Abstract
Abstract 2819
Peripheral Neuropathy (PN) is a major side effect and dose-limiting factor of Bortezomib treatment in multiple myeloma (MM). The exact mechanism underlying Bortezomib induced PN (BIPN) is unknown, and the risk factors which increase susceptibility for developing this syndrome have yet to be elucidated. Brain Derived Neurotrophic Factor (BDNF) is a nerve growth factor which is responsible for the development, maintenance, and repair of the peripheral nervous system. Aim: In this work we examined alterations in the levels of BDNF in circulating blood and searched for their relation with BIPN development.
24 patients with Multiple Myeloma receiving Bortezomib based regimen and 30 patients with other hematological malignancies (OHM) were examined. We used ELISA to quantify soluble BDNF (sBDNF) level in patient's platelets-poor plasma (PPP) and flow cytometry or western blotting to quantify BDNF in platelets. PN was assessed and graded according to the cancer common toxicity criteria index.
The level of sBDNF in MM patients PPP at diagnosis was similar to the level of sBDNF in patients with other hematological malignancies at diagnosis (3.86±2.47 ng/ml Mean ± SD in MM and 3.70±2.5 ng/ml in OHM). During treatment with Bortezomib the level of sBDNF was reduced only in the group of MM patients that developed BIPN (1.94±1.7 ng/ml P value<0.05) whereas the level of sBDNF in MM patients who did not develop BIPN remained equal to the level at diagnosis. Correspondingly, a negative correlation between the level of sBDNF and the severity of BIPN was observed. Analysis of platelets, the main cellular storage of BDNF in the peripheral blood, revealed a high incidence of BDNF-containing platelets as well as increased BDNF content within platelets of patients with BIPN as compared to patients without BIPN. No difference in the number of platelets between patients with BIPN and patients without BIPN was observed.
Our results suggest that alterations in the circulating blood level of BDNF may play role in the pathophysiology of BIPN development. Detailed investigation regarding potential mechanisms by which BDNF is involved in BIPN is required. Furthermore, BDNF could serve as a useful biomarker for early detection of Bortezomib induced BIPN.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
