Boga Can, Yeral Mahmut, Gereklioglu Ciğdem, Asma Suheyl, Maytalman Erkan, Aytan Pelin, Kozanoglu Ilknur, Sariturk Cagla, Ozdogu Hakan
Hematology Department, Adana Adult BMT Center, Faculty of Medicine, Başkent University, Ankara, Turkey.
Hematology Department, Adana Adult BMT Center, Faculty of Medicine, Başkent University, Ankara, Turkey.
Hematol Oncol Stem Cell Ther. 2018 Sep;11(3):149-157. doi: 10.1016/j.hemonc.2018.01.004. Epub 2018 Feb 20.
OBJECTIVE/BACKGROUND: Anti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F.
This was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups.
Although the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III-IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667-199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5).
Dose difference of rATG-F did not influence survival parameters; however, increasing the dose to 30 mg/kg seems to be effective for reducing cGVHD with an increase in infection rate requiring close monitoring of infections in AML patients who received myeloablative fludarabine/busulfan conditioning.
目的/背景：移植方案中包含的抗T淋巴细胞球蛋白费森尤斯（rATG-F；ATG-费森尤斯）和抗胸腺细胞球蛋白（即胸腺球蛋白）用于降低慢性移植物抗宿主病（cGVHD）风险或抑制同种异体移植排斥反应。现有的临床研究是在异质性患者群体中进行的，采用了不同的给药方案，包括干细胞来源。此外，ATG的药代动力学存在差异，尤其是rATG-F的临床有效剂量尚不完全清楚。本研究的目的是调查接受全相合同胞供者造血外周干细胞移植并给予两种不同剂量r-ATG-F的急性髓系白血病（AML）患者的临床结局。
这是一项于2005年7月至2016年7月期间进行的单中心回顾性病历审查。69例连续接受基于氟达拉滨和白消安预处理的移植的AML患者纳入研究。第1组患者在2013年之前接受15mg/kg体重的rATG-F（n = 46），第2组从2013年开始接受30mg/kg的rATG-F剂量以降低cGVHD（n = 23）。使用环孢素和甲氨蝶呤预防急性移植物抗宿主病（aGVHD）。比较两组的结局参数。
尽管推荐剂量的r-ATG-F导致cGVHD的累积发生率降低（27例[58.7%]对8例[34.8%]；p = 0.03），但也增加了1年时的感染率（3例[6.5%]对4例[17.4%]；p = 0.02）。两组在植入时间、aGVHD、复发、非复发死亡率和rATG-F相关毒性方面相似。Cox回归模型显示，aGVHD III-IV级与1年时非复发死亡率增加相关（风险比 = 18.2；95%置信区间，1.667 - 199.255；p = <0.02）。没有患者发生rATG-F相关的严重不良事件（通用术语标准4级或5级）。
rATG-F的剂量差异不影响生存参数；然而，将剂量增加到30mg/kg似乎对降低cGVHD有效，但会增加感染率，这需要对接受清髓性氟达拉滨/白消安预处理的AML患者的感染进行密切监测。
