The NIH consensus criteria for chronic graft-versus-host disease: far more than just another classification
The NIH consensus criteria for chronic graft-versus-host disease: far more than just another classification
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作者：
G. Socié
慢性移植物抗宿主病(CGVHD)是一种多器官疾病，是造血干细胞移植后晚期无复发死亡的主要原因。多年来，人们已经知道，尽管这种疾病通常在移植后100多天出现，但也可能出现更早的疾病发作。更重要的是，造血干细胞移植后100天以上具有典型急性GVHD特征的临床症状越来越多地被认识到，特别是近年来随着降低强度预适应方案的发展。2此外，急性移植物抗宿主病患者可进展为cGVHD，同时伴有急性移植物抗宿主病和慢性移植物抗宿主病的症状。多年来，我们一直使用西雅图集团开发的有限GVHD与广泛GVHD的分级系统。这项研究旨在确定需要全身免疫抑制的患者，但它没有反映单个器官受累的严重程度。虽然已经提出了其他分级方案(Lee SJ 4中的综述)来预测cGVHD后的存活率，但所有方案都缺乏对确定疾病总体严重程度的每个器官的一致评分和评估。认识到这些局限性，由美国国立卫生研究院(NIH)的Pavletic博士领导的一个专家小组于2004年召开了一次关于cGVHD的共识会议。由于所有与会者都认为迫切需要废除cGVHD(超过第100天的任何GVHD)的正式定义，NIH关于cGVHD 5的共识发展项目的诊断和分期工作组提出了诊断(表1)、器官评分和cGVHD严重程度的全球评估的标准标准(有关如何对器官严重程度进行评分和指定严重程度的详细信息，请参阅参考文献5)。为了评估NIH关于cGVHD的共识标准的适用性，Cho等人。在这一期的白血病中，1研究了211名异基因移植后100天以上发生移植物抗宿主病的患者，并根据NIH标准进行了重新分类。分类为晚期急性移植物抗宿主病(21%)、重叠综合征(30%)和经典型移植物抗宿主病(49%)。使用修订的西雅图标准和NIH全球评分对167例典型cGVHD和重叠综合征患者进行分级。这是使用严格的NIH疾病标准解决cGVHD剩余临界点的最大规模的研究。关于同一主题的另外两项研究已经发表：一项由纳什维尔小组涉及110名患者6，另一项由明尼阿波利斯小组涉及54名患者。两项研究中的7种分类分别为晚期急性移植物抗宿主病(36%和15%)、重叠综合征(26%和28%)和经典型移植物抗宿主病(37%和57%)(分别来自参考文献6和7的估计)。尽管不是基于相同的患者数量，并包括不同的患者、疾病和移植特征，因此可以合理地假设，根据西雅图第100天的里程碑，大约20%的正式归类为‘慢性’GVHD的患者实际上可以被认为具有急性炎症性疾病的特征。这纯粹是语义上的吗？我不这么认为。这意味着目前发表的所有估计都低估了急性移植物抗宿主病的发病率，而高估了慢性移植物抗宿主病的发病率。如果你意识到这一点，这并不重要；然而，重要的是，你是否想要使用这些发生率来计算临床试验的力量，或者你是否想要搜索急性移植物抗宿主病和慢性移植物抗宿主病复发(GVL效应)之间的统计联系。Cho博士的研究中有一个有趣的结果，即晚期急性移植物抗宿主病患者和…患者在移植物抗宿主病特异性存活率方面没有差异
Chronic graft-versus-host disease (cGVHD), a multi-organ disorder, is the leading cause of late nonrelapse mortality after hematopoietic stem cell transplant. It has been known for many years that although the disease usually manifests itself more than 100 days after transplant, earlier disease onset could occur. More importantly, clinical syndromes with features of typical acute GVHD are increasingly recognized beyond 100 days after hematopoietic stem cell transplant, especially in recent years with the development of the reduced-intensity conditioning regimen. 2 In addition, patients with acute GVHD may progress to developing cGVHD with symptoms of both acute GVHD and cGVHD. For many years, we have used a grading system, developed by the Seattle group, 3 of limited versus extensive GVHD. This study was designed to identify patients needing systemic immune suppression, but it does not capture the severity of individual organ involvement. Although other grading schemes have been proposed (review in Lee SJ 4) to predict survival following cGVHD, all lack consistent scoring and assessment of each organ involved in determining the overall severity of the disease. Recognizing these limitations, a group of experts led by Dr Pavletic at the National Institutes of Health (NIH) met in 2004 for a consensus conference on cGVHD. As all participants agreed that it was urgently necessary to get rid of the formal definition of cGVHD (any GVHD beyond day 100), the diagnosis and staging working group of the NIH Consensus Development Project on cGVHD 5 proposed standard criteria for diagnosis (Table 1), organ scoring and global assessment of cGVHD severity (see reference 5 for details on how to score organ severity and to assign a severity grade). To assess the applicability of NIH consensus criteria for cGVHD, Cho et al. in this issue of Leukemia 1 studied 211 patients who developed GVHD more than 100 days after allogeneic transplantation and who were reclassified using the NIH criteria. Classifications were late acute GVHD (21%), overlap syndrome (30%) and classic cGVHD (49%). Classic cGVHD and overlap syndrome patients (n= 167) were graded using both the revised Seattle criteria and NIH global scoring. This is the largest study addressing the critical point of what is left with cGVHD using stringent NIH disease criteria. Two other studies have been published on the same subject: one by the Nashville group involving 110 patients 6 and the other by the Minneapolis group involving 54 patients. 7 Classifications in both studies were late acute GVHD (36 and 15%), overlap syndrome (26 and 28%) and classic cGVHD (37 and 57%)(estimates from references 6 and 7, respectively). Despite not being based on the same patient numbers and including different patient, disease and transplant characteristics, one can thus reasonably assume that approximately 20% of patients formally classified as ‘chronic’GVHD using the Seattle day 100 landmark could in fact be considered as having features of an acute inflammatory disease. Is that purely semantic? I do not believe so. This means that all estimates currently published in the literature underestimate acute GVHD incidence and overestimate that of cGVHD. This is not of major importance if you are aware of this caveat; however, it is of importance whether you want to use these incidences to calculate the power of a clinical trial or whether you want to search for a statistical link between acute GVHD and cGVHD with relapse (GVL effect), for example. An intriguing result in Dr Cho’s study is the lack of difference in GVHD-specific survival between patients with late acute GVHD and those with …