Vincristine-Induced Neuropathy in UKALL 2011: Effects of Vincristine/Dexamethasone Pulse Omission and Prospective Gait Outcomes
Lucy Alderson, Lucy Waller, Mario Cortina-Borja, Vickyanne Carruthers, David Jamieson, John Moppett, Sheena Guram, Rachael Hough, Amy Kirkwood, Pam Kearns, Amrana Qureshi, Susan Baird, Jayashree Motwani, Nicholas Goulden, Ajay Vora, Gareth Veal, Sujith SamarasinghePURPOSE
Vincristine-induced peripheral neuropathy (VIPN) is a frequent, disabling complication of ALL therapy, yet its trajectory and risk factors remain incompletely defined. We prospectively evaluated VIPN, focusing on the impact of omitting vincristine/dexamethasone maintenance pulses and the utility of gait analysis as a functional end point.
METHODS
This substudy was embedded within UKALL 2011. In all, 96 participants were enrolled; of these, 67 completed sufficient longitudinal neuropathy assessments without relapse and were included in the primary analyses, and 39 were randomly assigned to maintenance vincristine/dexamethasone pulses or no pulses. Participants age ≥5 years underwent Total Neuropathy Score–Pediatric Vincristine Revised (TNS-PVr) assessments at predefined time points from baseline to end-of-treatment. In addition, 46 participants underwent gait analysis using the GAITRite walkway, standardized to age- and sex-matched norms. Mixed-effects models estimated incidence rate ratios (IRRs) for neuropathy burden and explored pharmacogenomic associations.
RESULTS
VIPN peaked after delayed intensification (51% with clinically significant neuropathy; TNS-PVr ≥5), improved during maintenance, and persisted in 16% at therapy completion. Gait analysis showed significantly reduced velocity, cadence, and step length versus norms (step length, –0.95 [95% CI, –1.14 to −0.76];
CONCLUSION
VIPN is common, peaks during intensive phases, and persists in a minority at therapy completion. Our results provide randomized evidence that pulse omission reduces neuropathy burden, whereas gait analysis offers an objective end point to guide future ALL protocols and survivorship assessment.