To assess the impact of the neurotoxicity of vinca-alkaloids on nerve fibres, including motor, small/large sensory and autonomic, in patients with malignant lymphoma. 

Chemotherapy-induced peripheral neuropathy is a frequent adverse consequence of anti-cancer treatment that severely impacts upon the quality of life of cancer survivors.

A cohort prospective study included 18 patients with malignant lymphoma (12 men, 6 women, median age 36, range: 23–51 yrs). Detailed clinical examination, pain questionnaires, nerve conduction studies, quantitative sensory testing (QST), lower leg skin-punch biopsy, corneal confocal microscopy (CCM) and spectral analysis of heart rate variability (SAHRV) were performed before therapy including V-A, and 6 months after the end of it.

In the course of chemotherapy, 14 patients (78%) reported sensitive symptoms, mainly in distal extremities; these led to V-A dose reduction. Nerve conduction studies performed 6 months after V-A therapy disclosed significant reductions of the amplitude of sensory nerve action potentials in 12 patients (67%); moreover 3 of them developed median nerve compression of mild to moderate severity. QST abnormalities were found in 13 patients (72%) compared to 8 patients before chemotherapy, while intra-epidermal nerve fibre density (IENFD) in skin biopsy and corneal innervation did not differ significantly from initial examination. However, nerve thinning and fragmentation in skin biopsy were observed in 4 patients. Most of the patients (75%) developed no significant autonomic dysfunction persisting for 6 months after V-A treatment, as confirmed by SAHRV.

The study confirmed the neurotoxicity of cumulative doses of V-A on the peripheral nervous system, predominantly affecting the large sensory fibres. Skin biopsy and CCM did not demonstrate significant reduction of small fibres. Some structural changes in intra-epidermal innervation, however, were detected, which appear to indicate incipient degeneration of the terminals of small-nerve fibres.