Focus on treatment of HTLV-I-associated adult T-cell Leukemia/Lymphoma

Abstract

Adult T Leukemia/lymphoma (ATL) is the first human malignancy associated with chronic infection by the HTLV-1 retrovirus. ATL occurs after a long latency period only in about 5% of 10 to 20 million infected people. ATL carries a very bad prognosis because of intrinsic chemo-resistance and severe immunosuppression. The viral oncoprotein Tax is an important player in the etiology of ATL and acts by interfering with cell proliferation, cell cycle, apoptosis and DNA repair. Shimoyama classification describes four clinical forms of ATL (acute, chronic, lymphoma, and smoldering). In the aggressive forms (acute and lymphoma ATL), clinical trials mainly conducted in Japan showed that combinations of chemotherapy can induce acceptable response rate in ATL lymphoma but not in the acute form. However, due to a high relapse rate in both cases, long-term prognosis remains poor. Similarly, the so-called indolent forms (smoldering and chronic ATL) have a bad long-term prognosis whether they are managed with a watchful waiting policy or with chemotherapy. Recently, we conducted a worldwide meta-analysis that revealed that the combination of zidovudine and interferon-alpha is highly effective in the leukemic forms of ATL and should be considered as standard first line therapy in that setting. This combination has changed the natural history of the disease and induced a significant improvement in long-term survival of patients with chronic or smoldering ATL as well as in a subset of patients with acute ATL. Patients with the lymphoma form still benefit from chemotherapy induction with concurrent or sequential antiretroviral therapy with zidovudine/IFN. Allogeneic bone marrow transplantation remains a promising and potentially curative way for a small number of patients. New medications such as arsenic trioxide combined with interferon alpha or monoclonal antibodies such as anti-CXCR4, have shown promising results.