Seki Ritsuko, Ohshima Koichi, Fujisaki Tomoaki, Uike Naokuni, Kawano Fumio, Gondo Hisashi, Makino Shigeyoshi, Eto Tetsuya, Moriuchi Yukiyoshi, Taguchi Fumihiro, Kamimura Tomohiko, Tsuda Hiroyuki, Ogawa Ryosuke, Shimoda Kazuya, Yamashita Kiyoshi, Suzuki Keiko, Suzushima Hitoshi, Tsukazaki Kunihiro, Higuchi Masakazu, Utsunomiya Atae, Iwahashi Masahiro, Imamura Yutaka, Tamura Kazuo, Suzumiya Junji, Yoshida Minoru, Abe Yasunobu, Matsumoto Tadashi, Okamura Takashi
Division of Hematology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Cancer Sci. 2009 Oct;100(10):1842-7. doi: 10.1111/j.1349-7006.2009.01268.x. Epub 2009 Jul 1.
We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) +/- rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl-6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 (P = 0.001) or MUM1 (P = 0.011), or non-GCB subtype (P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R-CHOP group (P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated.
我们评估了在日本接受环磷酰胺、长春新碱、多柔比星和泼尼松（CHOP）±利妥昔单抗（R-CHOP）治疗的弥漫性大B细胞淋巴瘤（DLBCL）患者中预后标志物的效用。我们研究了730例DLBCL患者；451例接受CHOP治疗，279例接受R-CHOP治疗。我们对活检样本进行免疫组织化学分析，检测生发中心B细胞标志物（CD10、Bcl-6）、生发中心后B细胞标志物（多发性骨髓瘤-1）和凋亡标志物（Bcl-2）。存活患者的中位随访期，CHOP组为56.4个月，R-CHOP组为25.2个月。DLBCL被分为生发中心B（GCB）亚型（352/730；48.2%）或非生发中心B（non-GCB）亚型（378/730；51.8%）。在CHOP组中，CD10高表达（P = 0.022）或Bcl-6高表达（P = 0.021），或GCB亚型（P = 0.05）与较好的总生存期相关，而Bcl-2高表达（P = 0.001）或MUM1高表达（P = 0.011），或non-GCB亚型（P = 0.05）与较差的总生存期相关。然而，在R-CHOP组中，除Bcl-6外，这些生物标志物均不是显著的预后因素。non-GCB亚型患者在R-CHOP组中的生存期有所改善（P = 0.756）。国际预后指数是CHOP组（P < 0.001）和R-CHOP组（P < 0.001）中有用的生存临床标志物。添加利妥昔单抗后生存期改善的结果表明，应重新评估先前公认的预后因素的相关性。
