Current Status of Therapeutic Approaches to Adult T-Cell Leukemia

Abstract

More than 2 decades have elapsed since the proposal of adult T-cell leukemia (ATL). Since then, the discovery of the etiologic virus, human T-cell leukemia virus type I (HTLV-I), and the establishment of the diagnostic steps of serum test and molecular study have clearly defined ATL as a distinct disease entity. Because conventional chemotherapy, which is active against other lymphoid malignancies, was proven to be ineffective for treating aggressive forms of ATL, ATL has become the target of several clinical studies for the purpose of improving therapeutic outcomes. Combination chemotherapy exclusively designed for ATL has considerably elevated the treatment response rate in ATL patients, but it has not sufficiently extended the median survival time. The introduction of antiviral agents has led to surprising effects for patients with acute ATL. Monoclonal antibodies seem to be promising, especially for patients with chemotherapy-resistant disease. Unfortunately, these approaches did not prove to be sufficient for most patients with ATL to obtain long-term survival. Recent promising reports on allogeneic stem cell transplantation (allo-SCT) for ATL have suggested that allo-SCT could overcome the limitations that other treatment modalities have not surmounted. More efforts are clearly needed to clarify the usefulness of allo-SCT, especially with reduced-intensity conditioning regimens, for ATL patients.

Bone marrow transplantation from unrelated donors for patients with adult T-cell leukaemia/lymphoma

“…However, an HLA-identical sibling donor is not available for all patients suffering from ATLL, and only a few cases of allogeneic BMT from unrelated donors have been reported to date. 7,[13][14][15] Our hospital, Ehime Prefectural Central Hospital, is located in the Shikoku district of Japan, an area in which HTLV-1 infection is endemic. In 1999, we began performing unrelated BMT in patients with ATLL to improve the survival of patients with no available sibling donor.…”

Highly Enhanced Expression of CD70 on Human T-Lymphotropic Virus Type 1-Carrying T-Cell Lines and Adult T-Cell Leukemia Cells

“…Since conventional anticancer chemotherapy active against other lymphoid malignancies proved to be ineffective for treating aggressive types of ATL, combination chemotherapy designed exclusively for ATL has been examined. Although such chemotherapy considerably improved the treatment response rates in ATL patients, it could not sufficiently extend the median survival time (16,39). Therefore, it seems still mandatory to establish an effective strategy for the treatment of ATL.…”

Crystal structure of human T cell leukemia virus protease, a novel target for anticancer drug design

“…It is estimated that up to 30 million people worldwide are infected with HTLV, with ATL being particularly prevalent in Japan (3). Only an estimated 3-5% of people infected with the virus develop ATL in their lifetime, but for those that do, the prognosis is poor (4).…”

“…Only an estimated 3-5% of people infected with the virus develop ATL in their lifetime, but for those that do, the prognosis is poor (4). Although a number of treatments for ATL, such as combination chemotherapy, monoclonal antibodies directed against the ␣ chain of the interleukin 2 receptor, and antiviral therapy involving IFN-␣ and zidovudine, are used clinically, they show only very limited efficacy (3). Novel approaches under investigation use proteasome inhibitors (5) and Tax-targeted immunotherapy (4), but they have not yet been tested in practice.…”