诱导化疗联合或不联合自体造血干细胞移植治疗年龄≤60岁初治中高危/高危弥漫大B细胞淋巴瘤的比较研究

A comparative study of induction chemotherapy with or without autologous hematopoietic stem cell transplantation in the treatment of newly diagnosed young medium/high risk diffuse large B cell lymphoma patients

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.