Banking on a cooperative effort.
Banking on a cooperative effort.
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依靠合作努力。
DOI：
10.1080/10428194.2019.1654098
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发表时间：
2019
影响因子：
2.6
通讯作者：
Chung,StephenS
中科院分区：
文献类型：
--
作者：
Chung,StephenS
骨髓增生异常综合征（MDS）是一种以外周血细胞减少和进展为急性髓性白血病（AML）的风险增加为特征的克隆性疾病。尽管在过去的二十年中，我们对MDS的基因组学和生物学的理解有了显著的提高，但患者的治疗选择仍然有限，同种异体移植仍然是唯一的治疗方法。此外，包括低甲基化药物、来那度胺、生长因子和铁螯合在内的非移植治疗策略的最佳部署仍在争论中。由于公认的患者间异质性，对MDS生物学和患者个性化护理决策的更全面理解在很大程度上受到了阻碍。虽然利用临床和分子特征来分析异质性和预测临床结果已经取得了重大进展[2,3]，但目前使用的预后评分系统，如IPSS-R，主要是基于回顾性数据的推断。这些数据并没有完全捕捉到可能与了解疾病发生和进展相关的流行病学特征，以及可能对有效治疗决策至关重要的生活质量指标。此外，MDS生物标本库用于了解疾病异质性的生物学基础在很大程度上仅限于学术中心，因此可能偏向于参加临床试验的患者和疾病较晚期的患者。利用从患者身上获得的系列标本进行的有限数量的现有研究为疾病干细胞生物学、疾病进化和治疗耐药机制提供了强有力的见解[4,5]。一个更协调一致的努力，前瞻性地收集系列和良好注释的疾病标本将是至关重要的，使新的机制见解。据报道，MDS的发病率从2001-2003年的每10万人3.3例上升到近年来的每10万人5.3-13.1例。虽然这种增加可能部分反映了一般人群的老龄化，因为MDS与年龄之间有很强的相关性，但一个重要的因素也可能是MDS意识的提高和社区中心病例确诊的增加。确定预后标准和临床管理策略是否主要适用于向学术机构提交报告的人群，这将是很重要的。在这一期的《白血病和淋巴瘤》中，Sekeres等人描述了为国家MDS自然历史研究筛选的前200名患者，该研究是由国家心脏、肺和血液研究所（NHLBI）发起的一项协调一致的多机构努力，包括国家癌症研究所（NCI）支持的学术医疗中心和社区实践。这项工作的目标是招募疑似MDS的患者，并确定多达2000名MDS患者和500名特发性未确定意义细胞减少症（ICUS）患者，对所有确诊为MDS的患者进行前瞻性随访，以及更有限的ICUS患者队列。主要特点包括广泛和统一的生物标本收集和全面的集中临床数据库，包括广泛收集流行病学数据和记录患者报告的结果（PROs）。MDS工作的核心是确保诊断共识的工作流程，利用现场和集中的血液病理学家，在意见不一致的情况下，由第三位血液病理学家裁决诊断。这本身就揭示了25%的临床有意义的差异。
The myelodysplastic syndromes (MDS) are clonal disorders characterized by peripheral blood cytopenias and an increased risk for progression to acute myeloid leukemia (AML). Despite significant improvements in our understanding of the genomics and biology of MDS over the past two decades, therapeutic options for patients remain limited, with allogeneic transplantation remaining the only curative therapy [1]. Additionally, the optimal deployment of non-transplant treatment strategies including hypomethylating agents, lenalidomide, growth factors, and iron chelation remains under debate. Achieving a more complete understanding of MDS biology and personalizing care decisions for patients has been largely hampered by well-recognized inter-patient heterogeneity. While major strides have been made using clinical and molecular features to parse heterogeneity and predict clinical outcomes [2, 3], currently used prognostic scoring systems such as the IPSS-R are based largely on extrapolations from retrospective data. Such data do not fully capture epidemiologic features that may be relevant for understanding disease development and progression, as well as quality of life metrics that may be critical for effective therapeutic decision-making. Additionally, banking of MDS biospecimens to understand the biology underlying disease heterogeneity has largely been restricted to academic centers and as such may be biased towards patients enrolled in clinical trials and patients with more advanced disease. The limited number of existing studies utilizing serial specimens obtained from patients has contributed powerful insights into disease stem cell biology, disease evolution, and mechanisms of resistance to therapy [4, 5]. A more concerted effort to prospectively collect serial and well-annotated disease specimens will be crucial to making new mechanistic insights.The reported incidence of MDS has increased from 3.3 per 100,000 in 2001-2003 to 5.3-13.1 per 100,000 in recent years [6]. Although this increase may in part reflect the aging of the general population given the strong association between MDS and age, a significant factor may also be an improved awareness of MDS and increased ascertainment of cases from community centers. It will be important to determine whether prognostic criteria and clinical management strategies developed primarily in populations presenting to academic institutions will be applicable to such community based populations. In this issue of Leukemia and Lymphoma, Sekeres et al.[7] describe the first 200 patients screened for the National MDS Natural History Study, a concerted multi-institutional effort initiated by the National Heart, Lung, and Blood Institute (NHLBI) including National Cancer Institute (NCI) supported academic medical centers and community practices. The goal of this effort is to recruit patients with a suspected diagnosis of MDS and to identify up to 2,000 patients with MDS and 500 patients with idiopathic cytopenias of undetermined significance (ICUS), with prospective follow-up of all patients confirmed to have MDS, as well as a more limited cohort of patients with ICUS. Key features include extensive and harmonized biospecimen collection and a comprehensive centralized clinical database, including collection of extensive epidemiologic data and recording of patient-reported outcomes (PROs). Central to such an effort in MDS is a workflow to ensure consensus on diagnosis, utilizing both a site based and centralized hematopathologist, with a third hematopathologist adjudicating diagnoses in cases of disagreement. This in and of itself has revealed clinically meaningful discrepancies in 25% of …