Tsukasaki Kunihiro
Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.
Hematology. 2012 Apr;17 Suppl 1:S32-5. doi: 10.1179/102453312X13336169155330.
Adult T-cell leukemia-lymphoma (ATL) was first described in 1977 as a distinct clinico-pathological entity with a suspected viral etiology. Subsequently, a novel RNA retrovirus, human T-cell leukemia/lymphotropic virus type 1 (HTLV-1) was isolated from a cell line established from the leukemic cells of an ATL patient, and the finding of a clear association with ATL led to its inclusion among human carcinogenic pathogens. The three major routes of HTLV-1 transmission are mother-to-child infections via breast milk, sexual intercourse, and blood transfusions. HTLV-1 infection early in life, presumably from breast feeding, is crucial in the development of ATL. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into four categories, acute, lymphoma, chronic, and smoldering types defined by organ involvement, and LDH and calcium values. In cases of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL), intensive chemotherapy such as VCAP-AMP-VECP is usually recommended. In cases of favorable chronic or smoldering ATL (indolent ATL), watchful waiting until disease progression has been recommended although the long term prognosis was inferior to those of, for instance, chronic lymphoid leukemia. Retrospective analysis suggested that the combination of interferon alpha and zidovudine was apparently promising for the treatment of ATL, especially for types with leukemic manifestation. Allogeneic hematopoietic stem cell transplantation is also promising for the treatment of aggressive ATL possibly reflecting graft vs. ATL effect. Several new agent-trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody. Two steps should be considered for the prevention of HTLV-1-associated ATL. The first is the prevention of HTLV-1 infections and the second is the prevention of ATL among HTLV-1 carriers. So far, no agent has been found to be effective for the latter. Further investigation on the pathogenesis of ATL is crucial for the prevention and treatment of this refractory leukemia-lymphoma.
成人T细胞白血病-淋巴瘤（ATL）于1977年首次被描述为一种具有可疑病毒病因的独特临床病理实体。随后，从一名ATL患者白血病细胞建立的细胞系中分离出一种新型RNA逆转录病毒，即人类T细胞白血病/淋巴瘤病毒1型（HTLV-1），并且发现其与ATL存在明确关联，这使其被列入人类致癌病原体之中。HTLV-1传播的三大主要途径是通过母乳、性交和输血进行母婴感染。生命早期感染HTLV-1，大概是通过母乳喂养，对ATL的发展至关重要。该疾病患者临床特征和预后的多样性导致其被分为四类亚型，即急性、淋巴瘤、慢性和隐匿型，这些亚型由器官受累情况以及乳酸脱氢酶（LDH）和钙值来定义。对于急性、淋巴瘤或不良慢性亚型（侵袭性ATL）病例，通常推荐采用如VCAP-AMP-VECP等强化化疗。对于良性慢性或隐匿性ATL（惰性ATL）病例，尽管长期预后不如例如慢性淋巴细胞白血病，但建议密切观察直至疾病进展。回顾性分析表明，α干扰素和齐多夫定联合使用对于ATL的治疗显然很有前景，特别是对于有白血病表现的类型。异基因造血干细胞移植对于侵袭性ATL的治疗也很有前景，这可能反映了移植物抗ATL效应。目前正在进行和准备针对ATL的几种新药试验，包括一种去岩藻糖基化的人源化抗CC趋化因子受体4单克隆抗体。预防HTLV-1相关ATL应考虑两个步骤。第一步是预防HTLV-1感染，第二步是预防HTLV-1携带者发生ATL。到目前为止，尚未发现对后者有效的药物。进一步研究ATL的发病机制对于预防和治疗这种难治性白血病-淋巴瘤至关重要。
