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
Journal
Cancer Chemotherapy and Pharmacology
Journal Volume
68
Journal Issue
6
Pages
1387-1395
Date Issued
2011
Author(s)
Tzeng Y.-S.
Chen L.-T.
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. ? 2011 Springer-Verlag.
SDGs
Other Subjects
antibiotic agent; chlorambucil; cyclophosphamide; doxorubicin; etoposide; gemcitabine; immunoglobulin enhancer binding protein; prednisolone; rituximab; thalidomide; vincristine; adult; aged; API2 MALT1 fusion gene; article; B cell lymphoma; bone marrow; bone marrow relapse; cancer cell; cancer combination chemotherapy; cancer relapse; cancer staging; cancer tissue; CD3+ T lymphocyte; chromosome 11q; chromosome 18q; chromosome translocation 11; chromosome translocation 18; clinical article; down regulation; drug efficacy; drug response; eosinophil count; eradication therapy; event free survival; female; fusion gene; gene expression; Helicobacter infection; histopathology; human; human tissue; immunohistochemistry; inflammatory cell; lymphocytic infiltration; male; microvascular density; monotherapy; mucosa associated lymphoid tissue lymphoma; neutrophil; overall survival; priority journal; progression free survival; protein expression; reverse transcription polymerase chain reaction; salvage therapy; stomach lymphoma; tumor microenvironment; tumor vascularization; Aged; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 18; Disease-Free Survival; Female; Humans; Lymphoma, B-Cell, Marginal Zone; Male; Middle Aged; NF-kappa B; Oncogene Proteins, Fusion; Salvage Therapy; Stomach Neoplasms; Thalidomide; Translocation, Genetic
Type
journal article