Response endpoints and failure-free survival after initial treatment for acute graft-versus-host disease
Response endpoints and failure-free survival after initial treatment for acute graft-versus-host disease
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DOI：
10.3324/haematol.2013.093062
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发表时间：
2014-02-01
期刊：
影响因子：
10.1
通讯作者：
Carpenter, Paul A.
中科院分区：
文献类型：
--
作者：
Inamoto, Yoshihiro;Martin, Paul J.;Carpenter, Paul A.
我们评估了急性移植物抗宿主病治疗试验的短期反应终点。我们假设，缓解终点应与症状负担减轻和后续治疗失败减少相关，治疗失败定义为非复发性死亡率、复发性恶性肿瘤或额外的全身治疗。该队列包括303名连续患者，他们接受了初始全身类固醇治疗急性移植物抗宿主病。在初始治疗后第28天评价反应，在所有情况下，这都发生在慢性移植物抗宿主病之前。在第28天，36%的患者有完全缓解，26%有非常好的部分缓解，10%有另一种程度的部分缓解（其他部分缓解），28%无缓解。正如预期，与其他部分缓解患者相比，部分缓解非常好的患者的症状负担较低。在完全缓解和非常好的部分缓解患者中，后续治疗失败的频率相似，但低于第28天其他部分缓解或无缓解的患者。部分缓解非常好的患者的二线治疗频率低于其他部分缓解的患者。与第28天完全缓解或非常好的部分缓解概率较低相关的风险因素是无关或人类白细胞抗原不匹配的相关供体移植物和初始治疗开始时的肝脏或胃肠道受累。总之，这些结果表明，急性移植物抗宿主病治疗试验的终点应区分非常好的部分缓解和其他部分缓解。我们的研究结果支持使用第28天的完全或非常好的部分缓解作为适当的短期主要终点。
We evaluated short-term response endpoints for acute graft-versus-host disease treatment trials. We postulated that response endpoints should correlate with reduced symptom burden and decreased subsequent treatment failure, defined as non-relapse mortality, recurrent malignancy, or additional systemic treatment. The cohort included 303 consecutive patients who received initial systemic steroid treatment for acute graft-versus-host disease. Response was evaluated at day 28 after initial treatment, which in all cases preceded the onset of chronic graft-versus-host disease. At day 28, 36% of patients had a complete response, 26% had a very good partial response, 10% had another degree of partial response (other partial response) and 28% had no response. As expected, the symptom burden was lower in patients with very good partial response compared to those with other partial response. The frequencies of subsequent treatment failure were similar in patients with complete and very good partial responses, but lower than in patients with other partial response or no response at day 28. The frequency of second-line treatment was lower in patients with very good partial response than in those with other partial response. Risk factors associated with a lower probability of complete or very good partial response at day 28 were unrelated or human leukocyte antigen-mismatched related donor grafts and liver or gastrointestinal involvement at onset of initial treatment. Taken together, these results suggest that endpoints in acute graft-versus-host disease treatment trials should distinguish between very good partial response and other partial response. Our results support the use of complete or very good partial response at day 28 as an appropriate short-term primary endpoint.