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.
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。.
Keywords: Consolidation chemotherapy; Hematopoietic stem cell transplantation; Lymphoma, large B-cell, diffuse.