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兔抗人胸腺细胞球蛋白水平高与移植物抗宿主病发生率低和移植后淋巴增殖性疾病发生率高相关。

High rabbit-antihuman thymocyte globulin levels are associated with low likelihood of graft-vs-host disease and high likelihood of posttransplant lymphoproliferative disorder.

机构信息

The University of Calgary and Alberta Health Services, Calgary, Alberta, Canada.

出版信息

Biol Blood Marrow Transplant. 2010 Jul;16(7):915-26. doi: 10.1016/j.bbmt.2010.02.027. Epub 2010 Mar 11.

Abstract

Rabbit-antithymocyte globulin (ATG) given with conditioning has the potential to decrease the likelihood of graft-versus-host disease (GVHD) or graft failure and to increase the likelihood of relapse or infections. After a given ATG dose, serum ATG levels are variable. Here we determined ATG levels on days 7 and 28 in 153 patients whose conditioning included 4.5 mg/kg ATG (thymoglobulin). Median follow-up was 547 days (range: 14-1519, minimum for patients who have not died, relapsed, developed second malignancy, or had graft failure, 365). Both high day 7 levels and high day 28 levels were associated with low likelihoods of grade II-IV acute GVHD and chronic GVHD needing systemic immunosuppressive therapy, and a high likelihood of posttransplant lymphoproliferative disorder (PTLD). Patients with day 7 ATG levels above 0.803 mg/L had 0.52-fold risk of developing chronic GVHD needing systemic therapy (P = 0.012) and patients with day 7 ATG levels above 1.436 mg/L had 5.84-fold risk of developing PTLD (P = 0.001) compared to patients with lower ATG levels. There was no association of ATG levels with relapse, death, or non-PTLD infections. Association with graft failure could not be evaluated due to only 4 graft failures in the cohort. In conclusion, patients with slow clearance of ATG have a low risk of GVHD, but a high risk of PTLD. The clearance of this relatively low dose of ATG does not impact the likelihood of relapse, death, or non-PTLD infections.

摘要

兔抗胸腺细胞球蛋白(ATG)与预处理联合应用具有降低移植物抗宿主病(GVHD)或移植物失败发生率、增加复发或感染发生率的潜力。在给予特定 ATG 剂量后,血清 ATG 水平存在差异。本研究在 153 例接受 4.5mg/kg ATG(胸腺球蛋白)预处理的患者中,分别于第 7 天和第 28 天检测 ATG 水平。中位随访时间为 547 天(范围:14-1519 天,未死亡、复发、发生第二恶性肿瘤或发生移植物失败的患者的最小随访时间为 365 天)。第 7 天和第 28 天 ATG 水平高与 II-IV 级急性 GVHD 和需要系统免疫抑制治疗的慢性 GVHD 发生率低以及移植后淋巴增殖性疾病(PTLD)发生率高相关。第 7 天 ATG 水平高于 0.803mg/L 的患者发生慢性 GVHD 需要系统治疗的风险是 ATG 水平较低患者的 0.52 倍(P=0.012),第 7 天 ATG 水平高于 1.436mg/L 的患者发生 PTLD 的风险是 ATG 水平较低患者的 5.84 倍(P=0.001)。ATG 水平与复发、死亡或非 PTLD 感染无关。由于该队列中仅发生 4 例移植物失败,因此无法评估 ATG 水平与移植物失败的关系。总之,ATG 清除缓慢的患者发生 GVHD 的风险较低,但发生 PTLD 的风险较高。该相对低剂量 ATG 的清除不影响复发、死亡或非 PTLD 感染的可能性。

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