The Combination Of Arsenic, Interferon-Alpha, and Zidovudine Restores An 'Immunocompetent-like' Micro-Environment In Patients With Adult T-Cell Leukemia/Lymphoma
| Autor: | Ghada Kchour, S. A. Rahim Rezaee, Reza Farid, Akram Ghantous, Houshang Rafatpana, Mahdi Tarhini, Mohamad-Mehdi Kooshyar, Hiba El Hajj, Fadwa Berry, Roudaina Nasser, Abbas Shirdel, Zeina Dassouki, Mohamad Ezzedine, Hossein Rahimi, Ardeshir Ghavamzadeh, Hugues de Thé, Olivier Hermine, Mahmoud Mahmoudi, Ali Bazarbachi |
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| Rok vydání: | 2013 |
| Předmět: |
biology
business.industry Immunology T-cell leukemia Cell Biology Hematology medicine.disease biology.organism_classification Biochemistry Adult T-cell leukemia/lymphoma chemistry.chemical_compound Leukemia Zidovudine chemistry Aldesleukin Human T-lymphotropic virus 1 Medicine IL-2 receptor Arsenic trioxide business medicine.drug |
| Zdroj: | Blood. 122:5100-5100 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v122.21.5100.5100 |
| Popis: | Background HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. Methods Here we assessed Th1/Th2/Treg cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. Results ATL patients at diagnosis displayed a Treg/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4+CD25+ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4+CD25+ cells. Conclusions The observed shift from a Treg/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections. Disclosures: Off Label Use: Off label use of arsenic trioxide, zidovudine and interferon-alpha for the treatment of adult T cell leukemia/lymphoma. |
| Databáze: | OpenAIRE |
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