Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial
Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial
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DOI：
10.1016/s1470-2045(09)70225-6
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发表时间：
2009-09-01
期刊：
影响因子：
51.1
通讯作者：
Socie, Gerard
中科院分区：
文献类型：
--
作者：
Finke, Juergen;Bethge, Wolfgang A.;Socie, Gerard
背景移植物抗宿主病(GVHD)是非血缘关系供者异基因造血细胞移植后发病率和死亡率的主要原因。抗T细胞球蛋白(ATGs)可降低GVHD的发生率。我们进行了一项前瞻性、随机、多中心、开放标签的3期试验，以比较标准GVHD预防与环孢菌素和甲氨蝶呤加或不加抗Jurkat ATG-Fresenius(ATG-F)的效果。方法2003年5月26日至2007年2月8日，202名血液系统恶性肿瘤患者采用计算机生成的中心分层区组随机分组，在接受环孢菌素和甲氨蝶呤加或不加ATG-F的治疗组之间进行集中随机分配。在ATG-F组中有1例患者未接受移植，因此201例接受清髓预适应后非血缘关系供者外周血(n=164；82%)或骨髓(n=37；18%)移植的患者进入FUN分析集，并按其随机分配的处理进行分析(ATG-F n=103，对照组n=98)。主要终点是严重急性移植物抗宿主病(AGVHD)III-IV级或移植后100天内死亡。该试验的登记编号为DRKS00000002和NCT00655343。结果发现，ATG-F组发生严重aGVHD III-IV级或在移植后100天内死亡的患者分别为12例和10例(21.4%，95%可信区间13.4-29.3)，而对照组分别为24例和9例(33.7%，24.3-43.0)(调整后优势比0.59，95%可信区间0.30-1.17；P=0.13)。AGVHD III-IV级的累积发生率在ATG-F组为11.7%(95%CI 6.8-19.8)，而对照组为24-5%(17.3-34.7)(调整后的危险比[HR]0.50，95%CI 0.25-1.01；p=0.054)，aGVHD II-IV级的累积发生率在ATG-F组为33.0%(n=34；95%CI 25.1-43.5)，而对照组为51.0%(n=50；对照组的95%可信区间为42.0-61.9(调整后的HR0.56，0.36-0.87；p=0.011)。广泛性慢性移植物抗宿主病的2年累积发病率为12.2%(n=11；95%可信区间为7.0~21.3)与42.6%(n=34；95%可信区间为33.0~55.0；调整后的HR为0.22，0.11~0.43；p
Background Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic haematopoietic cell transplantation from unrelated donors. Anti-T-cell globulins (ATGs) might lower the incidence of GVHD. We did a prospective, randomised, multicentre, open-label, phase 3 trial to compare standard GVHD prophylaxis with ciclosporin and methotrexate with or without anti-Jurkat ATG-Fresenius (ATG-F).Methods Between May 26, 2003, and Feb 8, 2007, 202 patients with haematological malignancies were centrally randomly assigned using computer-generated centre-stratified block randomisation between treatment groups receiving ciclosporin and methotrexate with or without additional ATG-F. One patient in the ATG-F group did not undergo transplantation, thus 201 patients who underwent transplantation with peripheral blood (n=164; 82%) or bone marrow (n=37; 18%) grafts from unrelated donors after myeloablative conditioning were included in the fun analysis set, and were analysed according to their randomly assigned treatment (ATG-F n=103, control n=98). The primary endpoint was severe acute GVHD (aGVHD) grade III-IV or death within 100 days of transplantation. The trial is registered with the numbers DRKS00000002 and NCT00655343.Findings The number of patients in the ATG-F group who had severe aGVHD grade III-IV or who died within 100 days of transplantation was 12 and 10 (21.4%, 95% CI 13.4-29.3), respectively, compared with 24 and nine (33.7%, 24.3-43.0) patients, respectively, in the control group (adjusted odds ratio 0.59, 95% CI 0.30-1.17; p=0.13). The cumulative incidence of aGVHD grade III-IV was 11.7% (95% CI 6.8-19.8) in the ATG-F group versus 24-5% (17.3-34.7) in the control group (adjusted hazard ratio [HR] 0.50, 95% CI 0.25-1.01; p=0.054), and cumulative incidence of aGVHD grade II-IV was 33.0% (n=34; 95% CI 25.1-43.5) in the ATG-F group versus 51.0% (n=50; 95% CI 42.0-61.9) in the control group (adjusted HR 0.56, 0.36-0.87; p=0.011). The 2-year cumulative incidence of extensive chronic GVHD was 12.2% (n=11; 95% CI 7.0-21.3) versus 42.6% (n=34; 95% CI 33.0-55.0; adjusted HR 0.22, 0.11-0.43; p