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Progress in the management of ATL.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1), and its prognosis remains poor. Three to five percent of HTLV-1 carriers, infected mainly by breast feeding, develop ATL after a latency period as long as 70 years. The standard of care for aggressive ATL and indolent ATL comprises intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation, if applicable, and watchful waiting, respectively. Outside Japan, a combination of interferon-α and zidovudine has also been used as a therapeutic option for acute, chronic, and smoldering-type ATLs. A Japanese nationwide retrospective study revealed the outcome of patients diagnosed between 2000 and 2009. The median survival times were 8.3, 10.6, 31.5, and 55.0 months and the 4-year overall survival rates were 11%, 16%, 36%, and 52% for acute, lymphoma, chronic, and smoldering-type ATLs, respectively. Recently, the development of several novel agents has been attempted by targeting surface antigens on ATL cells such as CCR4 and CD30 with monoclonal antibodies, targeting molecular abnormalities in ATL cells with EZH1/2 inhibitor, and modulating the immune environment via immunomodulatory drugs (IMiDs) or immune checkpoint inhibitors. Among them, a CCR4 monoclonal antibody mogamulizumab, and an IMiD, lenalidomide, have been introduced for clinical use in Japan.

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