Neurofilament light chain as in vitro and clinical biomarker of vincristine-induced peripheral neuropathy.
Source: PubMed, NCBI / U.S. National Library of Medicine
Vincristine-induced peripheral neuropathy (VIPN) is a common side effect in children and adolescents treated with vincristine. Assessing VIPN, especially in young children, is challenging due to a lack of sensitive tools. This limits our understanding of the nature and risk factors of VIPN. This study aimed to investigate neurofilament light chain (NfL) as a biomarker of nerve damage in vitro and in vivo. Induced pluripotent stem cells (iPSC) were differentiated into sensory neurons (SN) and exposed to incremental concentrations of vincristine. Cells were fixed and immunolabelled to showcase structural damage and media were collected for assessment of NfL. Furthermore, we performed a prospective, self-controlled clinical trial in 21 children with acute lymphoblastic leukaemia (ALL) during their 36-day weekly vincristine induction and assessed VIPN symptoms using Common Terminology Criteria for Adverse Events (CTCAE). Blood was drawn before or shortly after initiating treatment and every week following initiation of treatment to assess NfL in serum (sNfL). In vitro studies using iPSC-SN showed that vincristine exposure caused substantial structural damage and a dose-dependent increase in NfL release to cell medium. In this pilot study, median sNfL increased from 8.9 pg/mL pre-treatment to 158.5 pg/mL by day 36, coinciding with worsening sensory and motor symptoms. However, in this pilot study, no statistically significant correlation between sNfL levels and CTCAE was
Abstract
Vincristine-induced peripheral neuropathy (VIPN) is a common side effect in children and adolescents treated with vincristine. Assessing VIPN, especially in young children, is challenging due to a lack of sensitive tools. This limits our understanding of the nature and risk factors of VIPN. This study aimed to investigate neurofilament light chain (NfL) as a biomarker of nerve damage in vitro and in vivo. Induced pluripotent stem cells (iPSC) were differentiated into sensory neurons (SN) and exposed to incremental concentrations of vincristine. Cells were fixed and immunolabelled to showcase structural damage and media were collected for assessment of NfL. Furthermore, we performed a prospective, self-controlled clinical trial in 21 children with acute lymphoblastic leukaemia (ALL) during their 36-day weekly vincristine induction and assessed VIPN symptoms using Common Terminology Criteria for Adverse Events (CTCAE). Blood was drawn before or shortly after initiating treatment and every week following initiation of treatment to assess NfL in serum (sNfL). In vitro studies using iPSC-SN showed that vincristine exposure caused substantial structural damage and a dose-dependent increase in NfL release to cell medium. In this pilot study, median sNfL increased from 8.9 pg/mL pre-treatment to 158.5 pg/mL by day 36, coinciding with worsening sensory and motor symptoms. However, in this pilot study, no statistically significant correlation between sNfL levels and CTCAE was found. Vincristine causes concentration-dependent NfL release in vitro, and sNfL levels increase during vincristine treatment. Further studies are needed to investigate sNfL's potential as a biomarker of VIPN in children with ALL.