Yamamoto Masahide, Watanabe Ken, Fukuda Tetsuya, Miura Osamu
Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan
Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan.
Anticancer Res. 2017 May;37(5):2655-2662. doi: 10.21873/anticanres.11613.
Prognostic models for primary diffuse large B-cell lymphoma (DLBCL) resistant to or relapsing after initial therapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) have not been well-established. A refined categorization of normalized lactate dehydrogenase (LDH) (the ratio to the upper limit of normal) was recently shown to predict prognosis of newly-diagnosed patients with DLBCL better than mere dichotomization of LDH into 'normal' and 'abnormal' groups. To define the prognostic impact of the LDH ratio and various other factors in order to develop a new prognostic model system, we retrospectively analyzed 31 patients with refractory/relapsed DLBCL initially treated with R-CHOP at our hospital from 2002 to 2013. Median age at the start of salvage therapy was 63 years. Median time from diagnosis to relapse was 349 days. In univariate analysis, LDH, short time from initial diagnosis to relapse (TTR), and low absolute lymphocyte count at relapse (ALC-R) were significant factors for reduced progression-free survival, and the LDH ratio was a more powerful factor than LDH abnormality. Furthermore, an LDH ratio >3 and short TTR were independent prognostic factors in multivariate analysis. We built a new prognostic scoring system, namely the time, LDH, and lymphocyte count (TLL), based on TTR, LDH ratio, and ALC-R, which is able to separate patients into three risk groups with 2-year PFS of 100%, 68.6% and 4.8%, respectively, and which also predicts outcome of autologous stem cell transplantation at the start of salvage therapy. The present study indicates that the LDH ratio is an important predictor of survival for patients with refractory/relapsed DLBCL and proposes the TLL index as a useful prognostic tool.
对于接受利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松(R-CHOP)初始治疗后耐药或复发的原发性弥漫性大B细胞淋巴瘤(DLBCL),其预后模型尚未完全确立。最近研究表明,对标准化乳酸脱氢酶(LDH)(与正常上限的比值)进行细化分类,比单纯将LDH分为“正常”和“异常”两组,能更好地预测新诊断DLBCL患者的预后。为了确定LDH比值和其他各种因素的预后影响,从而开发一种新的预后模型系统,我们回顾性分析了2002年至2013年在我院接受R-CHOP初始治疗的31例难治性/复发性DLBCL患者。挽救治疗开始时的中位年龄为63岁。从诊断到复发的中位时间为349天。单因素分析中,LDH、从初始诊断到复发的时间短(TTR)以及复发时低绝对淋巴细胞计数(ALC-R)是无进展生存期缩短的显著因素,且LDH比值比LDH异常是更强有力的因素。此外,在多因素分析中,LDH比值>3和TTR短是独立的预后因素。我们基于TTR、LDH比值和ALC-R建立了一种新的预后评分系统,即时间、LDH和淋巴细胞计数(TLL),该系统能够将患者分为三个风险组,其2年无进展生存率分别为100%、68.6%和4.8%,并且还能在挽救治疗开始时预测自体干细胞移植的结果。本研究表明,LDH比值是难治性/复发性DLBCL患者生存的重要预测指标,并提出TLL指数作为一种有用的预后工具。