Severe central nervous system toxicity associated with the infusion of cryopreserved PBSC components

The infusion of PBSC or BM cells cryopreserved with DMSO is associated with frequent, but generally minor toxicity. The most severe toxicity is the rarely-occurring anaphylactic reaction. Neurological complaints, other than headache, have rarely been reported, except after infusion of very large quantities of DMSO.

We performed a retrospective chart-review of patients who experienced severe neurological toxicity during the infusion of PBSC components during the period of September 1992 through June 1998.

Ten patients developed severe neurological toxicity during, or shortly after the infusion of PBSC components cryopreserved in DMSO. The PBSC components were collected by standard apheresis procedures and concentrated to an average nucleated cell concentration of 6.9 x 10(8) cells/mL (range, 0.8-12.9 x 10(8) cells/mL), mononuclear cell concentration of 2.1 x 10(8) cells/mL (range, 0.2-6.8 x 10(8) cells/mL), and platelet concentration of 1.1 x 10(9) platelets/mL (range, 0.2-4.8 x 10(9) platelets/mL) before cryopreservation in 10% DMSO and autologous plasma of HSA. On the day of infusion, the patients were medicated with 50 mg of diphenhydramine and 250 mg of hydrocortisome. Most patients also received 12.5 g of mannitol. Six patients suffered seizures during the infusion. Three patients suffered syncope, or severe encephalopathy without obvious seizure activity. One patient suffered a transient ischemic attack (TIA) shortly after the infusion. The infusions were halted after these events occurred. The maximum amount of DMSO infused to any of these patients before the onset of the neurological event was 0.6 g/kg patient weight. Six patients received additional cryopreserved cells on the same or following day, without recurrence of the neurological event.

These 10 patients represent 0.9% of 1092 patients and 0.8% of 1328 infusions of cryopreserved PBSC components during the time-interval studied. The cause(s) of these events is not obvious and may include the addition of citrate anti-coagulant to the component after thawing the high cell concentrations used for cryopreservation.