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与输注冷冻保存的 PBSC 成分相关的严重中枢神经系统毒性。

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

机构信息

Clinical Services for Blood and Blood Products, Fred Hutchinson Cancer Research Center, 100 Fairview Ave North, Seattle, WA 98109, USA.

出版信息

Cytotherapy. 1999;1(4):311-7.

PMID:20440908
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

DISCUSSION

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.

摘要

背景

含 DMSO 的 PBSC 或 BM 细胞冻存液输注相关的毒性通常较为轻微,但也较为频繁。最严重的毒性是偶发的过敏反应。除了输注大量 DMSO 后,很少有报告头痛以外的其他神经学症状。

方法

我们对 1992 年 9 月至 1998 年 6 月期间因输注含 DMSO 的 PBSC 成分而发生严重神经毒性的患者进行了回顾性病历审查。

结果

10 名患者在输注含 DMSO 的 PBSC 成分期间或输注后不久出现严重神经毒性。PBSC 成分通过标准的单采程序收集,浓缩至平均有核细胞浓度为 6.9 x 10(8)细胞/ml(范围为 0.8-12.9 x 10(8)细胞/ml),单个核细胞浓度为 2.1 x 10(8)细胞/ml(范围为 0.2-6.8 x 10(8)细胞/ml),血小板浓度为 1.1 x 10(9)个/ml(范围为 0.2-4.8 x 10(9)个/ml),在 10%DMSO 和自体人血白蛋白(HSA)中冷冻保存前。输注当天,患者给予 50mg 苯海拉明和 250mg 氢化可的松。大多数患者还接受了 12.5g 甘露醇。6 名患者在输注过程中出现癫痫发作。3 名患者出现晕厥或严重脑病而无明显癫痫发作活动。1 名患者在输注后不久发生短暂性脑缺血发作(TIA)。在这些事件发生后,停止了输注。这些患者在发生神经事件之前输注的最大 DMSO 量为 0.6g/kg 体重。6 名患者在同一日或次日接受了额外的冷冻保存细胞,未再发生神经事件。

讨论

这 10 名患者代表了研究期间 1092 名患者的 0.9%和 1328 次冷冻 PBSC 成分输注的 0.8%。这些事件的原因尚不清楚,可能包括解冻后成分中添加柠檬酸抗凝剂以及用于冷冻保存的高细胞浓度。

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