Introduction
Vincristine is at the core of many treatment protocols for childhood malignancies.
The major dose-limiting side effect is vincristine-induced peripheral neuropathy
(VIPN) which may cause morbidity and disrupt curative treatment. Several studies
have tried to identify pharmacogenetic biomarkers for susceptibility to
vincristine-induced toxicity (Egbelakin A et al., Pediatr Blood Cancer 2011;
56: 361–367. Aplenc R et al., Br J Haematol 2003; 122:
240–244. Diouf B et al., JAMA 2015; 313: 815–823. Zgheib NK
et al., Pharmacogenet Genomics, 2018; 28: 189–195. Gutierrez-Camino A
et al., Pharmacogenet Genomics 2016; 26: 100–102. Wright GE et al.,
Clin Pharmacol Ther 2019; 105: 402–410. Kayilioğlu H et
al., J Pediatr Hematol Oncol 2017; 39(6): 458–462). A major
limitation of these studies is that VIPN is difficult to measure objectively using
only clinical examination and clinical scales. This is especially true for children,
who are often unable to report or grade symptoms such as paresthesia, numbness, and
pain. Furthermore, some studies are questioning the validity of currently available
neuropathy grading scales (Postma TJ et al., Ann Oncol 1998; 9:
739–744). Our group recently showed that electrophysiological studies can be
used with great accuracy for early detection of VIPN (Kavcic M et al., J Pediatr
Hematol Oncol 2017; 39: 266–271). In the previous study, we found
that VIPN presents with primary axonal involvement and is more pronounced on motor
neurons (Kavcic M et al., J Pediatr Hematol Oncol 2017; 39:
266–271).
