利妥昔单抗联合自体外周血干细胞移植治疗弥漫大B细胞淋巴瘤的疗效观察

Combination of rituximab with autologous peripheral blood stem cell transplantation for treatment of diffuse large B-cell lymphoma： a single-center experience

目的探讨利妥昔单克隆抗体（单抗）联合自体外周血干细胞移植治疗弥漫大B细胞淋巴瘤（DLBCL）的疗效及影响预后的因素。方法回顾性分析25例接受利妥昔单抗体内净化联合自体外周血干细胞移植治疗的DLBCL患者临床资料。患者中位年龄39（17—61）岁，AnnArborI一Ⅱ期2例、Ⅲ期3例、Ⅳ期20例，60％患者有B组症状，国际预后指数（IPI）评分低危组、低中危组、高中危组及高危组患者分别为2、11、10及2例。预处理方案采用BEAM方案（21例）及全身照射为主的方案（4例）。造血干细胞动员化疗前1d及化疗后第7天、自体造血干细胞回输前1d及回输后第8天各输注利妥昔单抗1次，每次剂量为375mg／m2。结果自体造血干细胞移植前疾病获得完全缓解（CR）者20例、部分缓解者5例。92％患者于移植后达到CR。中位随访时间45（2～121）个月，19例无病存活，4例死亡。全组患者3年总生存率及无进展生存（PFS）率分别为78．9％及75．9％，累积复发及进展率为19．1％。20例移植前CR的患者3年总生存率及PFS率分别为87．4％及82．4％，复发率为11．8％。多因素分析显示，移植前是否CR是影响总生存的独立危险因素，而IPI是影响PFS的独立危险因素。结论利妥昔单抗体内净化联合自体外周血干细胞移植治疗DLBCL的疗效良好。

Objective This study was aimed to investigate whether incorporation of rituximab into high-dose chemotherapy with autologous peripheral blood stem cell transplantation （auto-PBSCT） could im- prove the survival of patients with diffuse large B-cell lymphoma （ DLBCL）, and evaluate the safety of this regimen. Methods Twenty-five patients （age, 17 -61 yrs） with DLBCL were treated with a sequential chemotherapy for remission induction, intensive chemotherapy for mobilization of stem cells, and high-dose chemotherapy followed by auto-PBSCT. Among 25 patients, 22 eases were at IV Ann Arbor stage, 60% cases with B symptom, and 10 cases with intermediate-high risk and 2 cases with high risk when evaluated by Inter- national Prognostic Index （IPI）. The high-dose chemotherapy included BEAM regimen for 21 patients, and TBI conditioning regimen for 4 patients. Each patient received infusion of rituximab at a dose of 375 mg/m2 for 2 times, each at peripheral blood stem cell mobilization and peripheral stem cell infusion. Results 20 pa- tients achieved complete remission （CR） before transplantation. After high-dose chemotherapy and auto-PB- SCT, 92% patients achieved CR. At a median follow-up of 45 months, the estimated 3-year overall survival （OS） and progression-free survival （PFS） were 78.9% and 75.9%, respectively, for all patients; while those were 87.4% and 82.4% for patients achieved CR before auto-PBSCT. Multivariate analysis by Cox re- gression revealed that failure to achieving CR before auto-PBSCT was an independent prognostic factor affect- ing OS, while factor affecting PFS was IPI scores. Rituximab was generally well tolerated with few side-effects. Conclusion Our resuhs suggested that the addition of rituximab to high-dose chemotherapy followed by auto-PBSCT was effective and safe for patients with DLBCL.