Severe neurological impairment with optic radiation-predominant leukoencephalopathy after fludarabine-based allogeneic hematopoietic stem cell transplantation: a three-case report

Fludarabine is widely used in conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). While myelosuppression is a well-recognized adverse effect of fludarabine, fludarabine-associated central nervous system toxicity is rare but potentially fatal and may be under-recognized in clinical practice. Herein, we report three cases of severe neurological impairment after allo-HSCT with fludarabine-based conditioning. All the patients had multiple risk factors including extensive prior cytotoxic therapy and renal dysfunction. Neurological symptoms were characterized by progressive impairment of consciousness, and two patients developed visual disturbances. Brain magnetic resonance imaging revealed bilateral, symmetric white matter lesions involving the periventricular white matter and optic radiation with restricted diffusion. Cerebrospinal fluid analysis revealed elevated protein levels in all the patients, with increased myelin basic protein levels in two of the patients, suggesting active demyelination. All the patients developed progressive renal dysfunction after fludarabine administration, which required dialysis, suggesting that dynamic changes in renal function may contribute to increased drug exposure and neurotoxicity. Although limited by the small number of cases, our findings highlight the importance of recognizing fludarabine-associated neurotoxicity as a differential diagnosis of neurological complications after allo-HSCT, particularly in high-risk patients.