Savage K J, Al-Rajhi N, Voss N, Paltiel C, Klasa R, Gascoyne R D, Connors J M
University of British Columbia and the British Columbia Cancer Agency, Vancouver, BC, Canada.
Ann Oncol. 2006 Jan;17(1):123-30. doi: 10.1093/annonc/mdj030. Epub 2005 Oct 19.
Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinico-pathological subtype of diffuse large B-cell lymphoma (DLBCL). The optimal treatment is unknown, with some studies suggesting a superior outcome with dose-intensive chemotherapy regimens, and the role of radiotherapy remains ill-defined.
The British Columbia Cancer Agency lymphoma database was searched and records reviewed to identify those patients presenting with a prominent mediastinal mass and considered to be PMBCL based on the current REAL/WHO classifications. Patients were treated based on era-specific BCCA guidelines (1980-1992 MACOPB/VACOPB; 1992-2001 CHOP-type; 2001-present CHOP-R). Beginning in January 1998 involved-field radiotherapy was recommended to be routinely administered following chemotherapy. Prior to this, use of radiotherapy was individualized in advanced disease.
In total, 153 patients with newly diagnosed PMBCL were identified between 28 July 1980 and 30 June 2003. The median age was 37 years (range 13-82) and the majority had stage I/II (74%), bulky mediastinal disease (75%). Overall (OS) and progression-free (PFS) survival at 5 years for the entire cohort were 75% and 69%, respectively. In direct comparison with a cohort of patients with DLBCL (n = 1273), OS (P = 10(-4)) and PFS (P = 0.0001) favored PMBCL. The age-adjusted International Prognostic Index (aaIPI) was not predictive of survival (P = 0.18). Five-year OS in patients < 65 years old treated with MACOPB/VACOPB, CHOP-R and CHOP-type was 87%, 81% and 71% respectively (P = 0.048). In pair-wise survival comparisons, only MACOPB/VACOPB and CHOP-type treated patients were significantly different (P = 0.016). In Cox multiple regression analysis, poor performance status remained the only predictor of survival, with treatment received demonstrating a trend to worse outcome for patients treated with CHOP-type regimens (P = 0.09). In an intention-to-treat analysis comparing the era before radiotherapy was routinely administered with after, there was no significant difference in 5-year PFS (74% versus 62%; P = 0.09) or OS (78% versus 69%; P = 0.14).
In this single institution, population-based retrospective study, we found that PMBCL patients have excellent survival rates and a distinct plateau is observed in PFS, in striking comparison to DLBCL. The aaIPI was not predictive of survival in this population, suggesting that other prognostic models may be better suited for risk stratification. Dose-intensified chemotherapy with MACOPB or VACOPB demonstrated a trend to superior outcome over CHOP-type chemotherapy. However, further randomized studies are needed and the impact of rituximab on these comparisons must be considered. Finally, the routine addition of radiotherapy does not improve survival.
原发性纵隔大B细胞淋巴瘤（PMBCL）是弥漫性大B细胞淋巴瘤（DLBCL）一种独特的临床病理亚型。最佳治疗方案尚不清楚，一些研究表明剂量密集化疗方案疗效更佳，而放疗的作用仍不明确。
检索不列颠哥伦比亚癌症机构淋巴瘤数据库并审查记录，以确定那些出现明显纵隔肿块且根据当前REAL/WHO分类被认为是PMBCL的患者。患者根据特定时期的BCCA指南进行治疗（1980 - 1992年采用MACOPB/VACOPB方案；1992 - 2001年采用CHOP类方案；2001年至今采用CHOP - R方案）。从1998年1月起，建议在化疗后常规进行累及野放疗。在此之前，晚期疾病患者的放疗使用是个体化的。
1980年7月28日至2003年6月30日期间共确定了153例新诊断的PMBCL患者。中位年龄为37岁（范围13 - 82岁），大多数患者为Ⅰ/Ⅱ期（74%），有巨大纵隔病变（75%）。整个队列的5年总生存率（OS）和无进展生存率（PFS）分别为75%和69%。与一组DLBCL患者（n = 1273）直接比较，PMBCL的OS（P = 10⁻⁴）和PFS（P = 0.0001）更优。年龄调整后的国际预后指数（aaIPI）不能预测生存率（P = 0.18）。接受MACOPB/VACOPB、CHOP - R和CHOP类方案治疗的＜65岁患者的5年OS分别为87%、81%和71%（P = 0.048）。在成对生存比较中，仅接受MACOPB/VACOPB和CHOP类方案治疗的患者有显著差异（P = 0.016）。在Cox多因素回归分析中，体能状态差仍然是生存的唯一预测因素，接受CHOP类方案治疗的患者的治疗结果有更差的趋势（P = 0.09）。在一项意向性分析中，比较放疗常规应用前后的时期，5年PFS（74%对62%；P = 0.09）或OS（78%对69%；P = 0.14）无显著差异。
在这项单机构、基于人群的回顾性研究中，我们发现PMBCL患者生存率极佳，PFS出现明显平台期，这与DLBCL形成鲜明对比。aaIPI不能预测该人群的生存率，表明其他预后模型可能更适合风险分层。与CHOP类化疗相比，采用MACOPB或VACOPB的剂量强化化疗有疗效更优的趋势。然而，需要进一步的随机研究，并且必须考虑利妥昔单抗对这些比较的影响。最后，常规加用放疗并不能提高生存率。
