ACUTE POLYNEUROPATHY AFTER HIGH-DOSE CYTOSINE-ARABINOSIDE IN PATIENTSWITH LEUKEMIA

BACKGROUND. Peripheral nerve toxicity has been reported but is not a c ommonly recognized complication of high dose cytosine arabinoside (HDA C) therapy. This study was undertaken to estimate the prevalence and d escribe the clinical spectrum of acute polyneuropathy associated with HDAC therapy for leukemia. METHODS. Records of 153 acute leukemia pati ents who received 194 courses of HDAC at the City of Hope were reviewe d for evidence of severe peripheral neuropathy with onset 2-3 weeks af ter HDAC therapy. RESULTS. Two patients were identified who developed motor disability 2-3 weeks after HDAC therapy, and the disability prog ressed in a monophasic course to quadriparesis. There was neurophysiol ogic evidence of peripheral nerve demyelination with slowed nerve cond uction velocities and conduction block. One patient who was autopsied had demyelination identified in luxol-fast blue sections of peripheral nerve (with Bielschowsky-stained sections showing intact peripheral n erve axons). There were foamy macrophages in the peripheral nerve but no chronic inflammatory cells. For comparison, data from these two pat ients were combined with those from four published case reports of pol yneuropathy associated with HDAC therapy. Quadriparesis occurred in fi ve of six cases with the need for ventilatory support in four. Cerebro spinal fluid protein was elevated in five of six cases. Etiologic evid ence incriminating HDAC included simultaneous cerebellar signs in two of six cases and a narrow interval of clinical onset after HDAC therap y. CONCLUSIONS. Demyelinating polyneuropathy occurs in approximately 1 % of HDAC courses and produces severe motor disability. HDAC immunosup pression could trigger an immune-mediated neuropathy; alternatively, a direct neurotoxic effect of HDAC on Schwann cells is also an etiologi c possibility. (C) 1996 American Cancer Society.