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利妥昔单抗作为 BEAM 预处理方案的辅助治疗用于霍奇金淋巴瘤的自体造血干细胞移植。

Rituximab as adjunctive therapy to BEAM conditioning for autologous stem cell transplantation in Hodgkin lymphoma.

机构信息

Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.

Department of Medicine, Houston Methodist Hospital, Houston, TX, USA.

出版信息

Bone Marrow Transplant. 2022 Apr;57(4):579-585. doi: 10.1038/s41409-022-01599-5. Epub 2022 Feb 1.

DOI:10.1038/s41409-022-01599-5
PMID:35105965
Abstract

While high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) leads to improved disease-free survival (DFS) for children and adults with relapsed/refractory Hodgkin lymphoma (HL), relapse remains the most frequent cause of mortality post-transplant. Rituximab has been successfully incorporated into regimens for other B-cell lymphomas, yet there have been limited studies of rituximab in HL patients. We hypothesized that adding rituximab to BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning would reduce relapse risk in HL patients post-transplant. Here, we retrospectively review the outcomes of patients with relapsed/refractory HL who received rituximab in addition to BEAM. The primary outcome was DFS. Our cohort included 96 patients with a median age of 28 years (range, 6-76). Majority of patients (57%) were diagnosed with advanced (Stage III-IV) disease, and 62% were PET negative pre-transplant. DFS was 91.5% at 1 year [95% CI 86-98%], and 78% at 3 years [95% CI 68-88%]. NRM was 0% and 3.5% at 1-year [95% CI 0-3%] and 3-years [95% CI 0-8.5%], respectively. 25% of patients developed delayed neutropenia, with 7% requiring infection-related hospitalizations, and one death. We have demonstrated excellent outcomes for patients receiving rituximab with BEAM conditioning for relapsed/refractory HL. Future comparative studies are needed to better determine whether rituximab augments outcomes post-transplant.

摘要

虽然高剂量化疗联合自体造血干细胞移植(ASCT)可改善复发/难治性霍奇金淋巴瘤(HL)患儿和成人的无病生存(DFS),但移植后复发仍是最常见的死亡原因。利妥昔单抗已成功纳入其他 B 细胞淋巴瘤的治疗方案,但在 HL 患者中的研究有限。我们假设在 BEAM(卡莫司汀、依托泊苷、阿糖胞苷、美法仑)预处理方案中添加利妥昔单抗可降低 HL 患者移植后的复发风险。在此,我们回顾性分析了接受利妥昔单抗联合 BEAM 治疗的复发/难治性 HL 患者的结局。主要结局是 DFS。我们的队列包括 96 例中位年龄为 28 岁(范围:6-76 岁)的患者。大多数患者(57%)患有晚期(III-IV 期)疾病,62%的患者在移植前 PET 阴性。1 年时 DFS 为 91.5%[95%CI 86-98%],3 年时为 78%[95%CI 68-88%]。1 年时 NRM 为 0%和 3.5%[95%CI 0-3%]和 3 年时[95%CI 0-8.5%],分别。25%的患者发生迟发性中性粒细胞减少症,其中 7%需要与感染相关的住院治疗,1 例死亡。我们已经证明了接受利妥昔单抗联合 BEAM 预处理治疗复发/难治性 HL 的患者的良好结局。需要进一步的比较研究来更好地确定利妥昔单抗是否可提高移植后的疗效。

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本文引用的文献

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Rituximab and obinutuzumab differentially hijack the B cell receptor and NOTCH1 signaling pathways.利妥昔单抗和奥滨尤妥珠单抗对B细胞受体和NOTCH1信号通路的劫持作用存在差异。
iScience. 2021 Jan 22;24(2):102089. doi: 10.1016/j.isci.2021.102089. eCollection 2021 Feb 19.
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Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults.利妥昔单抗在儿童、青少年和青年中的使用与不良事件的关系。
JAMA Netw Open. 2021 Feb 1;4(2):e2036321. doi: 10.1001/jamanetworkopen.2020.36321.
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T-Cell Therapy for Lymphoma Using Nonengineered Multiantigen-Targeted T Cells Is Safe and Produces Durable Clinical Effects.
利用未经基因工程改造的多抗原靶向 T 细胞进行淋巴瘤的 T 细胞疗法是安全的,并产生持久的临床效果。
J Clin Oncol. 2021 May 1;39(13):1415-1425. doi: 10.1200/JCO.20.02224. Epub 2021 Jan 28.
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Brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine in patients with advanced-stage, classical Hodgkin lymphoma: A prespecified subgroup analysis of high-risk patients from the ECHELON-1 study.本妥昔单抗维布妥昔单抗联合多柔比星、长春碱和达卡巴嗪治疗晚期经典型霍奇金淋巴瘤患者:来自 ECHELON-1 研究高危患者的预设亚组分析。
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Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison.帕博利珠单抗对比在接受维布妥昔单抗治疗后进展的复发难治性经典型霍奇金淋巴瘤的标准治疗:一项间接治疗比较
Expert Rev Hematol. 2018 Jun;11(6):503-511. doi: 10.1080/17474086.2018.1475226. Epub 2018 May 23.