Transplant Cell Ther. 2025 Dec 31:S2666-6367(25)02655-7. doi: 10.1016/j.jtct.2025.12.994. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVES: Atypical manifestations of chronic graft-versus-host disease (cGVHD) can affect both the central and peripheral nervous system, presenting with diverse clinical and para-clinical features. These manifestations are often difficult to distinguish from other neurological conditions, particularly those resulting from drug toxicity and opportunistic infections. To date, only rough diagnostic criteria for these rare manifestations have been proposed. The objective of this study was to contribute additional data to the existing literature and to develop more specific diagnostic criteria for cGVHD affecting the central nervous system (CNS).
METHODS: Based on the 2020 NIH Report on atypical cGVHD and an interdisciplinary approach, we propose three distinct forms of CNS-cGVHD: vasculitis-like, demyelinating, and meningoencephalitis. A scoring system was developed to categorize the likelihood of CNS-cGVHD as unlikely, possible, or probable. The score was applied in a retrospective review of all patients who underwent allo-HSCT at the University Hospital of Regensburg between 2007 and 2022, focusing on those with suspected cGVHD of the CNS by analyzing the neurological symptoms, diagnostic findings, and clinical course of all patients.
RESULTS: Out of 770 patients who underwent allo-HSCT, 19 (2.5%) were identified with possible (n=6) or probable (n=13) cGVHD affecting the CNS (12 patients with meningoencephalitis, four patients with vasculitis-like and one patient with demyelinating cGVHD; two patients presented with 'mixed phenotype' showing symptoms of two entities). 1st-line treatment comprised corticosteroids for most cases (18/19), with eight patients receiving at least two agents concomitantly as part of the initial therapeutic regimen. A clinical response to 1st-line therapy was observed in 12 patients. In median, 2 therapy lines were administered for treatment of CNS-cGVHD, with 14 patients showing a response to immunosuppressive treatment (IST), while five patients did not respond to IST. The six-month and one-year overall survival following CNS-cGVHD onset was both 78%. Cause of death was at least partly attributed to CNS-cGVHD in four patients, extra-neurological cGVHD in two patients, cardiovascular disease in one patient and cerebral hemorrhage in another patient, while one patient succumbed to relapse of acute myeloid leukemia. Approximately half of the patients (8/19) suffered from long-lasting (> 6 months) neurological sequelae.
DISCUSSION: Diagnosing atypical cGVHD remains a significant challenge and necessitates interdisciplinary discussions between neurologists and hematologists on a case-by-case basis. We propose new diagnostic criteria aimed at standardizing the diagnostic process for CNS manifestations of cGVHD.
CONCLUSION: With an incidence of 2.5%, CNS-cGVHD is a rare but serious complication after allo-HSCT, associated with long-term neurologic sequelae; early diagnosis and early IST may improve neurological outcome. We propose a modified scoring system to diagnose this entity as a basis for larger, multicenter studies.
PMID:41482158 | DOI:10.1016/j.jtct.2025.12.994