國家衛生研究院 NHRI:Item 3990099045/5071

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Title:	Helicobacter pylori-independent MALT lymphoma patients responsive to thalidomide-the molecular mechanism and the clinical application
Authors:	Kuo, S;Chen, L;Wu, M;Hsu, C;Lin, C;Hsu, P;Yeh, K;Tzeng, Y;Cheng, A
Contributors:	National Institute of Cancer Research
Abstract:	Background: We have recently demonstrated that nuclear expression of BCL10 or NF-{kappa}B helps predict H. pylori-independent status; and inflammatory cytokines such as TNF-{alpha} may be related to BCL10 nuclear translocation (Blood 2005;106:1037–41;J Biol Chem 2006;281:167–75). Recent studies have been shown that the chimeric protein of t(11;18)(q21;q21) can lead to constitutive NF-{kappa}B activity and thereby mediate cell survival and anti-apoptotic signals. The present study was conducted to investigate the molecular mechanism and the clinical efficacy of thalidomide, an TNF-{alpha} or NF-{kappa}B inhibitor, in H. pylori-independent MALT lymphoma. Methods: Between October 2003 and June 2007, our study enrolled 11 H. pylori-independent MALT lymphoma patients ( 7 men and 4 women; age range, 43 to 79 years; 7 patients who had failed chemotherapy or rituximab) with nuclear expression of BCL10 or NF-{kappa}B in pretreatment lymphoma tissues treated at National Taiwan University Hospital with thalidomide 100mg to 200 mg oral given daily. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript. Results: Three (27.3%) of 11 patients achieved a complete response (CR), and 3 (27.3) of 11 patients achieved a partial response (PR), resulting in an overall response rate of 54.5% (95% CI, 19.5%-89.6%). The median time from thalidomide therapy to CR was 3.0 months (range, 2.7–4.9 months). At a median follow-up of 41.6 months (range, 17.7–63.8 months), the 3-year event-free survival and overall survival after thalidomide treatment was 80.8%, and 88.9%, respectively. The API2-MALT1 fusion transcript for t(11;18)(q21;q21) was detected in 1 (16.7%) of 6 patients with CR or PR, and 4 (80.0%) of 5 patients with stable or progressive disease (P = 0.08). Conclusions: Our results indicate that thalidomide can be an adjuvant treatment for H. pylori-independent MALT lymphoma patients. Additional investigation of the molecular mechanisms and biologic significance of the API2-MALT1 fusion transcript responsible for thalidomide resistance in this group of tumors is needed.
Date:	2009-05-20
Relation:	Journal of Clinical Oncology. 2009 May 20;27(15s):Abstract number e19512.
Link to:	http://meeting.ascopubs.org/cgi/content/abstract/27/15S/e19512
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0732-183X&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000276606605525
Appears in Collections:	[Li-Tzong Chen] Conference Papers/Meeting Abstract

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