title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Hsin
authors.initials: SH
authors.lastname: Kuo
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Chung-Wu
authors.initials: CW
authors.lastname: Lin
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
authors.forename: Kun-Huei
authors.initials: KH
authors.lastname: Yeh
authors.forename: Yi-Shin
authors.initials: YS
authors.lastname: Tzeng
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
mesh_terms: D000368:Aged; D002880:Chromosomes, Human, Pair 11; D002887:Chromosomes, Human, Pair 18; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016879:Salvage Therapy; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D013792:Thalidomide / Q000627:therapeutic use*; D014178:Translocation, Genetic
chemical_list: C415943:API2-MALT1 fusion protein, human; D016328:NF-kappa B; D015514:Oncogene Proteins, Fusion; D013792:Thalidomide