D Przepiorka, C F LeMaistre, Y O Huh, M Luna, E A Saria, C T Brown, R E Champlin
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引用次数: 0
摘要
抗cd5蓖麻毒素A链免疫偶联物(XZ-CD5)是一种在体外抑制对同种异体抗原的增殖和细胞毒性反应的免疫毒素,在治疗急性移植物vs中具有活性。-宿主病(GVHD)。为了确定XZ-CD5是否可以用于预防急性GVHD, 11例接受同种hla异体骨髓移植的成人患者在移植后早期接受XZ-CD5 0.1 mg kg-1 day-1静脉注射高剂量甲基强的松龙10、14或17次。另外6名患者接受了17剂XZ-CD5和环孢素(CSA)。所有患者都进行了移植。严重毛细血管渗漏综合征是最常见的严重毒性,在接受CSA的患者中发生率更高(5/5 vs 3/11, P = 0.03)。所有可评估的患者均发展为急性GVHD;88%为II-IV级GVHD。流式细胞分析显示,在给药XZ-CD5期间和给药后早期,有大量的循环CD5+和CD3+淋巴细胞。这些结果表明,在这种情况下,免疫毒素并没有消除同种异体反应性T细胞。
Evaluation of anti-CD5 ricin A chain immunoconjugate for prevention of acute graft-vs.-host disease after HLA-identical marrow transplantation.
Anti-CD5 ricin A chain immunoconjugate (XZ-CD5) is an immunotoxin that inhibits proliferative and cytotoxic responses to alloantigen in vitro and has activity in the treatment of acute graft-vs.-host disease (GVHD). To determine if XZ-CD5 could be used to prevent acute GVHD, 11 adult recipients of HLA-identical allogeneic marrow received XZ-CD5 0.1 mg kg-1 day-1 intravenously with high-dose methyl-prednisolone for 10, 14 or 17 doses early post-transplant. Six additional patients received 17 doses of XZ-CD5 and cyclosporine (CSA). All patients engrafted. Severe capillary leak syndrome was the most common serious toxicity and occurred more frequently in patients receiving CSA (5/5 vs. 3/11, P = 0.03). All evaluable patients developed acute GVHD; 88% had grade II-IV GVHD. Flow cytometric analysis demonstrated a substantial number of circulating CD5+ and CD3+ lymphocytes during and early after administration of XZ-CD5. These results suggest that the immunotoxin did not eliminate alloreactive T cells in this setting.