Persistence of Chemotherapy-Induced Peripheral Neuropathy Despite Vincristine Reduction in Childhood B-Acute Lymphoblastic Leukemia

Abstract

Background: Children with B-acute lymphoblastic leukemia (B-ALL) are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Children's Oncology Group AALL0932 randomized reduction in vincristine and dexamethasone (every 4 weeks vs 12 weeks during maintenance in the average-risk subset of National Cancer Institute standard-B-ALL (SR AR B-ALL). We longitudinally measured CIPN, overall and by treatment group.

Methods: AALL0932 standard-B-ALL patients aged 3 years and older were evaluated at T1-T4 (end consolidation, maintenance month 1, maintenance month 18, 12 months posttherapy). Physical and occupational therapists (PT/OT) measured motor CIPN (hand and ankle strength, dorsiflexion and plantarflexion range of motion), sensory CIPN (finger and toe vibration and touch), function (dexterity [Purdue Pegboard], and walking efficiency [Six-Minute Walk]). Proxy-reported function (Pediatric Outcome Data Collection Instrument) and quality of life (Pediatric Quality of Life Inventory) were assessed. Age- and sex-matched z scores and proportion impaired were measured longitudinally and compared between groups.

Results: Consent and data were obtained from 150 participants (mean age = 5.1 years [SD = 1.7], 48.7% female). Among participants with completed evaluations, 81.8% had CIPN at T1 (74.5% motor, 34.1% sensory). When examining severity of PT/OT outcomes, only handgrip strength (P < .001) and walking efficiency (P = .02) improved from T1-T4, and only dorsiflexion range of motion (46.7% vs 14.7%; P = .008) and handgrip strength (22.2% vs 37.1%; P = .03) differed in vincristine and dexamethasone every 4 weeks vs vincristine and dexamethasone 12 weeks at T4. Proxy-reported outcomes improved from T1 to T4 (P < .001), and most did not differ between groups.

Conclusions: CIPN is prevalent early in B-ALL therapy and persists at least 12 months posttherapy. Most outcomes did not differ between treatment groups despite reduction in vincristine frequency. Children with B-ALL should be monitored for CIPN, even with reduced vincristine frequency.

Figure 1.

(A) Consort diagram for participants enrolled on Leukemia Physical Function Study. (B) Study schema and cumulative vincristine dose for SR AR B-ALL arm of Children’s Oncology Group AALL0932. ^aAssigned cumulative vincristine dose in VCR/DEX4 is 75 mg/m² in males and 55.5 mg/m² in females. ^bAssigned cumulative vincristine dose in VCR/DEX12 is 43.5 mg/m² in males and 37.5 mg/m² in females. ^cVincristine dose at T4 is the cumulative dose for male participants; cumulative dose for females is the same as T3. SR AR B-ALL = average-risk subset of National Cancer Institute standard-risk B-acute lymphoblastic leukemia; T1 = end consolidation; T2 = maintenance month 1; T3 = maintenance month 18; T4 = 12 months posttherapy; VCR/DEX4 = every 4-week vincristine and dexamethasone pulses in maintenance; VCR/DEX12 = every 12-week vincristine and dexamethasone pulses in maintenance.

Figure 2.

Proportion of participants with impaired A) motor, B) sensory, C) functional, and D) proxy-reported outcomes at T1 (end consolidation) through T4 (12 months posttherapy) compared with expected population impairment. ^aN for each evaluation is displayed in Supplementary Table 4 (available online). ^bExpected population impairment was calculated based on z score cutoffs used to define impairment and was 9.7% for z scores less than −1.3 and 2.3% for z scores less than −2.0. Expected population impairment was not calculated for dichotomous variables (light touch sensation). ^cIndicates proportion impaired was statistically significantly higher in study population at T4 than expected population impairment at a statistical significance level of .05. PedsQL = Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales; PODCI = Pediatric Outcomes Data Collection Instrument; ROM = range of motion; T1 = end consolidation; T2 = maintenance month 1; T3 = maintenance month 18; T4 = 12 months posttherapy.