自体造血干细胞移植联合利妥昔单抗治疗非霍奇金淋巴瘤6例

doi:10.3969/j.issn.1673-8225.2010.06.040

摘要/Abstract

摘要：

背景：利妥昔单抗单用或联合CHOP方案化疗治疗CD20阳性非霍奇金淋巴瘤已取得较好疗效，非霍奇金淋巴瘤经自体造血干细胞移植治疗同样可以提高患者的疗效和生存率，而将两种方法联合的效果尚存在争论。

目的：探讨自体造血干细胞移植联合利妥昔单抗对CD20阳性非霍奇金淋巴瘤的有效性。

方法：对6例CD20阳性非霍奇金淋巴瘤Ⅳ期患者进行自体造血干细胞移植的同时，联合使用利妥昔单抗，分别于移植前给予2~4次，动员和预处理前后各2次，移植后每3个月维持治疗1次，利妥昔单抗用量为 375 mg/m²静滴。

结果与结论：平均采集单个核细胞数为5.13× 10^-8/kg，CD34⁺细胞数为4.75×10^-6/kg。6例患者自体造血干细胞移植后，造血功能均恢复顺利，中性粒细胞计数大于0.5×10^-9L^-1为移植后9~15 d，血小板计数大于20×10^-9L^-1为移植后12~19 d。6例患者在移植过程中均未发生出血性膀胱炎、间质性肺炎、巨细胞病毒感染和肝静脉阻塞等并发症。利妥昔单抗使用过程中，无发热、寒战、皮疹等不良反应发生。移植后6~32个月，患者均处于完全缓解状态。提示自体造血干细胞移植并利妥昔单抗治疗CD20阳性非霍奇金淋巴瘤是一种较好的方法，可维持治疗效果，有利于防止复发。

关键词: 非霍奇金淋巴瘤, 利妥昔, 化疗, 移植, 自体造血干细胞, 干细胞

Abstract:

BACKGROUND: Rituximab single or in combination with CHOP regimen for treatment of CD20-positive non-Hodgkin lymphoma has achieved good curative effects. Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve the curative effects and increase survival rate of patients with non-Hodgkin lymphoma. However, the curative effects of these two methods remain disputed.
OBJECTIVE: To investigate the efficiency of rituximab in combination with AHSCT on CD 20-positive non-Hodgkin lymphoma.
METHODS: Six patients with CD 20-positive non-Hodgkin lymphoma (stage IV) underwent AHSCT and rituximab administration. 375 mg/m² rituximab was intravenously administered 2-4 times prior to AHSCT, twice prior to and after peripheral blood stem cells mobilization and preprocessing, respectively, as well as once every 3 months after AHSCT.
RESULTS AND CONCLUSION: The mean number of mononuclear cells and CD 34-positive cells was 5.13×10^-8/kg and 4.75×10^-6/kg, respectively. Following AHSCT, all 6 patients presented normal hematopoietic functions, neutrophils exceeded 0.5×10^-9/L at 9-15 days and blood platelet counts exceeded 20×10^-9/L at 12-19 days. Hemorrhagic cystitis, interstitial pneumonia, cytomegalovirus infection, or hepatic venous obstruction was not observed during the whole process of AHSCT in each patient. At 6-32 months, patients completely recovered. These results indicate that rituximab in combination with AHSCT is a good method for treatment of CD20-positive non-Hodgkin lymphoma and rituximab maintenance therapy could prevent disease recurrence.

中图分类号:

R394.2

孙志强，王季石，卢英豪，谢润兰，龙正美. 自体造血干细胞移植联合利妥昔单抗治疗非霍奇金淋巴瘤6例[J]. 中国组织工程研究, 2010, 14(6): 1138-1140.

Sun Zhi-qiang, Wang Ji-shi, Lu Ying-hao, Xie Run-lan, Long Zheng-mei. Rituximab combined with autologous hematopoietic stem cell transplantation for treatment of non-Hodgkin lymphoma in 6 patients[J]. Chinese Journal of Tissue Engineering Research, 2010, 14(6): 1138-1140.

参考文献

引言

材料方法

讨论

AHSCT has been widely accepted in the treatment of relapsed or refractory invasive lymphoma. Considerable studies support a viewpoint that autologous transplantation can be used as a standard treatment, in particular for the patients with relapsed lymphoma who are sensitive to chemotherapy. Evidence exists that AHSCT, as a first-choice therapeutic intervention, can reduce 40%-50% of tumor invasion, and 18%-25% of patients with relapsed lymphoma receive the second complete remission. Compared with conventional treatment, AHSCT increases long-term survival rate over 30%, enhances the curative effects of non-Hodgkin lymphoma, reduces relapse, and prolongs healthy survival period^[2-3]. But AHSCT as a first-choice method for treatment of high-risk, invasive lymphoma remains disputed. Greb et al^[4] performed a meta analysis of 2 728 patients with invasive non-Hodgkin lymphoma and concluded no difference between AHSCT and conventional therapeutic methods in terms of non-reduced survival rate and total survival rate. This occurs because 40%-70% of non-Hodgkin lymphoma patients unavoidably suffer from relapsed lymphoma and die following AHSCT, and relapsed lymphoma is frequently observed in patients who present with tiny residual disease foci in vivo and/or receive tumor cells contaminated AHSCT. Rituximab, a chimeric murine/human monoclonal antibody, kills tumor cells by antibody-dependent cells mediated cytotoxicity, complement-dependent cytoxic effect, inducing tumor cell apoptosis, interfering anti-apoptotic approach, and increasing lymphoma cell sensitivity to chemotherapy^[5]. Rituximab combined with chemotherapy has been widely used to treat CD20-positive non-Hodgkin lymphoma and acquire satisfactory curative efficacy. Rituximab in conjunction with AHSCT for treatment of CD20-positive non-Hodgkin lymphoma has recently become a rapidly growing area of research. Several studies^[6-7] have demonstrated that rituximab chemotherapy combined with AHSCT for treatment of progressive non-Hodgkin lymphoma can acquire satisfactory healthy survival rate and long-term survival rate. Umberto et al^[8] recently reported that rituximab chemotherapy plus AHSCT for treatment of progressive non-Hodgkin lymphoma had acquired 70% 4-year healthy survival rate, and 80% 4-year total survival rate, and the control results are 44% and 54% respectively. Michele et al^[9] used intensive chemotherapy, rituximab infusion, and AHSCT to treat 15 patients with CD20-positive mantle cell or follicular lymphoma and acquired good therapeutic efficacy. The negative-tutnning rate of IgH gene rearrangements was 93% and at 14 months after AHSCT, 93% of patients were still in complete remission. Christian et al^[10] reported similar results. The present study used rituximab infusion and AHSCT to treat 6 patients with CD 20-positive non-Hodgkin lymphoma and obtained good short-term curative effects. These results indicate that rituximab combined with AHSCT is presently an ideal choice for treatment of CD20-positive lymphoma. Rituximab infusion in combination with chemotherapy mobilization and in vivo purging has been studied. For example, Michele et al^[9] reported 15 patients with lymphoma invovling bone marrow and received anti-CD20 monoclonal antibody rituximab. Results revealed that the CD34-positive cells harvested from the patients who received both chemotherapy and rituximab were polymerase chain reaction-negative in 93% of cases (versus 40% of controls). Belhadj et al^[11] treated 11 relapsed B cell non-Hodgkin lymphoma first with rituximab, then a mobilization chemotherapeutic regimen, followed by peripheral blood stem cell transplantation. Results revealed that harvests were free of PCR-detectable molecular marker in 9 cases. There is evidence that following in vitro purging with rituximab, 80%-90% of stem cell harvests from patients with PCR-negative peripheral blood were contaminated with lymphoma cells^[9], which presumes not to produce influences on mobilization and collection of peripheral blood stem cells, although related laboratory examinations are not performed. Brugger et al^[12] reported that rituximab consolidation after AHSCT can prevent repalse by clearance of minimal residual disease in patients with follicular or mantle cell lymphoma. The present study used rituximab (375 mg/m², i.v.) once every 3 months for 1-2 years in succession to prevent relapse as far as possible. During the whole follow-up period, all patients were in complete remission, with marked curative effect. But long-term curative efficacy needs to be further investigated. In addition, whether rituximab can inhibit organism’s immune function, increase function is also the key part in future work.

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