Depletion of nerve growth factor in chemotherapy-induced peripheral neuropathy associated with hematologic malignancies

PLoS One. 2017 Aug 21;12(8):e0183491. doi: 10.1371/journal.pone.0183491. eCollection 2017.

Abstract

Objective: To investigate whether the depletion of nerve growth factor (NGF) is associated with the development of chemotherapy-induced peripheral neuropathy (CIPN) in patients with hematologic malignancy.

Methods: We prospectively enrolled hematologic cancer patients who had a plan to receive bortezomib, thalidomide, or vincristine. Baseline NGF levels were measured within one week before the start date of chemotherapy. Follow-up NGF levels were measured after four months from the start date of chemotherapy or the date when CIPN was initially diagnosed.

Results: Baseline and follow-up NGF pairs were measured in 45 patients (male/female = 27/18, median age = 63 years old). CIPN has developed in 28 patients. In the CIPN group, the level of NGF was significantly decreased after chemotherapy compared to the baseline (△NGF = -3.52 ±5.72; p-value = 0.003), while the NGF level of the no-CIPN group was not changed after chemotherapy. The differences in △NGF levels between the CIPN and no-CIPN group were more profound when analyzed in the subgroup of newly diagnosed multiple myeloma patients (△NGF = -4.14 ± 4.87 pg/ml for the CIPN group and +2.52 ± 8.39 pg/ml for the no-CIPN group; p-value = 0.043).

Conclusions: This study shows that the depletion of NGF occurs during the development of CIPN, suggesting pathogenesis based on the role of NGF and therapeutic implications.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Female
  • Hematologic Neoplasms / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Nerve Growth Factor / blood*
  • Peripheral Nervous System Diseases / blood
  • Peripheral Nervous System Diseases / chemically induced*
  • Prospective Studies

Substances

  • Nerve Growth Factor

Grants and funding

This work was supported by the National Research Foundation of Korea(NRF) grants funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (2016R1C1B2011815, 2016M3C7A1914002). S.-T. Lee was supported by the SNUH Research Fund (0420150850). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.