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Overview of Targeted Therapies for Adult T-Cell Leukemia/Lymphoma

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Human T-Lymphotropic Viruses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1582))

Abstract

Adult T-Cell Leukemia/lymphoma (ATL) is the first human malignancy associated with a chronic infection by a retrovirus, the human T-cell lymphotropic virus type I (HTLV-I). ATL occurs, after a long latency period, only in about 5% of 10–20 millions infected individuals. ATL has a dismal prognosis with a median survival of less than 1 year, mainly due to its resistance to chemotherapy and to a profound immunosuppression. The viral oncoprotein, Tax, plays a major role in ATL oncogenic transformation by interfering with cell proliferation, cell cycle, apoptosis, and DNA repair. The diversity in ATL clinical features and prognosis led to Shimoyama classification of ATL into four clinical subtypes (acute, lymphoma, chronic, and smoldering) requiring different therapeutic strategies. Clinical trials, mainly conducted in Japan, demonstrated that combination of chemotherapy could induce acceptable response rate in the lymphoma subtype but not in acute ATL. However, long-term prognosis remains poor for both subtypes, due to a high relapse rate. Similarly, whether managed by a watchful waiting or treated with chemotherapy, the indolent forms (smoldering and chronic) have a poor long-term outcome. An international meta-analysis showed improved survival in the leukemic subtypes of ATL (chronic, smoldering as well as a subset of the acute subtype) with the use of two antiviral agents, zidovudine and interferon-alpha, and accordingly, this combination should be considered the standard first-line treatment in this context. ATL patients with lymphoma subtype benefit from induction chemotherapy, given simultaneously or sequentially with an antiviral combination of zidovudine and interferon-alpha. Allogeneic hematopoietic stem cells transplantation remains a promising and potentially curative approach but is limited to a small number of patients. Novel drugs such as arsenic trioxide in combination with interferon-alpha or monoclonal antibodies such as anti-CXCR4 have shown promising results and warrant further investigation.

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Author information

Authors and Affiliations

  1. Faculty of Medicine, Department of Anatomy, Cell Biology and Physiology, Americain University of Beirut, 113-6044, Beirut, Lebanon

    Rihab Nasr & Ali Bazarbachi M.D., Ph.D.

  2. Department of Hematology, Necker Hospital, University of Paris Descartes, 149, rue de Sèvres, Paris, France

    Ambroise Marçais & Olivier Hermine

  3. Faculty of Medicine, Department of Internal Medicine, American University of Beirut, 113-6044, Beirut, Lebanon

    Ali Bazarbachi M.D., Ph.D.

Authors
  1. Rihab Nasr
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  2. Ambroise Marçais
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  3. Olivier Hermine
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  4. Ali Bazarbachi M.D., Ph.D.
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Corresponding author

Correspondence to Ali Bazarbachi M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. University of Milano, Milano, Italy

    Claudio Casoli

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Nasr, R., Marçais, A., Hermine, O., Bazarbachi, A. (2017). Overview of Targeted Therapies for Adult T-Cell Leukemia/Lymphoma. In: Casoli, C. (eds) Human T-Lymphotropic Viruses. Methods in Molecular Biology, vol 1582. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6872-5_15

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  • DOI: https://doi.org/10.1007/978-1-4939-6872-5_15

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6870-1

  • Online ISBN: 978-1-4939-6872-5

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