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3497 Central Nervous System Disorders (CNSD) Following Hematopoietic Stem Cell Transplantation (HSCT): A Prospective Study from the Infectious Diseases Working Party (IDWP) and the Transplant Complications Working Party (TCWP), European Society of Blood and Marrow Transplantation (EBMT)

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Viral, Adult, Clinical Practice (Health Services and Quality), Bacterial, Elderly, Epidemiology, Clinical Research, Fungal, Other Pathogens, Supportive Care, Pediatric, Diseases, Infectious Diseases, Treatment Considerations, Real-world evidence, Adverse Events, Survivorship, Study Population, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Martin Schmidt-Hieber1*, Per T. Ljungman, MD, PhD2, Patrick Gilbert3*, Nina Knelange3*, Joanna Drozd-Sokolowska4*, Grzegorz Basak5*, Hermann Einsele, MD6, Gloria Tridello3*, Nour Ben Abdeljelil, MD7*, Alexander Kulagin, MD, PhD8*, Aitana Balaguer Rosello, MD, PhD9*, Elisabetta Metafuni10*, Maura Faraci, MD11*, Jolanta Gozdzik, MD, PhD12*, Rodrigo Martino, MD13*, Anna Maria Raiola14*, Regis Peffault De Latour15*, Baris Kuskonmaz16*, Alessandra Biffi, MD, PhD17*, Krzysztof Czyzewski18*, Melissa Ann Gabriel, BMBS19, Joaquín Martínez-Lopez20*, Malgorzata Mikulska21*, Zinaida Peric22*, Dina Averbuch, MD23*, Jan Styczynski, MD, PhD24* and Rafael De La Camara, MD25

1Medical University Lausitz - Carl Thiem (MUL-CT), Cottbus, Germany
2Karolinska University Hospital, Stockholm, SWE
3EBMT Leiden Study Unit, Leiden, Netherlands
4Warszawski Uniwersytet Medyczny, Warsaw, POL
5KATEDRA I KLINIKA HEMATOLOGII, TRANSPLANTOLOGII I CHORÓB WEWNĘTRZNYCH WYDZIAŁ LEKARSKI, Warsaw, AL, POL
6Department of Internal Medicine II, University Hospital Wuerzburg, Wuerzburg, Germany
7Centre National de Greffe de Moelle Osseuse, Tunis, Tunisia
8RM Gorbacheva Research Institute, Pavlov University, Saint-Petersburg, Russian Federation
9Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
10Hematology Unit, Università Cattolica Del Sacro Cuore, Rome, ITA
11HSCT Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy
12School of Medicine Jagiellonian University, Cracow, POL
13Hematology and Hemotherapy Department, Hospital de la Sant Creu i Sant Pau. IIB-Sant Pau and José Carreras Leukemia Research Institutes. Universitat Autónoma de Barcelona, Barcelona, Spain
14IRCCS Ospedale Policlinico San Martino, Genova, Italy, Genova, Italy
15BMT unit, Hôpital Saint-Louis,, Paris, France
16Department of Pediatric Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey
17Padua University Hospital, Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova, Italy
18Pediatric hematooncology and Clinical transplantology Department of Pediatric Hematology and Oncology Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun Ul. M., Bydgoszcz, Poland
19Children's Hospital Westmead, Sydney, NSW, AUS
20Department of Hematology, Hospital Universitario 12 de Octubre, CNIO, Universidad Complutense de Madrid, Madrid, Spain
21University of Genova (Department of Health Sciences, DISSAL), Genova, Italy
22Department of Hematology, University Hospital Centre Zagreb, Zagreb, Croatia
23Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, ISR
24Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, POL
25Hospital La Zarzuela, Madrid, ESP

Introduction:

A few studies have been published on the central nervous system disorders (CNSD) after HSCT. Prospective studies including a control group are lacking.

Methods:

A prospective, observational study with infectious and non-infectious CNS disorders (iCNSD and niCNSD, respectively) after HSCT as primary objectives was conducted by the IDWP and the TCWP of EBMT. For each case patient (i.e. HSCT recipient with a CNSD), two control patients were allocated and analysed prospectively by applying the following selection criteria: not developing a CNSD until inclusion and surviving after HSCT the same time as the respective case patient until development of a CNSD (the inclusion date). Control patients were stratified by age (children vs adults), centre and HSCT type (allogeneic vs. autologous).

Results:

A total of 183 patients (61 patients with a CNSD, 122 controls) from 15 centres (8 countries) were included in this study between January 2021 and April 2024. Hereby, 57 patients with a CNSD (93%) underwent allogeneic and 4 patients (7%) autologous HSCT. Nineteen (31%) case patients were children (<18 years), and 42 (69%) adults (≥ 18 years).

Twenty-two patients (36%) had a proven/probable iCNSD, 28 patients (46%) had a proven/probable niCNSD and 11 patients (18%) had a possible infectious or non-infectious or unclassified CNSD. Forty-eight patients (79%) had an acute onset of the CNSD while onset was non-acute in 13 patients (21%). Human herpes virus 6 iCNSD was the most frequent proven/probable CNS infection (n=7) while infections by Toxoplasma spp. (n=5), Aspergillus spp. (n=3), bacteria (n=2), adenovirus (n=1) or different pathogens/unspecified infections (n=4) occurred less frequently. In patients with proven/probable niCNSD drug-induced changes were dominant (n=12) but vascular pathologies (bleeding, strokes etc., n=6) occurred also besides other (n=6, e.g. metabolic encephalopathy, posterior reversible encephalopathy syndrome or CNS relapse of the underlying disease) or unspecified causes (n=4). The median interval from HSCT to the CNSD onset was 31 days (range -1-153 days) for patients with proven/probable iCNSD (n=22) and 27 days (range -5-363 days) for patients with proven/probable niCNSD (n=28, p>0.05).

Magnetic resonance imaging (MRI) was done in 45/61 patients (74%). Abnormalities associated with the CNSD were described in 15/20 patients (75%) with proven/probable iCNSD and 12/19 (63%) of patients with proven/probable niCNSD (p>0.05).

A grade 3/4 eastern cooperative oncology group status at inclusion was more frequently present in CNSD (34/60 evaluable patients, 57%) than control patients (12/122 patients, 10%, p<0.001). Other variables such as median age, sex matching, HLA matching, disease status (71% complete remission in total), conditioning type, T cell depletion and stem cell source were comparable between cases and controls. Distribution of comorbidities was also largely comparable between both groups albeit a pre-existing CNS disease prior to HSCT was more frequent in the CNSD than in the control group (20% vs. 9%, p>0.05). Patients with a CNSD at inclusion were more frequently on ward (53/60 patients, 88%) than controls (72/122 patients, 59%, p<0.001). Among controls - none of them having a CNSD between HSCT and study inclusion - , 2/111 patients (1.8%, 95%-confidence interval (CI) 0.2-6.4%) developed a CNSD at day +100 after study inclusion and 9/117 patients (7.7%, 95%-CI 3.6-14.1%) at last follow-up.

Overall survival was lower (p<0.001) in patients with a CNSD - 85% (95%-CI 76-94%) at one month and 49% (95%-CI 35-63%) at 24 months - compared to controls - 99% (95%-CI 98-100%) and 82% (95%-CI 74-89%), respectively. Causes of death among cases were the CNSD (n=14/29, 48%), HSCT-related causes other than the CNSD (n=5, 17%) relapse/progression (n=3, 10%) or other reasons (n=7, 24%). Relapse/progression was the most frequent death cause among controls (n=13/18, 72%, p<0.001). At last follow-up, 14/22 patients (64%) with a proven/probable iCNSD had died, compared to 11/28 patients (39%) with a proven/probable niCNSD (p>0.05).

Conclusions:

CNSD represent a significant complication after HSCT. Hereby, non-infectious causes prevail over CNS infections. A pre-existing CNS disease prior to HSCT might be a risk factor for a CNS complication after HSCT. Patients with a CNSD after HSCT have a reduced overall survival with the CNSD itself being the main cause of death.

Disclosures: Schmidt-Hieber: MSD: Speakers Bureau; Amgen: Speakers Bureau; Sanofi-Aventis: Speakers Bureau; Stem Line: Honoraria; MICE: Honoraria; NewConceptOncology: Honoraria; Shionogi: Speakers Bureau; BMS: Speakers Bureau. Einsele: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria; Celgene/Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Peffault De Latour: pfizer: Consultancy, Honoraria, Research Funding; soby: Consultancy, Honoraria, Research Funding; novartis: Consultancy, Honoraria, Research Funding; alexion: Consultancy, Honoraria, Research Funding. Biffi: Eusa Pharma: Consultancy; Astellas: Speakers Bureau; Bluebird: Speakers Bureau; Medac Pharma: Consultancy, Speakers Bureau; Iqone (Clinigen): Consultancy; Gilead: Consultancy; Novartis: Consultancy; Amgen: Consultancy, Speakers Bureau; Bayer: Consultancy; Takeda: Consultancy. Czyzewski: AstraZeneca: Honoraria; MSD: Honoraria; Gilead: Honoraria; Theracos: Honoraria. Martínez-Lopez: BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Incity: Research Funding. Averbuch: MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Styczynski: Roche: Other: Travel Grant; Medac: Other: Travel Grant; Sanofi: Honoraria, Speakers Bureau; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Gilead: Honoraria, Other: travel grant, Speakers Bureau; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Speakers Bureau; AbbVie: Other: Travel Grant; Chiesi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. De La Camara: MSD: Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH