Abstract
Adult T-cell leukemia-lymphoma (ATL) is a distinct mature T-cell malignancy caused by human T-cell leukemia/lymphotropic virus type I (HTLV-1) endemic in some areas in the world. HTLV-1 transmits through mother-to-child infection via breastfeeding, sexual intercourses, and blood transfusions. Early HTLV-1 infection, presumably through mother’s milk, is crucial in developing ATL. The estimated cumulative risk of the development of ATL in HTLV-1 carriers is a few percent after transmission from their mothers. The median age of ATL onset is about 70 in Japan and is now rising, whereas an overall mean age in the mid-forties is reported in other parts of the world. ATL is classified into four clinical subtypes (acute, lymphoma, chronic, and smoldering) defined by organ lesions and LDH/calcium values. In aggressive ATL (acute, lymphoma or unfavorable chronic types) and indolent ATL (favorable chronic or smoldering types), intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation and watchful waiting until disease progression has been recommended, respectively, in Japan. Based on a worldwide meta-analysis and multiple other retrospective studies, the antiviral combination of interferon alpha (IFN) and zidovudine (AZT) is recommended in many parts of the world in acute, chronic, and smoldering ATL whereas patients with the lymphoma subtype are treated with chemotherapy, either alone or combined with AZT/IFN. Several new agents have been approved for ATL by the Pharmaceutical and Medical Devices Agency (PMDA) after clinical trials, including an anti-CC chemokine receptor 4 monoclonal antibody, mogamulizumab; an immunomodulatory agent, lenalidomide; and an anti-CD30 antibody/drug conjugate, brentuximab vedotin.
Highlights
Approaches and Established Treatments for Adult T Cell LeukemiaAdult T-cell leukemia-lymphoma (ATL) is a distinct mature T-cell malignancy caused by human T-cell leukemia/lymphotropic virus type I (HTLV-1) endemic in some areas in the world
Since reverse transcriptase-mediated viral replication does not occur in the malignant cells, these results highly suggest that the primary target of the AZT/IFN combination is the Adult T-cell leukemia–lymphoma (ATL) microenvironment, de novo infection of T cells by HTLV-1 which appears critical for the survival of the malignant clone
These findings led to the conclusion that mLSG15 is more effective than CHOP-14 and led to improved 3-year overall survival (OS) and CR rate, but this was at the expense of higher toxicity, prompting further research for the treatment of aggressive ATL whose prognosis is still poor as compared to other hematological malignancies
Summary
Adult T-cell leukemia-lymphoma (ATL) is a distinct mature T-cell malignancy caused by human T-cell leukemia/lymphotropic virus type I (HTLV-1) endemic in some areas in the world. HTLV-1 infection, presumably through mother’s milk, is crucial in developing ATL. The estimated cumulative risk of the development of ATL in HTLV-1 carriers is a few percent after transmission from their mothers. The median age of ATL onset is about 70 in Japan and is rising, whereas an overall mean age in the mid-forties is reported in other parts of the world. ATL is classified into four clinical subtypes (acute, lymphoma, chronic, and smoldering) defined by organ lesions and LDH/calcium values. Based on a worldwide meta-analysis and multiple other retrospective studies, the antiviral combination of interferon alpha (IFN) and zidovudine (AZT) is recommended in many parts of the world in acute, chronic, and smoldering ATL whereas patients with the lymphoma subtype are treated with chemotherapy, either alone or combined with AZT/IFN.
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