De-escalating vincristine maintenance therapy can reduce neuropathy in children with acute lymphoblastic leukaemia, a first-of-its-kind study suggests.
The researchers conducted a sub-study of the randomised phase 3 UKALL 2011 trial, looking at the trajectory of vincristine-induced peripheral neuropathy (VIPN), a “common but incompletely characterised” complication of childhood ALL treatment, they said.
Of the 96 patients recruited for the substudy, 67 completed the necessary longitudinal neuropathy assessments to be included in the final analysis. Just over half of these participants were randomly assigned to not receive vincristine/dexamethasone pulses as maintenance following intensive induction therapy.
VIPN developed early, peaked after delayed treatment intensification with 51% of children experiencing clinically significant neuropathy, improved during maintenance therapy and persisted in 16% of patients at treatment completion.
Findings showed patients receiving pulses had persistently higher Total Neuropathy Score–Pediatric Vincristine Revised (TNS-PVr) scores (IRR 1.39 [95% CI,1.06 to 1.84]; P .019), with deficits remaining at the end of therapy.
Alternatively, patients assigned to vincristine/dexamethasone pulse omission were more likely to recover to a score of zero by the end of treatment.
More intensive vincristine therapy was associated with a greater neuropathy burden (IRR 2.18 [95% CI, 1.07 to 4.42]; P .032).
The researchers, led by paediatric haematologists and physiotherapists at Great Ormond Street Hospital in London, said this was the first randomised evidence that de-escalation of vincristine during maintenance reduced the VIPN burden.
“These findings align with a growing body of evidence favouring pulse omission to minimise late toxicity, positioning it as a modest, targeted, and feasible strategy to lower long-term neuropathy risk in selected patients,” the researchers said.
Meanwhile, gait analysis identified persistent abnormalities in walking function during and after treatment across 46 assessed children. These included significantly reduced velocity (walking speed), cadence (number of steps per minute) and step length compared with age-and sex-matched healthy peers.
These deficits improved after the most intensive treatment phases but only partially recovered by the end of treatment, the researchers noted.
“Such abnormalities may contribute to reduced physical activity, musculoskeletal complications, and impaired quality of life in survivors. Incorporating gait metrics alongside standardised neuropathy scores provides a quantitative, reproducible end point directly relevant to survivorship care,” they said.
They added wearable sensors and phone-based gait tracking could help do this.
A limitation of the study was the younger cohort of patients, with a median age of 8. The researchers said their findings might therefore be less generalisable to older adolescents and young adults, who were more often treated on high-intensity regimens and might experienced different neuropathy trajectories.
The findings were published in JCO Oncology Advances [link here].