Fatal Peripheral Neuropathy Associated With Axonal Degeneration After High‐dose Cytosine Arabinoside in Acute Leukaemia

Peripheral neuropathy caused by high-dose cytosine arabinoside treatment in a patient with acute myeloid leukemia

“…On average, two of ten patients studied developed peripheral neuropathy during the administration of Ara-C, 3,7 but any correlation of the duration/ dose of Ara-C with either the onset or the severity of the associated neuropathy was unclear. Clinical presentations also proved to be variable, and ranged from sensory to rapidly progressive polyneuropathy; [3][4][5][6][7][8][9] in these reports, [6][7][8][9] four patients had required ventilator support and three of them subsequently died with peripheral neuropathy. Only one of these patients, who received plasma exchange, showed a full recovery.…”

“…In 1985, Scherokman et al 3 first reported evidence of peripheral neuropathy following HDAC treatment, and to date, only nine such cases have been reported [3][4][5][6][7][8][9] (Table 1). The incidence of CNS toxicity in clinical trials of HDAC has been previously reported to be 8%-26%, with cerebellar toxicity proving to be the most common of the neurologic toxicities associated with Ara-C. 1 In contrast, Openshaw et al 9 reported that, in a retrospective analysis from one institute, peripheral neuropathy occurred in only 1% of patients who received HDAC.…”

“…10 On the other hand, several investigators previously reported the destruction of myelin sheaths and axonal degeneration in peripheral nerves after HDAC treatment. 5,6,8,9 It has been postulated that the mechanisms of the peripheral neuropathy were due to either direct drug toxicity, or possibly, autoimmune responses. Several investigators, using fetal animal models and in vitro studies, have reported that Ara-C exerts its effects by interfering with DNA synthesis in actively dividing neurons.…”