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
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- Kuo, SH., Cheng, AL., Lin, CW. et al. Cancer Chemother Pharmacol (2011) 68: 1387. doi:10.1007/s00280-011-1631-y
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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.
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.
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.
Thalidomide is an effective salvage treatment for standard therapy-failure, t(11;18)(q21;q21) translocation-negative gastric MALT lymphoma and deserves further exploration.
KeywordsNF-κB Thalidomide Stomach API2-MALT1 MALT lymphoma
Mucosa-associated lymphoid tissue
Reverse transcriptase polymerase chain reaction