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利妥昔单抗体内净化干细胞自体移植序贯大剂量化疗治疗套细胞淋巴瘤的临床研究

[Clinical study of sequential high-dose chemotherapy with in vivo rituximab-purged stem cell autografting for mantle cell lymphoma].

作者信息

Takasaki Hirotaka, Hashimoto Chizuko, Takemura Sachiya, Motomura Shigeki, Ishigatsubo Yoshiaki

机构信息

Department of Chemotherapy, Kanagawa Cancer Center.

出版信息

Rinsho Ketsueki. 2010 Jan;51(1):57-62.

PMID:20134141
Abstract

Sequential high-dose chemotherapy with in vivo rituximab-purged stem cell autografting was designed for previously untreated mantle cell lymphoma (MCL). The response rate, disease-free survival (DFS), overall survival (OS) and toxicity were investigated in this trial. Between November 2001 and August 2008, five patients younger than 65 years of age with MCL at diagnosis were enrolled in this study. Initial chemotherapy consisted of 3 cycles of CHOP regimen followed by four courses of high-dose chemotherapy. During the in vivo purging phase, the patient was administered high-dose cyclophosphamide and cytarabine, and then each administration was followed by two infusions of rituximab. Molecular monitoring of minimal residual disease was performed by assessing DNA samples from bone marrow and autografted cells using PCR amplification of the bcl-1/IgH rearrangement. The complete response rate was 100%, and the 3-year OS and DFS were 100% and 100%, respectively. PCR analysis of autografted cells from four evaluable patients, 75% lymphoma-negative harvests were achieved following in vivo purging. One patient relapsed 3.2 years after treatment. The principal toxicity in the study was hematologic but there were no treatment-related deaths. Intensive high-dose sequential chemotherapy with in vivo purged stem cell support can achieve long-term disease-free survival for MCL.

摘要

序贯大剂量化疗联合体内利妥昔单抗清除的干细胞自体移植被设计用于既往未治疗的套细胞淋巴瘤(MCL)。本试验研究了缓解率、无病生存期(DFS)、总生存期(OS)及毒性。在2001年11月至2008年8月期间,5例诊断为MCL且年龄小于65岁的患者入组本研究。初始化疗包括3个周期的CHOP方案,随后进行4个疗程的大剂量化疗。在体内清除阶段,患者接受大剂量环磷酰胺和阿糖胞苷治疗,每次给药后接着输注两次利妥昔单抗。通过使用bcl-1/IgH重排的PCR扩增评估来自骨髓和自体移植细胞的DNA样本,对微小残留病进行分子监测。完全缓解率为100%,3年OS和DFS分别为100%和100%。对4例可评估患者的自体移植细胞进行PCR分析,体内清除后75%的收获物为淋巴瘤阴性。1例患者在治疗后3.2年复发。本研究中的主要毒性为血液学毒性,但无治疗相关死亡。强化大剂量序贯化疗联合体内清除的干细胞支持可使MCL患者获得长期无病生存。

相似文献

1
[Clinical study of sequential high-dose chemotherapy with in vivo rituximab-purged stem cell autografting for mantle cell lymphoma].利妥昔单抗体内净化干细胞自体移植序贯大剂量化疗治疗套细胞淋巴瘤的临床研究
Rinsho Ketsueki. 2010 Jan;51(1):57-62.
2
High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine.利妥昔单抗联合超CVAD与利妥昔单抗联合大剂量甲氨蝶呤和阿糖胞苷交替治疗新诊断的侵袭性套细胞淋巴瘤后持久缓解率高。
J Clin Oncol. 2005 Oct 1;23(28):7013-23. doi: 10.1200/JCO.2005.01.1825. Epub 2005 Sep 6.
3
High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients.大剂量阿糖胞苷联合放疗并进行自体移植挽救治疗R-CHOP方案敏感的套细胞淋巴瘤患者。
Br J Haematol. 2009 Feb;144(4):524-30. doi: 10.1111/j.1365-2141.2008.07498.x. Epub 2008 Nov 26.
4
Rituximab induces effective clearance of minimal residual disease in molecular relapses of mantle cell lymphoma.利妥昔单抗可有效清除套细胞淋巴瘤分子复发时的微小残留病灶。
Biol Blood Marrow Transplant. 2006 Dec;12(12):1270-6. doi: 10.1016/j.bbmt.2006.07.007.
5
[A patient with mantle cell lymphoma who successfully underwent auto-PBSCT in combination with in vivo purging of tumor cells using rituximab].一名套细胞淋巴瘤患者成功接受了自体外周血干细胞移植,并联合使用利妥昔单抗进行体内肿瘤细胞清除。
Gan To Kagaku Ryoho. 2002 Dec;29(13):2569-72.
6
The hyper-CVAD-rituximab chemotherapy programme followed by high-dose busulfan, melphalan and autologous stem cell transplantation produces excellent event-free survival in patients with previously untreated mantle cell lymphoma.采用高剂量白消安、美法仑及自体干细胞移植的超CVAD-利妥昔单抗化疗方案,可使既往未经治疗的套细胞淋巴瘤患者获得出色的无事件生存期。
Ann Hematol. 2007 Feb;86(2):101-5. doi: 10.1007/s00277-006-0193-2. Epub 2006 Nov 7.
7
Treatment of relapsed aggressive lymphomas: regimens with and without high-dose therapy and stem cell rescue.复发侵袭性淋巴瘤的治疗:含与不含高剂量治疗及干细胞救援的方案
Cancer Chemother Pharmacol. 2002 May;49 Suppl 1:S13-20. doi: 10.1007/s00280-002-0447-1. Epub 2002 Apr 12.
8
Rituximab: enhancing stem cell transplantation in mantle cell lymphoma.利妥昔单抗:增强套细胞淋巴瘤中的干细胞移植
Bone Marrow Transplant. 2002 Feb;29 Suppl 1:S10-3. doi: 10.1038/sj.bmt.1703296.
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Value of autologous stem cell transplantation with purged bone marrow as first-line therapy for follicular lymphoma with high tumor burden: a GOELAMS phase II study.以净化骨髓进行自体干细胞移植作为高肿瘤负荷滤泡性淋巴瘤一线治疗的价值:一项GOELAMS二期研究
Bone Marrow Transplant. 2000 Nov;26(9):971-7. doi: 10.1038/sj.bmt.1702631.
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Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).利妥昔单抗联合环磷酰胺、阿霉素、长春新碱及泼尼松进行免疫化疗可显著提高反应率并延长至治疗失败时间,但对既往未治疗的套细胞淋巴瘤患者的长期预后无改善:德国低度淋巴瘤研究组(GLSG)一项前瞻性随机试验的结果
J Clin Oncol. 2005 Mar 20;23(9):1984-92. doi: 10.1200/JCO.2005.08.133. Epub 2005 Jan 24.