Clinical toxicity of cryopreserved bone marrow graft infusion.
Clinical toxicity of cryopreserved bone marrow graft infusion.
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DOI：
10.1182/blood.v75.3.781.bloodjournal753781
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发表时间：
1990-02
期刊：
影响因子：
20.3
通讯作者：
Davis Jm;S. Rowley;H. Braine;S. Piantadosi;G. Santos
中科院分区：
文献类型：
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作者：
Davis Jm;S. Rowley;H. Braine;S. Piantadosi;G. Santos
我们前瞻性地评估了82例自体骨髓移植受者的输注相关毒性。移植物在10%二甲亚砜中低温保存，液氮保存。所有移植物均浓缩，收集褐皮细胞。体外用100微克/毫升的4-氢过氧环磷酰胺（4-HC）处理47例移植物；对26个移植物进行密度梯度分离处理，并用60微克/毫升的4-HC处理。9个褐皮浓缩物未经药物处理冷冻。输液前给予甘露醇、氢化可的松、苯海拉明。移植物迅速解冻并立即灌注，无需进一步操作。在输注期间，33名（70%）接受治疗的白毛受者、5名（56%）未接受治疗的白毛受者和6名（23%）接受密度梯度分离移植物的受者出现了不同的症状，包括恶心、腹部痉挛和潮红。在移植物输注后，83%接受治疗的黄皮浓缩物的强制肺活量下降；其中6名患者主诉呼吸困难，1名患者出现急性呼吸失代偿。98%接受治疗的黄皮细胞患者心率下降，45%无症状性心动过缓。该组45例患者（96%）出现过一过性高血压，其中18例（38%）在输液后6小时内需要额外的药物来控制血压。在未处理的黄皮浓缩物的接受者中观察到类似的心血管变化。一名未经处理的黄皮浓缩物的接受者在移植物输注后出现2度的心脏传导阻滞。23名（88%）接受密度梯度分离移植的患者心率下降，21名（81%）血压升高。然而，其变化程度小于经处理的黄皮细胞受体（P < 0.01）。强制肺活量不受输注密度梯度分离移植物的影响。两组患者均未发生肾功能衰竭或明显溶血事件。轻微到中度的毒性与低温保存的移植物输注有关。不论是治疗组还是未治疗组，与密度梯度分离移植组相比，黄皮分离移植组出现了更多的并发症。这些毒性可能与注入的冷冻保护剂和细胞裂解产物的体积有关，对于高度纯化的密度梯度分离的移植物来说，这些毒性较少。
We prospectively evaluated infusion-related toxicities in 82 recipients of autologous bone marrow grafts. The grafts were cryopreserved in 10% dimethylsulfoxide and stored in liquid nitrogen. All grafts were concentrated and buffy-coat cells were collected. Forty-seven grafts were treated ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 100 micrograms/mL; 26 grafts were further processed using density-gradient separation and treated with 4-HC at 60 micrograms/mL. Nine buffy-coat concentrates were frozen without drug treatment. Before infusion, patients were medicated with mannitol, hydrocortisone, and diphenhydramine. Grafts were rapidly thawed and immediately infused without further manipulation. During the infusions, 33 (70%) recipients of treated buffy-coat, 5 (56%) recipients of untreated buffy-coat, and 6 (23%) recipients of density-gradient separated grafts experienced varying symptoms including nausea, abdominal cramping, and flushing. Forced vital capacities for 83% of the recipients of treated buffy-coat concentrates decreased after the graft infusion; six of these patients complained of dyspnea and one patient experienced an acute episode of respiratory decompensation. Decreased heart rates were observed in 98% of the recipients of treated buffy-coat cells with asymptomatic bradycardia occurring in 45%. Forty-five patients (96%) in this group experienced transient hypertension, with 18 (38%) requiring additional medications within 6 hours after the infusion for control of blood pressure. Similar cardiovascular changes were observed in the recipients of untreated buffy-coat concentrates. One recipient of an untreated buffy-coat concentrate had 2 degrees heart block after the graft infusion. Twenty-three (88%) recipients of density-gradient separated grafts had decreased heart rates and 21 (81%) had increased blood pressure. However, the degrees of change were less than those experienced by the recipients of treated buffy-coat cells (P less than .01). Forced vital capacities were not affected by the infusion of the density-gradient separated grafts. No renal failure or obvious hemolytic episodes occurred for any patient group. Minor to moderate toxicities were associated with cryopreserved graft infusions. Recipients of buffy-coat separated grafts, both treated and untreated, experienced more complications than the recipients of density-gradient separated grafts. These toxicities may relate to the volumes of cryoprotectant and cell lysis products infused, which were less for the more highly purified density-gradient separated grafts.