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Expanding and expounding the genomic map of CTCL
Blood ( IF 20.3 ) Pub Date : 2017-09-21 , DOI: 10.1182/blood-2017-08-797399
Anjali Mishra 1 , Pierluigi Porcu 2
Affiliation  

Background: Acute myeloid leukemia (AML) is a highly heterogenous condition. Current risk stratification based on cytogenetics and molecular genetic markers at point of diagnosis is used to predict treatment response and relapse risk. The conventional way of defining complete remission (CR) is based on morphological identification of ≤5% blasts seen in bone marrow. However, this does not provide adequate insight to the quality of response as there is still a high proportion of patients that relapse despite being in CR. A significant proportion of AML patients have detectable MRD post induction. There is increasing evidence to support MRD as a significant prognostic factor for clinical outcome. Despite this, MRD status has yet to become an important factor in deciding on subsequent allogeneic stem cell transplant (allo-SCT). This study assessed the role MRD in predicting risk of relapse and survival rates and also looked into the role of allo-SCT in abrogating the adverse risk of MRD. Methods: All AML cases excluding acute promyelocytic leukemia who underwent curative chemotherapy from year 2001 until 2015 were retrospectively identified. Clinical data was gathered from computerized patient data system. Baseline patients and disease characteristic were correlated with post induction MRD status. MRD was assessed by flow cytometry analysis of bone marrow samples taken on day 26-30 days of post-induction. Samples from year 2001 to 2011 were analyzed using 4 color flow, and from 2011 onward, all samples were analyzed using 8 color flow. Leukemia-associated antigens were identified at baseline and followed up for MRD. Data collected were analyzed using SPSS Statistic Desktop V22.0. Results: 235 patients underwent intensive chemotherapy. 61.7% achieved complete remission (CR) after induction chemotherapy. Among those who achieved CR after induction, 41.3% have detectable MRD. 42.8% eventually relapsed, after a median follow-up of 36.6 months. Median duration of CR was 49.5 months. The presenting WBC, LDH, time taken for neutrophil count or platelet count recovery after induction, cytogenetic risk group and FLT3-ITD and NPM1 molecular status did not correlate with MRD status. Post induction MRD positive status was associated with higher relapse rate, 42.6% vs 22.4% for MRD positive and negative respectively, p=0.015, (OR = 1.9) (95% CI: 1.14-3.19). In the multivariate analysis that include presenting WBC, LDH, BM blasts, risk group and post induction MRD status, risk group and MRD status remained an independent predictor for relapse. HR 1.95 (95% CI: 1.00-3.79), p=0.049 for positive MRD status, while adverse risk group gave a HR of 7.15 (95%CI: 2.01-25.49), p=0.002. The 3-year Leukemia free survival (LFS) was 38.3% and 59.6% for MRD+ and MRD- group respectively (p=0.043) (figure 1), while the overall survival (OS) was 55.5% and 69.5% for MRD+ and MRD- group respectively (p=0.388). 55 patients underwent allo-SCT, 26 in MRD+ group and 29 in MRD- group. There was no statistical significance in terms of LFS among those who underwent allo-SCT according to MRD status (Median LFS were 13.1 months for MRD+, 29.2 months for MRD-, p=0.328). In the intermediate or adverse risk group who did not undergone allo-SCT, the median LFS in MRD+ group was only 2.5 months (95%CI: 0.0-21.2) compared to MRD- group, 39.9 months (p=0.041), (figure 2). Conclusions: Post induction MRD+ was associated with higher relapse rate and reduced LFS. Post induction MRD- status was associated with excellent LFS among AML with intermediate and adverse risk even without allo-SCT. Allo-SCT may be able to abrogate the adverse outcome of MRD+ AML. Disclosures No relevant conflicts of interest to declare.

中文翻译:

CTCL基因组图谱的拓展与阐述

背景:急性髓系白血病(AML)是一种高度异质性的疾病。在诊断时基于细胞遗传学和分子遗传标记的当前风险分层用于预测治疗反应和复发风险。定义完全缓解 (CR) 的传统方法是基于骨髓中≤5% 原始细胞的形态学鉴定。然而,这并不能提供对反应质量的充分了解,因为尽管处于 CR 状态,仍有很高比例的患者复发。很大比例的 AML 患者在诱导后具有可检测的 MRD。越来越多的证据支持 MRD 作为临床结果的重要预后因素。尽管如此,MRD 状态尚未成为决定后续同种异体干细胞移植 (allo-SCT) 的重要因素。本研究评估了 MRD 在预测复发风险和存活率方面的作用,并研究了 allo-SCT 在消除 MRD 不利风险方面的作用。方法:对2001年至2015年间接受根治性化疗的除急性早幼粒细胞白血病外的所有AML病例进行回顾性分析。临床数据是从计算机化的患者数据系统中收集的。基线患者和疾病特征与诱导后 MRD 状态相关。MRD 通过流式细胞术分析在诱导后第 26-30 天采集的骨髓样品进行评估。从 2001 年到 2011 年的样品使用 4 色流进行分析,从 2011 年开始,所有样品都使用 8 色流进行分析。在基线时确定白血病相关抗原并随访 MRD。使用 SPSS Statistic Desktop V22.0 分析收集的数据。结果:235例患者接受了强化化疗。61.7% 的患者在诱导化疗后达到完全缓解(CR)。在诱导后达到 CR 的患者中,41.3% 具有可检测到的 MRD。在中位随访 36.6 个月后,42.8% 的患者最终复发。CR 的中位持续时间为 49.5 个月。目前的 WBC、LDH、诱导后中性粒细胞计数或血小板计数恢复所需的时间、细胞遗传风险组和 FLT3-ITD 和 NPM1 分子状态与 MRD 状态无关。诱导后 MRD 阳性状态与较高的复发率相关,MRD 阳性和阴性分别为 42.6% 和 22.4%,p=0.015,(OR = 1.9)(95% CI:1.14-3.19)。在包括呈现 WBC、LDH、BM 原始细胞、风险组和诱导后 MRD 状态的多变量分析中,风险组和 MRD 状态仍然是复发的独立预测因素。HR 1.95(95% CI:1.00-3.79),阳性MRD状态p=0.049,而不利风险组的HR为7.15(95%CI:2.01-25.49),p=0.002。MRD+ 和 MRD- 组的 3 年无白血病生存率 (LFS) 分别为 38.3% 和 59.6% (p=0.043)(图 1),而 MRD+ 和 MRD 的总生存率 (OS) 分别为 55.5% 和 69.5% - 分别为组 (p=0.388)。55例患者接受allo-SCT,MRD+组26例,MRD-组29例。根据 MRD 状态,接受 allo-SCT 的患者的 LFS 没有统计学意义(MRD+ 的中位 LFS 为 13.1 个月,MRD- 为 29.2 个月,p=0.328)。在未接受 allo-SCT 的中等或不良风险组中,MRD+ 组的中位 LFS 仅为 2.5 个月(95%CI:0.0-21.2),而 MRD- 组为 39。9 个月 (p=0.041),(图 2)。结论:诱导后 MRD+ 与较高的复发率和降低的 LFS 相关。即使没有allo-SCT,诱导后MRD-状态与具有中等和不良风险的AML中的优异LFS相关。Allo-SCT 可能能够消除 MRD+ AML 的不良后果。披露 没有需要申报的相关利益冲突。
更新日期:2017-09-21
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