Negative impact of concurrent overexpression of MYC and BCL2 in patients with advanced diffuse large B-cell lymphoma treated with dose-intensified immunochemotherapy

• Published in: Leukemia & lymphoma 2016-12, Vol.57 (12), p.2784-2790
• Main Authors: Takahashi, Hiromichi, Miura, Katsuhiro, Nakagawa, Masaru, Sugitani, Masahiko, Amano, Yusuke, Kurita, Daisuke, Sakagami, Masashi, Ohtake, Shimon, Uchino, Yoshihito, Kodaira, Hitomi, Iriyama, Noriyoshi, Kobayashi, Sumiko, Hojo, Atsuko, Kobayashi, Yujin, Hirabayashi, Yukio, Kusuda, Machiko, Hatta, Yoshihiro, Nakayama, Tomohiro, Takei, Masami
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; BCL2; Biomarkers, Tumor; diffuse large B-cell lymphoma; double-expressor lymphoma; Female; Follow-Up Studies; Gene Expression; high-dose chemotherapy; Humans; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; MYC; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Survival Analysis; Treatment Outcome; Young Adult
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2016.1167205

Co-expression of MYC and BCL2 proteins in diffuse large B-cell lymphoma (DLBCL), or 'double-expressor lymphoma' (DEL), results in poor patient prognosis, but the significance of DEL when aggressive treatments are applied remains uncertain. We performed a retrospective analysis of 40 patients with de novo DLBCL, who were categorized as being at high/high-intermediate risk according to the age-adjusted International Prognostic Index. Patients underwent an R-Double-CHOP regimen, a dose-intensified immunochemotherapy with or without consolidative high-dose chemotherapy followed by autologous stem cell transplantation. According to immunohistochemical analysis, 10 (25%) patients were categorized as having DEL, showing positivity for MYC (≥40%) and BCL2 (≥50%). The 3 year progression-free survival and overall survival of the DEL group were significantly worse compared with those of the non-DEL group (30% vs. 63%, p = 0.019 and 40% vs. 82%, p = 0.006, respectively). These results suggest that advanced DEL may need discrete treatment strategies.