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

Author:

Rodwin Rozalyn L1ORCID,Kairalla John A2,Hibbitts Emily2,Devidas Meenakshi3,Whitley Moira K1,Mohrmann Caroline E4,Schore Reuven J56,Raetz Elizabeth7,Winick Naomi J8ORCID,Hunger Stephen P9ORCID,Loh Mignon L10,Hockenberry Marilyn J1112,Angiolillo Anne L56,Ness Kirsten K13,Kadan-Lottick Nina S14ORCID

Affiliation:

1. Department of Pediatrics, Yale University School of Medicine , New Haven, CT, USA

2. Department of Biostatistics, Colleges of Medicine and Public Health & Health Professions, University of Florida , Gainesville, FL, USA

3. Department of Global Pediatric Medicine, St. Jude Children’s Research Hospital , Memphis, TN, USA

4. Department of Pediatrics, Washington University School of Medicine, St. Louis Children’s Hospital , St. Louis, MO, USA

5. Division of Oncology, Center for Cancer and Blood Disorders, Children’s National Medical Center , Washington, DC, USA

6. Cancer Biology Research Program, George Washington University School of Medicine and Health Sciences , Washington, DC, USA

7. Department of Pediatrics, NYU Langone Medical Center , New York, NY, USA

8. Department of Pediatrics, University of Texas Southwestern Medical Center , Dallas, TX, USA

9. Department of Pediatrics, Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA, USA

10. Department of Pediatrics, Benioff Children’s Hospital, and the Helen Diller Family Comprehensive Cancer Institute, University of California, San Francisco , San Francisco, CA, USA

11. Department of Pediatrics, Baylor College of Medicine , Houston, TX, USA

12. School of Nursing, Duke University , Durham, NC, USA

13. Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital , Memphis, TN, USA

14. Cancer Prevention and Control, Georgetown Lombardi Comprehensive Cancer Center , Washington, DC, USA

Abstract

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.

Funder

National Institutes of Health to the Children’s Oncology Group

NCTN Network Group Operations Center Grant

NCTN Statistics and Data Center

NCORP Grant for Cancer Control Studies

Clinical Oncology Research Program grant

National Cancer Institute Division of Cancer Prevention to COG

St. Baldrick’s Foundation

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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