van Imhoff Gustaaf W, Boerma Evert-Jan G, van der Holt Bronno, Schuuring Ed, Verdonck Leo F, Kluin-Nelemans Hanneke C, Kluin Philip M
Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Clin Oncol. 2006 Sep 1;24(25):4135-42. doi: 10.1200/JCO.2006.05.5897.
Outcome of diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) expression profile is superior to that of non-GCB DLBCL. This conclusion is mainly derived from patients with mixed international prognostic index (IPI) risk profiles treated with CHOP-like therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). We wondered whether the prognostic impact of the expression profile would hold out in a homogeneous cohort of poor-risk DLBCL patients treated with high-dose sequential therapy (HDT) and autologous stem-cell transplantation (ASCT) as first-line therapy.
DLBCL from 66 newly diagnosed poor-risk patients, treated in two sequential prospective Dutch Hemato-Oncology Association (HOVON) trials, were studied retrospectively for expression of CD10, bcl6, MUM1/IRF4, bcl2, Ki67, and CD21+ follicular dendritic cells (FDC) by immunohistochemistry, and for the breakpoints of BCL2, BCL6, and MYC by fluorescent in situ hybridization (FISH). Lymphomas with any follicular component were excluded.
A GCB immunophenotype profile was found in 58% and non-GCB immunophenotype profile in 42% of the tumors. Clinical characteristics of both groups were similar. Complete response (CR) rate was higher in patients with CD10+ tumors (58% v 30%; P = .03). A GCB immunophenotype profile, its constituting markers CD10 more than 30% and MUM1 less than 70%, and bcl2 less than 10% were each associated with a better overall survival (OS). FDC networks, equally present in GCB and non-GCB tumors, had superior CR (73% v 31%; P = .01), but disease-free survival rates were lower and there was no difference in OS rates. None of the breakpoints had a prognostic impact on outcome.
Also in patients with poor-risk DLBCL treated with HDT and ASCT, the GCB immunophenotype and bcl2 expression retained a major impact on survival.
具有生发中心B细胞（GCB）表达谱的弥漫性大B细胞淋巴瘤（DLBCL）的预后优于非GCB DLBCL。这一结论主要源于接受CHOP样治疗（环磷酰胺、阿霉素、长春新碱和泼尼松）的具有混合国际预后指数（IPI）风险谱的患者。我们想知道，在作为一线治疗接受大剂量序贯治疗（HDT）和自体干细胞移植（ASCT）的高危DLBCL患者的同质队列中，表达谱的预后影响是否依然存在。
对在两项荷兰血液肿瘤协会（HOVON）前瞻性序贯试验中接受治疗的66例新诊断高危患者的DLBCL进行回顾性研究，通过免疫组织化学检测CD10、bcl6、MUM1/IRF4、bcl2、Ki67和CD21+滤泡树突状细胞（FDC）的表达，并通过荧光原位杂交（FISH）检测BCL2、BCL6和MYC的断点。排除任何具有滤泡成分的淋巴瘤。
58%的肿瘤具有GCB免疫表型谱，42%具有非GCB免疫表型谱。两组的临床特征相似。CD10+肿瘤患者的完全缓解（CR）率更高（58%对30%；P = 0.03）。GCB免疫表型谱、其构成标志物CD10超过30%且MUM1低于70%以及bcl2低于10%均与更好的总生存期（OS）相关。FDC网络在GCB和非GCB肿瘤中均同样存在，其CR更高（73%对31%；P = 0.01），但无病生存率较低，OS率无差异。没有一个断点对预后有影响。
在接受HDT和ASCT治疗的高危DLBCL患者中，GCB免疫表型和bcl2表达对生存仍有主要影响。
