James P Wilmot Cancer Center and University of Rochester, Rochester, NY 14642, USA.
Hematology Am Soc Hematol Educ Program. 2011;2011:498-505. doi: 10.1182/asheducation-2011.1.498.
Despite overall improvements in outcomes of diffuse large B-cell lymphoma (DLBCL), approximately one-third of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality. Novel insights from gene-expression analyses have increased our understanding of chemotherapy resistance and yielded rational targets for therapeutic intervention to both prevent and treat relapsed/refractory DLBCL. The clinical approach to relapsed/refractory DLBCL should include high-dose therapy and autologous stem cell transplantation (HD-ASCT) with curative intent in patients without comorbidities. Results from the recently reported CORAL study suggest that patients refractory to rituximab-containing regimens have inferior outcomes with HD-ASCT. Ongoing efforts to improve ASCT include novel conditioning regimens and evaluation of maintenance approaches after ASCT. Unfortunately, because the majority of patients are not eligible for ASCT due to refractory disease or age/comorbidities, these approaches have limited impact. The large group of patients not eligible for ASCT have incurable disease and should be referred for clinical trials of rationally targeted agents.
尽管弥漫性大 B 细胞淋巴瘤（DLBCL）的总体治疗效果有所改善，但仍有约三分之一的患者会出现复发/难治性疾病，这仍然是发病率和死亡率的主要原因。基因表达分析的新见解增加了我们对化疗耐药性的理解，并为治疗干预提供了合理的靶点，以预防和治疗复发/难治性 DLBCL。对于无合并症的患者，复发/难治性 DLBCL 的临床治疗方法应包括大剂量化疗和自体造血干细胞移植（HD-ASCT），以期治愈。最近报告的 CORAL 研究的结果表明，对含利妥昔单抗方案耐药的患者在接受 HD-ASCT 后预后较差。目前正在努力改进 ASCT，包括新的预处理方案和评估 ASCT 后的维持方法。不幸的是，由于大多数患者因疾病复发或年龄/合并症而不适合 ASCT，这些方法的影响有限。大多数不适合 ASCT 的患者患有无法治愈的疾病，应被推荐参加合理靶向药物的临床试验。
