One (1) patient had a fatal neurologic event, cerebral hemorrhage/coma/leukoencephalopathy. This event was thought to be related to treatment with ARRANON.

Most nervous system events in the adult patients were eva luated as grade 1 or 2. The additional grade 3 events in adult patients, regardless of causality, were aphasia, convulsion, hemiparesis, and loss of consciousness, each reported in 1 patient (1%). The additional grade 4 events, regardless of causality, were cerebral hemorrhage, coma, intracranial hemorrhage, leukoencephalopathy, and metabolic encephalopathy, each reported in one patient (1%).

The other neurologic adverse events, regardless of causality, reported as grade 1, 2, or unknown in adult patients were abnormal coordination, burning sensation, disturbance in attention, dysarthria, hyporeflexia, neuropathic pain, nystagmus, peroneal nerve palsy, sciatica, sensory disturbance, sinus headache, and speech disorder, each reported in one patient (1%). 

Other Neurologic Events

There have also been reports of events associated with demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome. 

Adverse Reactions from Other Clinical Programs

In addition to the safety data from the pivotal clinical trials, tumor lysis syndrome has been observed (see PRECAUTIONS, General). 

OVERDOSAGE

There is no known antidote for overdoses of ARRANON. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death. In the event of overdose, supportive care consistent with good clinical practice should be provided.

Nelarabine has been administered in clinical trials up to a dose of 2,900 mg/m2 on days 1, 3, and 5 to 2 adult patients. At a dose of 2,200 mg/m2 given on days 1, 3, and 5 every 21 days, 2 patients developed a significant grade 3 ascending sensory neuropathy. MRI eva luations of the 2 patients demonstrated findings consistent with a demyelinating process in the cervical spine.

A single IV dose of 4,800 mg/m2 was lethal in monkeys, and was associated with CNS signs including reduced/shallow respiration, reduced reflexes, and fl