National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.
National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.
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DOI：
10.1016/j.jtct.2021.06.001
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发表时间：
2021-10
影响因子：
3.2
通讯作者：
Paczesny S
中科院分区：
文献类型：
--
作者：
Wolff D;Radojcic V;Lafyatis R;Cinar R;Rosenstein RK;Cowen EW;Cheng GS;Sheshadri A;Bergeron A;Williams KM;Todd JL;Teshima T;Cuvelier GDE;Holler E;McCurdy SR;Jenq RR;Hanash AM;Jacobsohn D;Santomasso BD;Jain S;Ogawa Y;Steven P;Luo ZK;Dietrich-Ntoukas T;Saban D;Bilic E;Penack O;Griffith LM;Cowden M;Martin PJ;Greinix HT;Sarantopoulos S;Socie G;Blazar BR;Pidala J;Kitko CL;Couriel DR;Cutler C;Schultz KR;Pavletic SZ;Lee SJ;Paczesny S
慢性移植物抗宿主病（GVHD）可能与显著的发病率相关，部分原因是不可逆的纤维化，其影响身体功能（眼睛，皮肤，肺部表现）和死亡率（肺部，胃肠道表现）。在预防与慢性GVHD相关的严重发病率和死亡率方面的进展受到复杂且不完全理解的疾病生物学和缺乏预后生物标志物的限制。同样，高度病态表现的治疗进展仍然受到缺乏针对“不可逆”纤维化后遗症的有效器官特异性方法以及难以在患者数量较少的异质性疾病中进行临床试验的阻碍。本文件的目的是确定当前的差距，概述高度病态形式的慢性GVHD的研究目标的路线图，包括晚期皮肤硬化症，筋膜炎，肺，眼和胃肠道受累，并提出有效的试验设计策略。工作组提出以下建议：（1）在未来队列中对慢性GVHD进行临床和生物学分型，以描述高度病态疾病的发生率、预后因素、器官损害机制和临床演变，包括儿童的长期影响;（2）进行纵向多中心研究，采用共同定义和研究样本收集;（3）开发早期识别和治疗高度病态形式的慢性GVHD的新方法，特别是生物靶向治疗，特别关注纤维化变化;以及（4）建立针对与干预时间点相关的每种高度病态表现的临床试验的主要终点（早与晚）。替代终点，如身体功能或生活质量无进展和改善，可能适用于具有高度病态表现的患者的临床试验。最后，需要新的方法进行客观的反应评估和探索新的试验设计的小群体。
Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting “irreversible” fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.
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