Persistence of chemotherapy-induced peripheral neuropathy despite vincristine reduction in childhood b-acute lymphoblastic leukemia

BACKGROUND: Children with B-acute lymphoblastic leukemia (B-ALL) are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Children\u27s Oncology Group AALL0932 randomized reduction in vincristine/dexamethasone (every 4-week [VCR/DEX4] vs. 12-week [VCR/DEX12]) during maintenance in the average-risk subset of NCI standard-B-ALL (SR AR B-ALL). We longitudinally measured CIPN, overall, and by treatment group. METHODS: AALL0932 SR AR B-ALL patients ≥3 years old were evaluated at T1-T4 (end-consolidation, maintenance month-1, maintenance month-18, 12-months post-therapy). Physical/occupational therapists (PT/OT) measured motor CIPN (hand/ankle strength, dorsiflexion/plantarflexion range of motion [ROM]), sensory CIPN (finger/toe vibration and touch), and function (dexterity [Purdue Pegboard], 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/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\u3c.001) and walking efficiency (p=.02) improved from T1-T4 and only dorsiflexion ROM (46.7% vs. 14.7%, p=.008) and handgrip strength (22.2% vs. 37.1%, p=.03) differed in VCR/DEX4 vs. VCR/DEX12 at T4. Proxy-reported outcomes improved from T1 to T4 (P\u3c.001) and most did not differ between groups. CONCLUSIONS: CIPN is prevalent early in B-ALL therapy and persists at least 12-months post-therapy. 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

Assessment of proxy-reported responses as predictors of motor and sensory peripheral neuropathy in children with B-lymphoblastic leukemia

Chemotherapy-induced peripheral neuropathy (CIPN), a common condition in children with acute lymphoblastic leukemia, can be challenging to diagnose. Using data from Children\u27s Oncology Group AALL0932 physical function study, we sought to determine if parent/guardian proxy-reported responses from the Pediatric Outcomes Data Collection Instrument could identify children with motor or sensory CIPN diagnosed by physical/occupational therapists (PT/OT). Four variables moderately discriminated between children with and without motor CIPN (c-index 0.76, 95% confidence interval [CI]: 0.64-0.84), but sensory and optimism-corrected models had weak discrimination (c-index sensory models 0.65, 95% CI: 0.54-0.74). New proxy-report measures are needed to identify children with PT/OT diagnosed CIPN

Early Intervention in Low-Birth-Weight Premature Infants: Results Through Age 5 Years From the Infant Health and Development Program

Objective.—To evaluate the persistence of effects on health and development at age 5 years of the Infant Health and Development Program, an early childhood intervention that was provided to low-birth-weight (LBW) premature infants from neonatal discharge through age 3 years.Design.—Randomized, controlled, multicenter trial, stratified by two LBW groups: lighter (≤2000 g) and heavier (2001 to 2500 g).Setting.—Eight socioeconomically heterogeneous clinical sites.Participants.—Of 985 eligible infants weighing 2500 g or less and at 37 weeks' or less gestational age, 377 infants were randomly assigned to the intervention group and 608 to the follow-up only group. About two thirds of the infants in each group were in the lighter LBW stratum, and one third were in the heavier LBW stratum.Intervention.—The intervention group received home visits (from neonatal discharge through age 3 years) as well as center-based schooling (from 1 to 3 years of age). Children in both groups received pediatric surveillance.Main Outcome Measures.—Cognitive development, behavioral competence, and health status.Results.—At age 5 years, the intervention group had full-scale IQ scores similar to children in the follow-up only group. However, in the heavier LBW stratum, children in the intervention group had higher full-scale IQ scores (3.7 points higher; P=.03) and higher verbal IQ scores (4.2 points higher; P=.02). No significant differences between intervention and follow-up only groups in cognitive measures at age 5 years were noted in the lighter LBW infants. The intervention and follow-up groups were similar in behavior and health measures regardless of LBW stratum.Conclusion.—The early childhood intervention provided in the first 3 years of life had effects on heavier LBW premature infants' IQ and verbal performance at age 5 years that were not observed for lighter LBW premature infants. The intervention did not affect health or behavior at age 5 years in either LBW stratum.(JAMA. 1994;272:1257-1262