年轻高危弥漫大B细胞淋巴瘤患者的临床特征及疗效分析

Analysis of survival and treatment outcome of young patients with high-risk diffuse large B cell lymphoma

目的探讨年轻高危弥漫大B细胞淋巴瘤（DLBCL）患者的临床特征及疗效。方法回顾性分析2000年1月至2015年4月，在北京大学第三医院血液科就诊的122例年轻高危DLBCL患者的临床资料，对患者临床特征及实验室指标进行分析，同时进行生存和预后因素分析。结果年轻高危DLBCL占本中心DLBCL的发生率为27．1％，患者中位年龄44．0岁，Ⅲ、Ⅳ期患者占99．2％，50．0％患者存在两个及以上的淋巴结外器官受累；63．1％患者增殖指数Ki-67≥80％，30例患者行免疫组化检查显示双重表达患者占36．7％。初始治疗总有效率为79．4％，完全缓解率为39．7％，3和5年无进展生存分别为59．8％和57．0％；3和5年总生存率分别63．5％和57．8％，复发难治患者占44．3％。联合利妥昔单抗治疗组3年总生存率显著高于未联合利妥昔单抗治疗组（75．2％比46．1％，P=0．001）；初始强化治疗方案3年总生存率优于环磷酰胺、阿霉素、长春新碱联合泼尼松（CHOP方案）治疗组（84．6％比54．1％，P=0．006）；与化疗组比较，自体造血干细胞移植可进一步改善患者预后，3年总生存率分别93．4％比48．3％（P〈0．001）。单因素预后分析显示Ki-67水平、B症状、ECOG体能状态评分、血清乳酸脱氢酶水平、白细胞水平、白蛋白水平、红细胞沉降率水平、贫血、利妥昔单抗使用、初始治疗方案及是否联合自体造血干细胞移植、近期疗效和是否为复发难治状态与预后相关，多因素分析白蛋白水平（RR=5．462，P=0．019）、近期疗效（RR=34．863，P〈0．001）及是否为复发难治状态（RR=24．374，P〈0．001）为预后独立相关因素。结论年轻高危DLBCL在临床生物学行为及病理因素方面均表现为高度的侵袭性，利妥昔单抗的应用及高剂量化疗，能够改善患者生存，化疗联合自体造血干细胞移植可进一步改善患者预后。

Objective To analyze clinical feature and treatment outcome of young patients with high-risk diffuse large B cell lymphoma. Methods A total of 122 young patients with high-risk diffuse large B cell lymphoma who were treated in Third Hospital of Peking University during the period from January 2000 to April 2015 were retrospectively analyzed, and the clinical features, laboratory data were included in Kaplan-Meier and prognostic analysis. Results In our center, the incidence of young high-risk DLBCL was 27. 1% in all DLBCL patients, median age was 44. 0 years, 99. 2% patients belong to Ⅲ and Ⅳ stage, 50% patients had more than two extranodal organs involvement, and the higher proliferation index （Ki-67 ≥80% ） was present in 63.1% of patients, Immunohistochemistry showed that 36. 7% patients in 30 cases were double-expressed DLBCL. The overall response rate（ORR） for the whole group was 79. 4% ,the complete response rate was 39.7% ,the 3,5-year progression free survival rate was 59. 8% and 57. 0%, the 3,5-year overall survival rate was 63.5% and 57. 8%, respectively. 44. 3% patients were refractory-relapsed DLBCL. Rituximab can improve the survival of patients and 3-year overall survival rate was 75.2% vs 46. 1% （P =0. 001 ）. High-dose chemotherapy was superior to CHOP regimen which 3-year overall survival rate was 84. 6% vs 54. 1% （P = 0. 006）. Compared with chemotherapy group , auto-hematopoietic stem cell transplantation can improve prognosis of patients and 3-year overall survival rate was 93.4% vs 48.3% （P 〈 0. 001）. The level of Ki-67,B symptom, ECOG seore, the level of LDH, WBC and albumin, ESR level, anemia, rituximab therapy, initial regimens, ASCT, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated that albumin level （RR = 5. 462, P =0. 019 ）, initial treatment outcome （ RR = 34. 863, P 〈 0. 001 ） and refractory-relapsed （ RR = 24. 374, P 〈 0. 001 ） were independent prognostic risk factors. Conclusions Young patients with high-risk DLBCL were highly aggressive in clinical and pathological features. Rituximab and high-dose regimens can improve the survival of patients.