Central nervous system disorders following haematopoietic stem cell transplantation: a prospective case-control observational study from the Infectious Diseases Working Party and the Transplant Complications Working Party of EBMT.
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Schmidt-Hieber Martin, Ljungman Per, Gilbert Patrick, Knelange Nina, Drozd-Sokolowska Joanna, Basak Grzegorz, Einsele Hermann, Tridello Gloria, Abdeljelil Nour B, Kulagin Alexander, Balaguer-Rosello Aitana, Metafuni Elisabetta, Faraci Maura, Gozdzik Jolanta, Martino Rodrigo, Raiola Anna M, Xhaard Alienor, Kuskonmaz Baris, Biffi Alessandra, Czyzewski Krzysztof, Gabriel Melissa A, Martínez-Lopez Joaquin, Zaidman Irina, Schlegel Paul G, Gruhn Bernd, Krivan Gergely, Vicent Marta Gonzalez, Mikulska Malgorzata, Peric Zinaida, Averbuch Dina, Styczynski Jan, Penack Olaf, Camara Rafael de la
Аннотация
METHODS: Patients were eligible for the CNSD group if they underwent HSCT between January 2021 and December 2022 at 20 centres in 11 countries and developed either an iCNSD or a niCNSD at any time after the start of conditioning prior to HSCT, up to the study termination (June 2023). Data were collected by local investigators and sent to the EBMT Leiden Study Unit, Leiden, Netherlands. For each case, two controls surviving the same period after HSCT without CNSD as the respective case were selected. Primary endpoints of this study were (1) percentage of iCNSD and niCNSD, including different causes, (2) characteristics of CNSD (e.g., percentage of patients with an abnormal brain imaging pattern), and (3) the course (e.g., mortality and overall survival [OS] = at different time points). This study is registered at ClinicalTrials.gov (NCT04737785).
FINDINGS: 237 patients (84 cases and 153 controls) were included, of whom 98 (41%) were female and 139 (59%) were male. The frequency of CNSD after HSCT was estimated at 2.9% (84 of 2910 transplanted patients, 95% CI 2.3-3.6%). Among cases, 21 (25%) had a proven/probable iCNSD, 47 (56%) had a proven/probable niCNSD, and 16 (19%) had a possible or unclassified CNSD. Human herpes virus-6 (meningo-)encephalitis was the most frequent proven/probable iCNSD (n = 9, 43%). In patients with proven/probable niCNSD, vascular pathologies were dominant (n = 15, 32%). In a multivariable Cox regression analysis, CNSD at the inclusion time point (HR 2.96, 95% CI 1.13-7.74, p = 0.027) remained the only significant predictor of inferior OS. Causes of death in the CNSD group were the CNSD (n = 15/36, 42%, eight with proven/probable iCNSD, five with proven/probable niCNSD and two with possible/unspecified CNSD), other HSCT-related causes (n = 7, 19%), relapse/progression (n = 5, 14%), or other (including multifactorial reasons, n = 9, 25%). Relapse/progression was the most frequent cause of death among controls (n = 17/25, 68%).
INTERPRETATION: CNSD represent a serious complication after HSCT with an estimated 2.9% frequency and non-infectious causes prevailing over CNS infections. Patients with a CNSD after HSCT have a reduced OS, with the CNSD itself being the main cause of death.
FUNDING: None.