ATL is a distinct peripheral T-lymphocytic malignancy associated with human T-cell lymphotropic virus type I (HTLV-1). 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 case of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL), intensive chemotherapy like the LSG15 regimen (VCAP-AMP-VECP) is usually recommended if outside of clinical trials, based on the results of a phase 3 trial. In case 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 (allo-HSCT) is also promising for the treatment of aggressive ATL possibly reflecting graft versus ATL effect. Several new agent trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody, IL2-fused with diphtheria toxin, histone deacetylase inhibitors, a purine nucleoside phosphorylase inhibitor, a proteasome inhibitor, and lenalidomide. 1. Introduction Adult T-cell leukemia-lymphoma (ATL) was first described in 1977 by Uchiyama et al. as a distinct clinico-pathological entity with a suspected viral etiology because of the clustering of the disease in the southwest region of Japan [1]. Subsequently, a novel RNA retrovirus, human T-cell leukemia/lymphotropic virus type I (HTLV-1), was isolated from a cell line established from leukemic cells of an ATL patient, and the finding of a clear association with ATL led to its inclusion among human carcinogenic pathogens [2–5]. In the mid-1980s and 1990s, several inflammatory diseases were reported to be associated with HTLV-1 [6–10]. At the same time, endemic areas for the virus and diseases have been found (reviewed in [11–13]). Diversity in ATL has been recognized and a classification of clinical subtypes of the disease was proposed [14]. This chapter will review the current recognition of ATL focusing on treatment of the disease. 2. Clinical Features and Laboratory Findings of ATL ATL patients show a variety of clinical manifestations because of various complications of organ involvement
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