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

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 (Delta 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 Delta NGF levels between the CIPN and no-CIPN group were more profound when analyzed in the subgroup of newly diagnosed multiple myeloma patients (Delta 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.