Acute polyneuropathy after high dose cytosine arabinoside in patients with leukemia.
BACKGROUND
Peripheral nerve toxicity has been reported but is not a commonly recognized complication of high dose cytosine arabinoside (HDAC) therapy. This study was undertaken to estimate the prevalence and describe the clinical spectrum of acute polyneuropathy associated with HDAC therapy for leukemia.


METHODS
Records of 153 acute leukemia patients who received 194 courses of HDAC at the City of Hope were reviewed for evidence of severe peripheral neuropathy with onset 2-3 weeks after HDAC therapy.


RESULTS
Two patients were identified who developed motor disability 2-3 weeks after HDAC therapy, and the disability progressed in a monophasic course to quadriparesis. There was neurophysiologic evidence of peripheral nerve demyelination with slowed nerve conduction 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 nerve axons). There were foamy macrophages in the peripheral nerve but no chronic inflammatory cells. For comparison, data from these two patients were combined with those from four published case reports of polyneuropathy associated with HDAC therapy. Quadriparesis occurred in five of six cases with the need for ventilatory support in four. Cerebrospinal fluid protein was elevated in five of six cases. Etiologic evidence incriminating HDAC included simultaneous cerebellar signs in two of six cases and a narrow interval of clinical onset after HDAC therapy.


CONCLUSIONS
Demyelinating polyneuropathy occurs in approximately 1% of HDAC courses and produces severe motor disability. HDAC immunosuppression could trigger an immune-mediated neuropathy; alternatively, a direct neurotoxic effect of HDAC on Schwann cells is also an etiologic possibility.
Department of Neurology, City of Hope National Medical Center, Durate, California 91010, USA.
H
H
Openshaw
N E
NE
Slatkin
A S
AS
Stein
D R
DR
Hinton
S J
SJ
Forman
D000208:Acute Disease; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D002526:Cerebellar Diseases / Q000139:chemically induced*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects*; D003711:Demyelinating Diseases / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D012189:Retrospective Studies
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine