本帖最后由 橙色雨丝 于 2016-12-15 11:04 编辑
High Risk Diffuse Large B Cell Lymphoma: A Comparison of Aggressive Subtypes Treated with Dose Adjusted Chemotherapy—the University of Texas MD Anderson Experience 高风险弥漫大B淋巴瘤：MD Anderson用剂量调整方案治疗高侵袭性亚型的经验
Background: Diffuse large B celllymphoma (DLBCL) is the most common type of non Hodgkin lymphoma(NHL). Nearly 50% of high-risk DLBCL patients are not cured with standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP).High risk DLBCL may be defined as double hit lymphoma (DHL, translocation ofMYC and BCL2 or BCL6), double expressor lymphoma (DEL, over expression of MYCand BCL2), high risk international prognostic index (IPI) of 3-5, high Ki-67,and non-germinal center subtype (non-GCB). The majority of DHL cases occur in the GCB subtype, as opposed to the majority of DEL cases which occur innon-GCB. Hence we sought to compare different high risk subsets treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and rituximab (DA) EPOCH-R. In single arm phase II clinical trials, dose adjusted (DA) EPOCH-R has shown promising results, with potential greater efficacy in the GCB subtype in subset analyses (Wilson et al, Hematologica2012). A randomized phase III study comparing RCHOP with (DA) EPOCH-R in newly diagnosed DLBCL has completed accrual, with highly anticipated results due inlate 2016. 背景：弥漫大B细胞淋巴瘤是非霍奇金淋巴瘤当中最常见的类型。大约有50%的高风险的弥漫大B不能用标准的RCHOP方案（利妥昔单抗，环磷酰胺，多柔比星，长春新碱和泼尼松）治愈。高风险弥漫大B可以定义为双重打击淋巴瘤（DHL，MYC、BCL2或BCL6易位），双重表达淋巴瘤（DEL，MYC和BCL2过表达），国际预后指数3-5，高Ki67值，和非生发中心亚型（non-GCB）。大部分双重打击发生于GCB亚型，而大部分双重表达发生于non-GCB亚型。这里我们来比较不同的高风险亚组用DA-EPOCH-R方案（剂量调整的依托泊苷，多柔比星，环磷酰胺，长春新碱，泼尼松和利妥昔单抗）治疗的效果。在单臂II期临床试验中，DA-EPOCH-R显示出很好效果，亚组分析表明最大有效率可能发生在GCB亚组中。一项针对初治患者比较R-CHOP和DA-EPOCH-R方案的III期随机临床试验已经完成入组，2016年末会公布非常令人期待的结果。
Methods: We conducted a retrospective review of all consecutive, newly diagnosed DLBCL patients treated with (DA)EPOCH-R at MD Anderson Cancer Center from 2010 to 2014. Eligible patients were 18 years or greater, had high-risk DLBCL as determined by the treating physician, and had available data of treatment and response. The cell of origin subtype was determined by immunohistochemistry using Hans algorithm,and MYC and BCL2 positivity were defined as BCL2 positive in at least 70% and MYC positive in at least 40% of cells. DHL was defined as rearrangement of MYC and BCL2 or BCL6 by fluorescent in situ hybridization. The objectives were to analyze demographic, prognostic, and treatment variables in comparison with clinical response and survival outcomes in three sub groups which included 1.DHL (GCB) 2. DLBCL without MYC and BCL2 expression (GCB), and 3. DEL (GCB andnon GCB). Complete response (CR), overall survival (OS) and progression free survival (PFS) were calculated using standard methods. Statistical analysis wasdone using Fishers exact test or Chi-square test / Kruskal-Wallis test.Kaplan-Meier method was used for time-to-event analysis including overall survival and progression free survival. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. 方法：我们开展了一项回顾性研究，研究对象是从2010年到2014年所有在MD Anderson接受DA-EPOCH-R方案治疗的弥漫大B患者。选择条件包括18岁以上，主治医生判定为高风险，有治疗和随访的数据。细胞来源的亚型通过免疫组化根据Hans公式确定，MYC阳性和BCL2阳性分别定义为40%和70%的细胞呈阳性。双重打击定义为FISH发现MYC，BCL2或BCL6重排。研究目的是分析三个亚组在统计学、预后和治疗中的变量与临床效果和生存数据的比较，三个亚组分别为：1. 双重打击（GCB）；2. 没有MYC和BCL2表达的弥漫大B（GCB）3. 双重表达（GCB和non-GCB）。（以下省略）
Results: We identified 233 high risk DLBCL patients treated with (DA) EPOCH-R. After filtering the data to identify patients which were included in our three groups, we identified 22 patients with DHL (GCB), 46 patients with non DEL (GCB), and 16 with DEL. The demographic features and outcomes are mentioned in the table 1 below. The DHL group had more frequent bone marrow (BM) involvement, and the DHL and DEL groups were more frequently age >60 years and high IPI in comparison to the non DEL GCB group. The CR rate, OS and PFS at 1 year were not significantly different between these three groups. Figure 1 highlights the OS (A) and PFS(B) results of each group. 结果：我们找出了233位接受DA-EPOCH-R治疗的高危弥漫大B患者。经过数据过滤，我们确定了22位双重打击（GCB），46位非双重表达（GCB）和16位双重表达。统计学数据和结果见表1.双重打击组有较多的骨髓侵犯，双重打击组和双重表达组年龄普遍大于60岁，IPI与非双重表达（GCB）组更高。三个亚组1年的完全缓解率，总生存率和无进展生存率没有明显区别。
Conclusions: (DA) EPOCH-R is highly effective in patients with subsets of patients with high-risk DLBCL and may be able to overcome prognostic factors which have been shown to be adverse with RCHOP therapy. The results of this retrospective study suggest that OS in DHL,DEL and non DEL (GCB) are not statistically different. Hence, intensive chemotherapy with (DA) EPOCH-R could be considered as a frontline treatment option for patients with high risk DLBCL, pending further confirmation in randomized trials. 结论：DA-EPOCH-R对高风险弥漫大B非常有效，或者可以克服用RCHOP方案无法克服的不良预后因素。这项回顾性研究的结果提示，双重打击，双重表达和非双重表达（GCB）弥漫大B在总生存率上没有统计学上的差异。因此，DA-EPOCH-R强化方案可以考虑作为高风险弥漫大B一线治疗的可选方案，适用性有待随机临床试验的验证。
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