R—CHOP方案治疗弥漫大B细胞淋巴瘤的预后因素分析

Prognostic factors analysis for R-CHOP regimen therapy in diffuse large B cell lymphoma

目的重新评估R—CHOP（利妥昔单抗、环磷酰胺、阿霉素、长春新碱、泼尼松）方案治疗弥漫大B细胞淋巴瘤（DLBCL）的预后因素。方法2000年2月至2006年9月125例初治DLBCL患者接受6个疗程的R—CHOP[利妥昔单抗375mg／m^2，缓慢静脉滴注，第1d；环磷酰胺750mg／m^2，静脉推注，第2d，阿霉素50mg／m^2，静脉推注，第2d；长春新碱1．4mg／m^2（最大剂量2．0mg），静脉推注，第2d，泼尼松60mg，口服，第2～6d]治疗后，对患者进行治疗反应的评估和随访。结果在入选的125例患者中，86例（68．8％）获得完全缓解（CR），16例（12．8％）获得部分缓解（PR），总反应率为81．6％，11例患者（8．8％）获得疾病稳定（SD），12例患者（9．6％）疾病进展。在单因素分析中，ECOG分级、临床分期、LDH水平、结外病变、国际预后指数（IPI）积分和巨块病变的有无均与CR有关；在多因素分析中，仅ECOG评分、临床分期和巨块病变对获得CR的差异有统计学意义（P值分别为0．0098、0．0000和0．0040）。患者24个月的治疗至失败时间（TTF）、总生存（OS）率和无病生存（DFS）率分别为（59．7±5．3）％、（67．1±5．6）％和（77．6±5．8）％。在单因素分析中，年龄和结外病变对TTF、OS和DFS率均无显著影响。而其余IPI因素，包括LDH、临床分期和行为状态对OS率和TTF均有显著影响，而对DFS率无明显影响。在多因素分析中，是否获得CR是影响TTF唯一的预后因素（P=0．001），它同时影响OS率（P=0．001）。其他影响OS率的指标包括LDH水平和ECOG评分（P值分别为0．002和0．009）。巨块病变是影响DFS率的唯一重要因素（P=0．007）。结论R—CHOP方案治疗中，IPI预后积分的预后意义具有一定局限性。6个疗程治疗后获得CR和巨块病变可能是IPI外另两个非常重要的临床预后因素。

Objective To reassess the prognostic factors of diffuse large B cell lymphoma （DLBCL） treated with R-CHOP therapy. Methods One hundred and twenty five patients were enrolled in this study from Feb. 2000 to Sep. 2006. They received 6 courses of R-CHOP regimen consisting of rituximab 375 mg/ m^2 , intravenously, d 1 ; cyclophosphamide 750 mg,/m^2 , bolus intravenously, d 2; doxorubicin 50 mg,/m^2 , bolus intravenously, d 2; vincristine 1.4 mg/m^2, bolus intravenously, d 2 and prednisone 60 mg, orally, d 2- 6. All the patients were evaluated and followed up after the treatment. Results Eighty six patients （68.8%） achieved complete response （ CR）, 16 （ 12.8% ） partial response （PR） , 11 （ 12.8% ） stable disease（SD） and 12 （9.6%） progressive disease （PD）. In univariate analysis, performance status （PS） , clinical stage, LDH level, extranodal disease, international prognostic index （IPI） and bulky disease were statistically significantly correlated with the induction of CR; however, only PS, clinical stage and bulky disease remained significant in multi-variate analysis （ P = 0. 0098, 0. 000 and 0. 004, respectively ）. Twenty four month for time to treatment failure （TTF） rate, overall survival （OS） rate, and disease free survival （DFS） rate was （59.7 ± 5.3）% , （67.1 ±5.6）% and （77.6 ± 5.8）%, respectively. In univariate analysis, LDH, clinical stage and PS exerted significant effect on TTF and OS rate, but not on DFS rate; age and extranodal disease was not related with TTF, OS and DFS rate. In multi-variate analysis, achieved CR was the only prognostic factor for TTF （P =0. 001 ） and bulky disease had influence on DFS rate. LDH level, PS,and achieved CR was correlated with the OS rate in muhi-variate setting （ P = 0.002, 0. 009 and 0.001 respectively）. Conclusion IPI score has its limitation in predicting the prognosis in the R-CHOP era in DLBCL. Other two relevant prognostic factors are bulky disease and achieved CR after 6 courses of treatment.