Durable hematologic complete response and suppression of HTLV-1 viral load following alemtuzumab in zidovudine/IFN-{alpha}-refractory adult T-cell leukemia
| Autor: | Shannon Puhalla, Robert A. Baiocchi, John C. Byrd, Andrew P. Mone, Tamara Vukosavljevic, Amy Banks, Charles F. Eisenbeis, Susan P. Whitman, Julio Cruz, Michael A. Caligiuri, Pierluigi Porcu |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
CD52
Anti-HIV Agents Antibodies Neoplasm Clinical Trials and Observations medicine.medical_treatment viruses T-Lymphocytes Immunology T-cell leukemia Antineoplastic Agents Biology Antibodies Monoclonal Humanized Biochemistry immune system diseases Antigens CD Antigens Neoplasm hemic and lymphatic diseases medicine Humans Leukemia-Lymphoma Adult T-Cell Alemtuzumab Glycoproteins Human T-lymphotropic virus 1 Antibodies Monoclonal Interferon-alpha Cell Biology Hematology Immunotherapy Recovery of Function Middle Aged Viral Load medicine.disease Minimal residual disease Leukemia CD52 Antigen Female Tumor Suppressor Protein p53 Viral load Complete Hematologic Response Zidovudine medicine.drug |
| Zdroj: | Blood. 106(10) |
| ISSN: | 0006-4971 |
| Popis: | Adult T-cell leukemia (ATL) is a highly chemoresistant and usually fatal T-cell malignancy due to the human T-cell lymphotropic virus-1 (HTLV-1). After chemotherapy failure, antiretrovirals and interferon-α (IFN-α) produce brief responses followed by progression and death. More effective agents and new approaches to detect and treat minimal residual disease are needed. ATL cells express CD52, the target of the antibody alemtuzumab, which is active in a preclinical model of ATL and is cytotoxic for p53-deficient cells. A patient with refractory chronic ATL in transformation achieved longer than a 1-year complete hematologic response following 12 weeks of outpatient subcutaneous alemtuzumab. Persistent suppression of HTLV-1 viral load, even at recovery of T cells, after alemtuzumab and efficient in vitro complement-mediated cytotoxicity of primary ATL cells with mutated TP53 were observed. The unprecedented response and the profound suppression of HTLV-1 viral load observed in this patient suggest that further clinical investigation of alemtuzumab in ATL is warranted. |
| Databáze: | OpenAIRE |
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