Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 6, pp 1387–1395

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

  • Sung-Hsin Kuo
  • Ann-Lii Cheng
  • Chung-Wu Lin
  • Chih-Hung Hsu
  • Ming-Shiang Wu
  • Kun-Huei Yeh
  • Yi-Shin Tzeng
  • Li-Tzong Chen
Original Article

DOI: 10.1007/s00280-011-1631-y

Cite this article as:
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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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.

Keywords

NF-κB Thalidomide Stomach API2-MALT1 MALT lymphoma 

Abbreviations

MALT

Mucosa-associated lymphoid tissue

RT-PCR

Reverse transcriptase polymerase chain reaction

CR

Complete remission

PR

Partial remission

SD

Stable disease

PD

Disease progression

MVD

Microvascular density

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sung-Hsin Kuo
    • 1
    • 2
    • 4
  • Ann-Lii Cheng
    • 1
    • 2
    • 4
    • 5
  • Chung-Wu Lin
    • 3
  • Chih-Hung Hsu
    • 1
    • 4
  • Ming-Shiang Wu
    • 2
  • Kun-Huei Yeh
    • 1
    • 4
  • Yi-Shin Tzeng
    • 1
    • 4
  • Li-Tzong Chen
    • 5
    • 6
    • 7
  1. 1.Department of OncologyNational Taiwan University Hospital and National Taiwan University College of MedicineTaipeiTaiwan
  2. 2.Department of Internal MedicineNational Taiwan University Hospital and National Taiwan University College of MedicineTaipeiTaiwan
  3. 3.Department of PathologyNational Taiwan University Hospital and National Taiwan University College of MedicineTaipeiTaiwan
  4. 4.Cancer Research CenterNational Taiwan University College of MedicineTaipeiTaiwan
  5. 5.National Institute of Cancer Research, National Health Research InstitutesTainanTaiwan
  6. 6.Department of Internal Medicine, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
  7. 7.Department of Internal MedicineNational Cheng-Kung University HospitalTainanTaiwan

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