Intravenous Busulfan, Dimethylacetamide and neurotoxicity after high-dose pretransplant conditioning chemotherapy

Abstract Intravenous Busulfan-based (IV Bu-) conditioning regimens are widely used in stem cell transplant and have been demonstrated as more effective and safer than cyclophosphamide and total body irradiation. Despite its superiority concerns remain regarding toxicities, specifically, veno-occlusive disease/sinusoidal obstructive syndrome, reproductive toxicity and neurotoxicity. Some of these concerns do not relate to busulfan itself, but to its composite solvent vehicle including N,N‑dimethylacetamide (DMA). Herein, we report a case series of six patients who received high-dose IV Bu-based conditioning regimens, and who developed neurotoxicity with various neurological manifestations and outcomes, ranging from mild to fatal. This case series highlights the need for further studies to investigate the safety of IV Bu, especially in patients with an underlying organic brain disorder, who have been treated with immunoconjugates with a potential for central neurotoxicity, or who have received therapeutic brain irradiation.