Nasr Rihab, Marçais Ambroise, Hermine Olivier, Bazarbachi Ali
Faculty of Medicine, Department of Anatomy, Cell Biology and Physiology, Americain University of Beirut, 113-6044, Beirut, Lebanon.
Department of Hematology, Necker Hospital, University of Paris Descartes, 149, rue de Sèvres, Paris, France.
Methods Mol Biol. 2017;1582:197-216. doi: 10.1007/978-1-4939-6872-5_15.
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.
成人T细胞白血病/淋巴瘤（ATL）是首例与逆转录病毒——人类嗜T细胞病毒I型（HTLV-I）慢性感染相关的人类恶性肿瘤。经过漫长的潜伏期后，ATL仅在1000万至2000万受感染个体中的约5%中发生。ATL预后不佳，中位生存期不到1年，主要原因是其对化疗耐药以及严重的免疫抑制。病毒癌蛋白Tax通过干扰细胞增殖、细胞周期、细胞凋亡和DNA修复，在ATL致癌转化中起主要作用。ATL临床特征和预后的多样性导致Shimoyama将ATL分为四种临床亚型（急性、淋巴瘤、慢性和冒烟型），需要不同的治疗策略。主要在日本进行的临床试验表明，化疗联合应用可在淋巴瘤亚型中诱导出可接受的缓解率，但在急性ATL中则不然。然而，由于复发率高，这两种亚型的长期预后仍然很差。同样，无论是采用观察等待还是化疗，惰性形式（冒烟型和慢性型）的长期预后都很差。一项国际荟萃分析显示，使用两种抗病毒药物齐多夫定和α干扰素，ATL白血病亚型（慢性、冒烟型以及急性亚型的一个子集）的生存率有所提高，因此，在这种情况下，这种联合治疗应被视为标准的一线治疗方法。淋巴瘤亚型的ATL患者可从诱导化疗中获益，诱导化疗可与齐多夫定和α干扰素的抗病毒联合治疗同时或序贯进行。异基因造血干细胞移植仍然是一种有前景且可能治愈的方法，但仅限于少数患者。新型药物如三氧化二砷与α干扰素联合使用，或单克隆抗体如抗CXCR4已显示出有前景的结果，值得进一步研究。
