摘要
目的比较诱导化疗联合或不联合自体造血干细胞移植(auto-HSCT)治疗初治年轻弥漫大B细胞淋巴瘤(DLBCL)患者的疗效。方法回顾性分析90例年龄≤60岁、年龄调整的国际预后指数(aa-IPI)≥2分的初治DLBCL患者的临床资料,根据治疗方案将患者分为R-CHOP组(32例,利妥昔单抗联合CHOP方案化疗)、增强免疫化疗组(25例,利妥昔单抗联合EPOCH、Hyper-CVAD/R-MA或ESHAP方案化疗)和auto-HSCT组(33例,增强免疫化疗序贯auto-HSCT),进行疗效及相关预后因素分析。结果①90例患者中男40例(44.4%)、女50例(55.6%),中位年龄43(18~60)岁,中位随访时间42(3~110)个月。②R-CHOP组、增强免疫化疗组、auto-HSCT组5年无进展生存(PFS)率分别为(33.5±10.7)%、(55.3±10.1)%、(65.8±13.6)%(P=0.012),5年总生存(OS)率分别为(49.7±9.0)%、(61.6±10.2)%、(78.6±7.8)%(P=0.035)。R-CHOP组与增强免疫化疗组比较,5年PFS、OS率差异均无统计学意义(P=0.519,P=0.437);auto-HSCT组5年PFS率高于增强免疫化疗组(P=0.042)。③auto-HSCT组IPI分层高危患者(26例)、R-CHOP组低危患者(12例)、增强免疫化疗组低危患者(8例)的5年PFS率分别为(62.3±14.3)%、(58.3±18.6)%、(51.4±18.7)%(P=0.686),5年OS率分别为(69.2±13.9)%、(62.5±15.5)%、(58.3±18.6)%(P=0.592)。④高危患者比较,auto-HSCT组(26例)较R-CHOP组(20例)、增强免疫化疗组(17例)有更高的5年PFS率[(62.3±14.3)%、(41.1±13.5)%、(21.9±11.6)%,P=0.002]和5年OS率[(69.2±13.9)%、(51.5%±14.0)%、(35.4±13.6)%,P=0.019]。⑤R-CHOP组生发中心来源(GCB)亚型(16例)患者3年PFS、OS率均高于非生发中心来源(non-GCB)亚型患者(16例)(P=0.030,P=0.041);增强免疫化疗组GCB亚型患者(12例)3年PFS、OS亦高于non-GCB亚型患者(13例)(P=0.044,P=0.047);auto-HSCT组GCB亚型(15例)、non-GCB亚型患者(18例)3年PFS、OS率差异均无统计学意义(P=0.199,P=0.093)。⑥多因素结果分析显示,细胞来源(GCB/non-GCB)是影响R-CHOP组[PFS:HR=0.274(95% CI 0.094~0.800),P=0.018;OS:HR=0.408(95% CI 0.164~1.015),P=0.045]和增强免疫化疗组[PFS:HR=0.423(95% CI 0.043~1.152),P=0.048;OS:HR=5.758(95%CI 0.882~6.592),P=0.035]PFS率、OS率的独立预后因素,但不是影响auto-HSCT组PFS率、OS率的独立预后因素。结论增强免疫化疗序贯auto-HSCT可改善年轻初治高危DLBCL患者(特别是non-GCB亚型)的预后。
Objective To compare the efficacy of induction chemotherapy with or without autologous hematopoietic stem cell transplantation (auto-HSCT) for newly diagnosed young diffuse large B cell lymphoma (DLBCL) patients. Methods The retrospective study was performed in 90 cases of young patients (≤60 years) with newly diagnosed DLBCL and an age-adjusted International Prognostic Index (aa-IPI) score of 2 or 3. All of them were treated with R-CHOP (32 cases, rituximab combined with CHOP), dose-intensive regimens (DA-EPOCH, Hyper CVAD/MA or ESHAP) combined with or without rituximab (25 cases), and consolidated with up-front auto-HSCT (33 cases), respectively. The efficacy and the potential predictors were evaluated. Results ①The median age of 90 patients was 43 (18-60) years old. The median follow-up time was 42 (3-110) months.②The 5-year progression-free survival (PFS) for R-CHOP group, dose-intensive chemotherapy group and auto-HSCT group were (33.5±10.7)%,(55.3±10.1)% and (65.8±13.6)%(P=0.012), the 5-year overall survival (OS) were (49.7±9.0)%,(61.6±10.2)% and (78.6±7.8)%(P=0.035), respectively. There was no significant difference in 5-years PFS and OS between the R-CHOP group and dose-intensive chemotherapy group (P=0.519, P=0.437) compared with that of the dose-intensive chemotherapy group, auto-HSCT group has higher 5-year PFS (P=0.042).③ When stratified with IPI score, the high-risk group treated with auto-HSCT (26 cases) showed similar 5-years PFS and 5-years OS to those in the low-risk group with chemotherapy alone (12 cases were in R-CHOP group and 8 cases were in dose-intensive chemotherapy group)[5-years PFS were (62.3 ±14.3)%,(58.3 ±18.6)% and (51.4±18.7)%, respectively, P=0.686;5-years OS were (69.2±13.9)%,(62.5±15.5)% and (58.3±18.6)%, respectively, P=0.592].④However, the high-risk group treated with auto-HSCT (26 cases) showed superior 5-years PFS (P=0.002) and 5-years OS (P=0.019) compared to the high-risk group with chemotherapy alone (20 cases were in R-CHOP group and 17 cases were in dose-intensive chemotherapy group)[5-years PFS were (62.3±14.3)%,(41.1±13.5)% and (21.9±11.6)%, respectively;5-years OS were (69.2±13.9)%,(51.5%±14.0)% and (35.4±13.6)%, respectively].⑤In the univariate analysis, as a whole, patients diagnosed with GCB subtype had higher 3-years PFS (P=0.022) and 3-years OS (P=0.037) compared to non-GCB subtype patients;in subgroup analysis, patients diagnosed with GCB subtype had higher 3-years PFS and 3-years OS compared to non-GCB subtype both in R-CHOP group (P=0.030, P=0.041) and dose-intensive chemotherapy group (P=0.044, P=0.047), but not in auto-HSCT group (P=0.199, P=0.093).⑥In the multivariate analysis, different molecular classification (GCB/non-GCB) was an independent predictor for PFS and OS both in R-CHOP group [HR=0.274 (95% CI 0.094-0.800), P=0.018;HR=0.408 (95% CI 0.164-1.015), P=0.045] and dose-intensive chemotherapy group [HR=0.423 (95% CI 0.043-1.152), P=0.048;HR=5.758 (95% CI 0.882-6.592), P=0.035]. However, there was no significant difference in PFS and OS for auto-HSCT group between GCB/non-GCB patients. Conclusion Induction chemotherapy followed by up-front auto-HSCT has significant effect on efficacy for young and untreated patients with high risk DLBCL. Combined with induction chemotherapy followed by up-front auto-HSCT could improve the prognosis of non-GCB patients.
作者
王希
夏冰
王超雨
李梦真
许雯
袁田
田晨
赵海丰
杨洪亮
赵智刚
王晓芳
王亚非
于泳
张翼鷟
Wang Xi;Xia Bing;Wang Chaoyu;Li Mengzhen;Xu Wen;Yuan Tian;Tian Chen;Zhao Haifeng;Yang Hongliang;Zhao Zhigang;Wang Xiaofang;Wang Yafei;Yu Yong;Zhang Yizhuo(Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaXia Bing)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2019年第2期117-124,共8页
Chinese Journal of Hematology
基金
国家自然科学基金(81600163、81570201).
关键词
淋巴瘤
大B细胞
弥漫性
强力化疗
造血干细胞移植
Lymphoma, large B-cell, diffuse
Consolidation chemotherapy
Hematopoietic stem cell transplantation