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利妥昔单抗联合强化免疫化疗治疗散发性成人伯基特淋巴瘤:疗效与预后分析

[Rituximab combined with intensive immunochemotherapy for sporadic adult Burkitt lymphoma: efficacy and prognosis analyse].

作者信息

Dong C M, Zou H S, Zhang W, Liu W, Wang Y, Liu H M, Xie T, Li H, Wang Q, Huang W Y, Yi S H, An G, Qiu L G, Zou D H

机构信息

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences &Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2025 Feb 14;46(2):134-139. doi: 10.3760/cma.j.cn121090-20241130-00505.

Abstract

To explore the therapeutic efficacy and prognostic factors of combined rituximab and intensive chemotherapy for sporadic adult Burkitt lymphoma (BL) . This retrospective study examined the clinical and survival data of 30 patients newly diagnosed with BL between July 2011 and February 2023 at the Blood Diseases Hospital. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of prognostic factors. The median age of the 30 patients was 43 years (24 - 66 years), and the male to female ratio was 3: 2. Extranodal invasion was present in 80% of the patients, with involvement of the bone marrow in 53.3% and central nervous system in 10.0%. The Ann Arbor stage was Ⅲ and Ⅳ in 86.7%. According to the number of Burkitt Lymphoma International Prognostic Index (BL-IPI) risk factors, patients were classified as low risk (0) in 20.0%, intermediate risk (1) in 43.3%, and high risk (≥2) in 36.7%. All patients were treated with an induction regimen of rituximab combined with intensive chemotherapy, with objective and complete response rates of 80.0% and 76.7%, respectively. The median follow-up was 49 months (6-153 months), and the 5-year progression-free survival (PFS) and overall survival (OS) rates were both (76.7±7.7) %. All patients with limited stage (=4) achieved continuous complete remission (CCR). Patients who had high risk, advanced stage sensitive to induction therapy (=10) sequentially received first-line autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy; 9 patients achieved CCR, whereas 1 patient with central nervous system invasion developed early disease progression and died. The BL-IPI low, intermediate, and high risk groups had respective 5-year PFS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % (=0.0069) and OS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % (=0.0075). The main adverse effects of induction therapy were myelosuppression and secondary infections, which were effectively managed by appropriate symptomatic treatment. Univariate analysis demonstrated that worse PFS was associated with BL-IPI score ≥2 (=4.90, 95% 1.02-23.45, =0.0329) ; extranodal invasion at ≥2 sites (=12.62, 95% 2.59-61.62, =0.0021) ; and failure to achieve first complete response (CR1) after induction therapy (=31.86, 95% 4.19-242.20, <0.0001) . Intensive immunochemotherapy regimens were effective and well-tolerated by adult patients with highly aggressive BL. Treatment efficacy was ideal in patients with limited-stage disease, whereas prognosis was unsatisfactory in patients with high-risk BL-IPI. Sequential first-line auto-HSCT consolidation therapy may further improve outcomes in patients with high-risk advanced-stage disease who are sensitive to induction therapy. BL-IPI score ≥2, extranodal invasion at ≥2 sites, and failure to achieve CR1 after induction therapy were adverse prognostic factors in adult patients with BL.

摘要

探讨利妥昔单抗联合强化化疗治疗散发性成人伯基特淋巴瘤(BL)的疗效及预后因素。本回顾性研究分析了2011年7月至2023年2月在血液病医院新诊断的30例BL患者的临床及生存数据。采用Kaplan-Meier法进行生存分析,对数秩检验用于预后因素的单因素分析。30例患者的中位年龄为43岁(24 - 66岁),男女比例为3:2。80%的患者存在结外侵犯,53.3%累及骨髓,10.0%累及中枢神经系统。Ann Arbor分期Ⅲ期和Ⅳ期的患者占86.7%。根据伯基特淋巴瘤国际预后指数(BL-IPI)危险因素数量,20.0%的患者为低危(0个),43.3%为中危(1个),36.7%为高危(≥2个)。所有患者均接受利妥昔单抗联合强化化疗的诱导方案治疗,客观缓解率和完全缓解率分别为80.0%和76.7%。中位随访时间为49个月(6 - 153个月),5年无进展生存(PFS)率和总生存(OS)率均为(76.7±7.7)%。所有局限期(=4)患者均实现持续完全缓解(CCR)。高危、晚期且诱导治疗敏感(=10)的患者序贯接受一线自体造血干细胞移植(auto-HSCT)作为巩固治疗;9例患者实现CCR,而1例中枢神经系统侵犯患者疾病早期进展并死亡。BL-IPI低危、中危和高危组的5年PFS率分别为(83.3±15.2)%、100.0%和(45.5±15.0)%(=0.0069),OS率分别为(83.3±15.2)%、100.0%和(45.5±15.0)%(=0.0075)。诱导治疗的主要不良反应为骨髓抑制和继发感染,通过适当的对症治疗可有效控制。单因素分析表明,PFS较差与BL-IPI评分≥2(=4.90,95% 1.02 - 23.45,=0.0329)、≥2个部位的结外侵犯(=12.62,95% 2.59 - 61.62,=0.0021)以及诱导治疗后未达到首次完全缓解(CR1)(=31.86,95% 4.19 - 242.20,<0.0001)相关。强化免疫化疗方案对高度侵袭性BL成年患者有效且耐受性良好。局限期疾病患者的治疗效果理想,而BL-IPI高危患者的预后不理想。序贯一线auto-HSCT巩固治疗可能进一步改善诱导治疗敏感的高危晚期疾病患者的预后。BL-IPI评分≥2、≥2个部位的结外侵犯以及诱导治疗后未达到CR1是成年BL患者的不良预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e16/11951218/8bb23fdc4585/cjh-46-02-134-g001.jpg

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