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Switching to Bortezomib may Improve Recovery From Severe Vincristine Neuropathy in Pediatric Acute Lymphoblastic Leukemia

Joshi, Jaitri; Tanner, Lynn PT; Gilchrist, Laura PT, PhD; Bostrom, Bruce MD

Journal of Pediatric Hematology/Oncology: August 2019 - Volume 41 - Issue 6 - p 457–462
doi: 10.1097/MPH.0000000000001529
Original Articles
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Purpose: The purpose of this study was to evaluate the impact of switching patients being treated for acute lymphoblastic leukemia (ALL) from vincristine to bortezomib.

Patients and Methods: A total of 20 patients with ALL were switched from vincristine to bortezomib (1.3 mg/m2/dose) because of worsening neuropathy despite physical therapy interventions (n=18) or at increased risk of neuropathy (n=2). Relapse rates were compared with 56 vincristine-only patients matched by prognostic factors. Maintenance blood counts in bortezomib patients were compared with cooperative group data using vincristine during maintenance. In addition, 6 evaluable patients were assessed for neuropathy using the pediatric-modified total neuropathy score. Neuropathy scores were collected during treatment with vincristine and after switching to bortezomib.

Results: After a median follow-up of 3.5 years the relapse rate in patients switched to bortezomib was nonsignificantly different than those remaining on vincristine. Patients on monthly bortezomib had statistically significantly lower platelet counts that did not require transfusions or dose adjustment. Total neuropathy for all 6 cases decreased significantly when switched to bortezomib from vincristine (P=0.015), with motor neuropathy declines in 5 of 6 subjects.

Conclusions: Bortezomib substitution for vincristine in ALL treatment is a potential strategy to mitigate severe vincristine neuropathy. These findings should be confirmed in a randomized clinical trial to further assess benefits and risks of this approach.

Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN

J.J. was a high school senior at the time of this work.

Off label use of bortezomib: like most drugs we use in pediatrics, bortezomib is not FDA approved in patients under the age of 18 nor is approved for ALL. However, there are numerous published papers on it use and ongoing clinical trials of bortezomib in ALL.

The authors declare no conflict of interest.

Reprints: Bruce Bostrom, MD, Children’s Hospitals and Clinics of Minnesota, 2525 Chicago Avenue, CSC 175, Minneapolis, MN 55404 (e-mail: bruce.bostrom@childrensmn.org).

Received October 9, 2018

Accepted May 7, 2019

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