t(11;18)(q21;q21) 易位可作为边缘区 B 细胞淋巴瘤伴胃累及患者对挽救性沙利度胺治疗无反应的预测标志物。

t(11;18)(q21;q21) translocation as predictive marker for non-responsiveness to salvage thalidomide therapy in patients with marginal zone B-cell lymphoma with gastric involvement.

机构信息

Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Cancer Chemother Pharmacol. 2011 Dec;68(6):1387-95. doi: 10.1007/s00280-011-1631-y. Epub 2011 Apr 5.

DOI:10.1007/s00280-011-1631-y

PMID:21465313

Abstract

PURPOSE

Activation of TNF-α/NF-κB-related signaling pathway is crucial in sustain the growth of Helicobacter pylori-independent gastric mucosa-associated lymphoid tissue type (MALT) lymphoma. Thalidomide is an anti-angiogenic agent with anti-TNF-α and anti-NF-κB activity. This retrospective study evaluated the efficacy of thalidomide in standard therapy-failure gastric MALT lymphoma.

METHODS

Between October 2003 and September 2007, 10 patients with antibiotics-resistant, chemotherapy-refractory gastric MALT lymphoma who received salvage thalidomide therapy at daily doses of 100-200 mg were identified from medical records and included. Status of t(11;18)(q21;q21) was determined by reverse transcriptase polymerase chain reaction for API2-MALT1 transcript, while expression of NF-κB was detected by immunohistochemistry. Tumor response was evaluated by RECIST criteria.

RESULTS

Tumors were of stage IV in seven and IE/IIE-1 in three. The best tumor response after thalidomide was complete response in two and partial in three, with an overall response rate of 50% (95% confidence interval, 12.3-87.7%). At median follow-up of 39.3 months, the 3-year event-free and overall survival rates were 36.0% and 85.7%, respectively. API2-MALT1 transcript was detected in four (40%) tumors. Objective response rates of tumors with and without t(11;18)(q21;q21) were 0% (0/4) and 83% (5/6), respectively, P = 0.048 (Fisher's exact test). Thalidomide treatment was associated with significant down-regulation of nuclear NF-κB expression levels in residual neoplastic cells and microenvironments of responsive tumors, but not in t(11;18)(q21;q21)-positive, thalidomide-refractory tumors.

CONCLUSIONS

Thalidomide is an effective salvage treatment for standard therapy-failure, t(11;18)(q21;q21) translocation-negative gastric MALT lymphoma and deserves further exploration.

摘要

目的

TNF-α/NF-κB 相关信号通路的激活对于维持幽门螺杆菌独立的胃黏膜相关淋巴组织型（MALT）淋巴瘤的生长至关重要。沙利度胺是一种具有抗血管生成作用的抗 TNF-α 和抗 NF-κB 活性的药物。本回顾性研究评估了沙利度胺在标准治疗失败的胃 MALT 淋巴瘤中的疗效。

方法

本研究于 2003 年 10 月至 2007 年 9 月期间，从病历中确定了 10 例接受抗生素耐药、化疗耐药的胃 MALT 淋巴瘤患者，给予沙利度胺（每日 100-200mg）进行挽救治疗。通过逆转录酶聚合酶链反应确定 t(11;18)(q21;q21)的状态，通过免疫组织化学检测 NF-κB 的表达。根据 RECIST 标准评估肿瘤反应。

结果

7 例患者处于 IV 期，3 例处于 IE/IIE-1 期。沙利度胺治疗后肿瘤的最佳反应为完全缓解 2 例，部分缓解 3 例，总缓解率为 50%（95%置信区间，12.3-87.7%）。中位随访 39.3 个月时，3 年无事件生存率和总生存率分别为 36.0%和 85.7%。4 例（40%）肿瘤中检测到 API2-MALT1 转录本。有和无 t(11;18)(q21;q21)的肿瘤客观缓解率分别为 0%（0/4）和 83%（5/6），P=0.048（Fisher 确切检验）。沙利度胺治疗与反应性肿瘤残留肿瘤细胞和微环境中核 NF-κB 表达水平的显著下调相关，但与 t(11;18)(q21;q21)阳性、沙利度胺耐药的肿瘤无关。