Randomized clinical trial of thalidomide, cyclosporine, and prednisone versus cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease
Randomized clinical trial of thalidomide, cyclosporine, and prednisone versus cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease
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DOI：
10.1053/bbmt.2001.v7.pm11400948
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发表时间：
2001-01-01
影响因子：
4.3
通讯作者：
Weisdorf, DJ
中科院分区：
文献类型：
--
作者：
Arora, M;Wagner, JE;Weisdorf, DJ
慢性移植物抗宿主病（CGVHD）是同种异体骨髓移植后发病的主要原因。沙利度胺在高危或耐药性 CGVHD 的挽救治疗中具有活性。在一项前瞻性随机试验中，我们测试了沙利度胺的初始治疗。患有广泛 CGVHD 的患者随机接受环孢素和隔日泼尼松治疗（n = 27，无沙利度胺 [no-thal] 组）或环孢素、泼尼松和沙利度胺（200-800 mg/天；n = 27，thal 组）。尽管大多数患者有反应，但沙利度胺初始治疗并未改善 CGVHD 的控制。 thal 组和 no-thal 组的 2 个月缓解率分别为 83% 和 89% (P = .7)、6 个月时分别为 88% 和 84% (P > .8) 和 1 年时分别为 85% 和 73% (P = .5)。多变量分析显示，相关供体移植（比值比 [OR] = 11.3；P = .03）和 CGVHD 新发或静止发作（OR = 7.7；P = .04）是良好早期反应的显着预测因子，而血小板计数大于或等于 100,000/μL 是良好反应的显着预测因子（OR = 10.4；P = .04）。 1 年。 thal 组和 nothal 组的 1 年生存率（66% 对 74%）和 2 年生存率相似（66% 对 54%，P = 0.85）。多变量分析显示，进展性 CGVHD（相对风险 [RR] = 4.2；P = .01）、无关供者（RR = 5.7；P < .01）、性别不匹配（RR = 7.9；P < .01）和血小板计数 < 100,000/μL（RR = 3.8；P = .01）是较差生存的显着预测因素。这些数据表明，尽管沙利度胺具有很高的缓解率（79% 缓解和 53% 完全缓解）和令人鼓舞的生存率（1 年 70%，2 年 60%），但沙利度胺在纳入 CGVHD 初始治疗时没有提供临床益处。沙利度胺作为挽救治疗的价值需要进一步研究。
Chronic graft-versus-host disease (CGVHD) is a major cause of morbidity following allogeneic bone marrow transplantation. Thalidomide is active in salvage therapy for high-risk or resistant CGVHD. In a prospective randomized trial, we tested initial therapy with thalidomide. Patients with extensive CGVHD were randomized to receive either cyclosporine and alternate-day prednisone (n = 27, no-thalidomide [no-thal] group) or cyclosporine, prednisone, and thalidomide (200-800 mg/day; n = 27, thal group). Although most patients responded, initial therapy with thalidomide did not improve control of CGVHD. Response rates were 83% versus 89% at 2 months (P = .7), 88% versus 84% at 6 months (P > .8) and 85% versus 73% at 1 year (P = .5) in the thal and no-thal groups, respectively. Multivariate analysis revealed related donor transplant (odds ratio [OR] = 11.3; P = .03) and de novo or quiescent onset of CGVHD (OR = 7.7; P = .04) to be significant predictors of good early response, whereas a platelet count of greater than or equal to 100,000/muL was a significant predictor of good response (OR = 10.4; P = .04) at 1 year. Survival for the thal and nothal groups was similar at 1 year (66% versus 74%) and 2 years (66% versus 54%, P = .85). Multivariate analysis revealed progressive onset CGVHD (relative risk [RR] = 4.2; P = .01), unrelated donor (RR = 5.7; P < .01), sex mismatch (RR = 7.9; P < .01), and platelet counts of < 100,000/muL (RR = 3.8; P = .01) as significant predictors of poorer survival. These data suggest that despite a high response rate (79% response and 53% complete response) and encouraging survival rates (70% at 1 year and 60% at 2 years), thalidomide offers no clinical benefit when incorporated into initial therapy for CGVHD. The value of thalidomide as salvage therapy requires further study.