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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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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.

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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

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Acknowledgments

This study was supported by research grants NSC98-2314-B-002-087MY3, and NSC99-2627-B-002-008 from the National Science Council, Taiwan, DOH96-DT-B-111-001 from Department of Health, Taiwan, and NTUH. 98-S1130 from National Taiwan University Hospital, Taiwan.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

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

    Sung-Hsin Kuo, Ann-Lii Cheng, Chih-Hung Hsu, Kun-Huei Yeh & Yi-Shin Tzeng

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

    Sung-Hsin Kuo, Ann-Lii Cheng & Ming-Shiang Wu

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

    Chung-Wu Lin

  4. Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan

    Sung-Hsin Kuo, Ann-Lii Cheng, Chih-Hung Hsu, Kun-Huei Yeh & Yi-Shin Tzeng

  5. National Institute of Cancer Research, National Health Research Institutes, 2F. No. 36, Sheng-Li Rd, Tainan, 70456, Taiwan

    Ann-Lii Cheng & Li-Tzong Chen

  6. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Li-Tzong Chen

  7. Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan

    Li-Tzong Chen

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  1. Sung-Hsin Kuo
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Correspondence to Li-Tzong Chen.

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Kuo, SH., Cheng, AL., Lin, CW. et al. 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. Cancer Chemother Pharmacol 68, 1387–1395 (2011). https://doi.org/10.1007/s00280-011-1631-y

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  • DOI: https://doi.org/10.1007/s00280-011-1631-y

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