To evaluate serum neurofilament light chain (sNfL) as a biomarker of axonal degeneration (AxD) in vincristine-induced peripheral neuropathy (VIPN).

Peripheral neuropathy is a frequent, dose-limiting complication of chemotherapy. Although axon-protective strategies, including inhibition of SARM1 (sterile alpha and TIR motif–containing protein 1), show promise in preclinical studies, clinical translation requires a practical biomarker to assess axonal degeneration, identify at-risk patients, and monitor therapeutic response. sNfL, a major axonal scaffolding protein, represents a promising candidate biomarker.

To assess associations between sNfL and clinical manifestations of VIPN, a cohort of twenty-nine patients with Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL) receiving vincristine-based chemotherapy (R-CHOP) were enrolled during the induction (n=14) or maintenance (n=15) phase of chemotherapy treatment. Signs and symptoms of peripheral neuropathy were assessed using validated instruments (EORTC-CIPN20, NCI-CTCAE, and TNSc). For induction-phase patients, sNfL was measured at baseline, one week after treatment initiation, and monthly thereafter. For maintenance-phase patients, sNfL was measured monthly during therapy.

In induction-phase patients, sNfL increased rapidly, peaking around a cumulative vincristine dose of 2mg, then plateaued around 5mg and declined. This rise preceded symptom onset, with EORTC-CIPN20 scores increasing around 9 mg and peaking near a cumulative dose of 16 mg. sNfL correlated with patient reported symptoms and muscle reflex scores on physical exam. In maintenance phase patients, mild, transient sNfL elevations were observed in 7/15 individuals, with all but one returning rapidly to baseline. sNfL correlated with sensory sub scores but not with overall instrument scores or physical exam scores. 

sNfL rises early in VIPN, preceding clinical symptoms, before peaking, and returning to baseline, suggesting axonal injury occurs early and progresses rapidly. sNfL correlates closely with symptoms in patients in the induction phase, but not in maintenance phase, likely because AxD is complete, yet patients are left with symptoms.