carre, M:
Hop Michallon, Dept Hematol, F-38043 Grenoble, France
Dulamea, AO:
Univ Med & Pharm Carol Davila, Fundeni Clin Inst, Dept Neurol, Bucharest 022328, Romania
Chalandon, Y:
Univ Geneva, Univ Hosp Geneva HUG, Div Hematol, CH-1205 Geneva, Switzerland
Univ Geneva, Fac Med, CH-1205 Geneva, Switzerland
Salmenniemi, U:
HUCH Comprehens Canc Ctr, Stem Cell Transplantat Unit, Helsinki 00029, Finland
Duminuco, A:
AOU Policlin G Rodol San Marco, Dept Hematol BMT, I-95123 Catania, Italy
Ram, R:
Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, BMT Unit, IL-6423906 Tel Aviv, Israel
Tel Aviv Univ, Fac Med, IL-6423906 Tel Aviv, Israel
García-Cadenas, I:
Hosp Santa Creu & Sant Pau, Pharm Dept, Barcelona 08025, Spain
Porto, G:
Grande Osped Metropolitano ?Bianchi Melacrino More, Dept Hemato Oncol & Radiotherapy, Stem Cell Transplantat & Cellular Therapies Unit C, I-89100 Reggio Di Calabria, Italy
Nguyen, S:
Hop La Pitie Salpetriere, Dept Hematol, F-75013 Paris, France
Smallbone, P:
Fiona Stanley Hosp, Dept Hematol, Perth, WA 6150, Australia
González-Vicent, M:
Hosp Nino Jesus, BMT Unit, Madrid 28009, Spain
Santoro, JD:
Childrens Hosp Los Angeles, Dept Pediat, Div Neurol, Los Angeles, CA 90027 USA
Willems, E:
Univ Hosp Liege, Dept Hematol, B-4000 Liege, Belgium
Baron, F:
Univ Hosp Liege, Dept Hematol, B-4000 Liege, Belgium
Servais, S:
Univ Hosp Liege, Dept Hematol, B-4000 Liege, Belgium
Beguin, Y:
Univ Hosp Liege, Dept Hematol, B-4000 Liege, Belgium
Maquet, P:
Univ Hosp Liege, Dept Neurol, B-4000 Liege, Belgium
Green Submitted, hybrid
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